Advances in Carbohydrate Chemistry and Biochemistry, Volume 53

Advances in Carbohydrate Chemistry and Biochemistry

Volume 53

This Page Intentionally Left Blank

Advances in Carbohydrate Chemistry and Biochemistry Editor DEREK HORTON The American University Washington, DC

Board of Advisors LAURENS ANDERSON DAVIDR. BUNDLE STEPHEN J. ANGYAL STEPHEN HANESSIAN BENGT LINDBERG HANSH. BAER CLINTON E. BALLOU HANSPAULSEN NATHANSHARON JOHNS. BRIMACOMBE J. F. G. VLIEGENTHART J. GRANT BUCHANAN ROYL. WHISTLER

Volume 53

ACADEMIC PRESS San Diego London Boston New York Sydney Tokyo Toronto

This book is printed on acid-free paper. @ Copyright 0 1998 by ACADEMIC PRESS All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the Publisher. The appearance of the code at the bottom of the first page of a chapter in this book indicates the Publisher’s consent that copies of the chapter may be made for personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per copy fee through the Copyright Clearance Center, Inc. (222 Rosewood Drive, Danvers, Massachusetts 01923), for copying beyond that permitted by Sections 107 or 108 of the US.Copyright Law. This consent does not extend to other kinds of copying, such as copying for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale. Copy fees for pre-1998 chapters are as shown on the title pages. If no fee code appears on the title page, the copy fee is the same as for current chapters. 0065-23 18/98 $25.00

Academic Press a division of Harcourt Brace & Company

525 B Street, Suite 1900, San Diego, California 921014495. USA http:llwww.apnet.com Academic Press Limited 24-28 Oval Road, London NWI 7DX, UK http://www.hbuk.co.uk/ap/ International Standard Book Number: 0-12-007253-X

PRINTED IN THE IJNITEDSTATES OF AMERICA 98 9 9 0 0 01 02 0 3 B B 9 8 7 6

5

4

3 2 1

CONTENTS PREFACE .............................................................

vii

.

John E Hodge. 1914-19% MILTONS. FEATHER Text

................................................................

1

.

Allene R Jeanes. 1906-1995

NINA M. ROSCHER AND PAULA . SANDFORD Text ................................................................

7

.

Harriet L Frush. 1903-1996 HASSAN S. EL KHADEM Text ................................................................

13

Applications of Tin-Containing Intermediates to Carbohydrate Chemistry T. BRUCEGRINDLEY I. I1. Ill . IV. V. VI . VI1. VIII .

Introduction .................................................... Nomenclature .................................................. Preparation of Tin-Containing Intermediates Physical Methods for the Study of Organotin Derivatives Structures ..................................................... Reaction Types and Conditions Factors That Influence Reaction Regioselectivity ....................... Trends in Regioselectivity ......................................... References

.......................... ................ .....................................

.....................................................

17 18 18 19 25 32 33

44 133

Synthetic Applications of Selenium-ContainingSugars ZBIGNIEW J . WITCZAK AND STANISLAS CZERNECKI 1. Introduction

....................................................

I1. Preparations of Seleno Sugar Derivatives ............................. V

143 145

vi

CONTENTS

............................. ..................................................... References .....................................................

111. Application of Seleno Sugars in Synthesis IV . Conclusion

167 193 195

Anti-Carbohydrate Antibodies with Specificity for Monosaccharide and Oligosaccharide Units of Antigens JOHNH . PAZUR 1. Introduction .................................................... I1. Analytical Methods .............................................. 111. Preparation of Antigens Containing Carbohydrate Residues .............. IV . Immunization Procedure .......................................... V . Preparation and Properties of Anti-carbohydrate Antibodies .............. VI . Conclusions .................................................... References .....................................................

201 203 209 212 213 254 258

Complexes of Starch with Inorganic Guests PIOTRTOMASIK AND CHRISTOPHER H . SCHILLING

I . Introduction .................................................... I1. The Starch-Iodine Complex .......................................

......................................... References .....................................................

111. Starch-Water Complexes IV . Starch Complexes with Other Nonmetallic Guests ......................

263 264 298 312 328

Complexes of Starch with Organic Guests ROTR TOMASIK AND CHRISTOPHER H . SCHILLING V . Introduction Preparation Methods Complexes with Aromas and Flavoring Agents ........................ Complexes with Dyes Complexes with Lipids Starch Complexes with Mono- and Oligosaccharides Starch Complexes with Macromolecules References

.................................................... ............................................. ............................................ ........................................... .................... .............................. .....................................................

346 350 352 376 385 400 405 414

AUTHOR INDEX....................................................... SUBJECT INDEX ........................................................

427 461

VI . VII . VIII . IX . X. XI .

Synthetic work in the carbohydrate field has greatly benefited from new developments in protecting-group strategy and from the introduction of reagents based on heavier elements in the periodic table. Sugars are ideal models for the evaluation of reagents that can specifically bridge two or more oxygen sites. Developments during the past two decades have demonstrated the great value of organotin compounds, especially trialkylstannyl ethers and dialkylstannylene acetals, for effecting useful, high-yielding transformations with high regioselectivity. This volume of Advances features a comprehensive survey, by Grindley (Halifax, Nova Scotia), on the application of tin-containing intermediates to carbohydrate chemistry. In a comparable vein, the element selenium has found important applications in effecting organic transformations. The chapter by Witczak (Storrs, Connecticut) and Czernecki (Paris) on the synthetic applications of selenium-containing sugars surveys key aspects of this still rapidly evolving area. Much of the older work largely parallels the chemistry of the sulfur analogues, but newer developments show novel and versatile potential, particularly in the use of arylselenium reagents for stereochemically controlled addition to glycals and in transformations at the anomeric center. Molecular recognition between carbohydrates and proteins has become a vast area of broad significance in biochemistry and molecular biology. Anti-carbohydrate antibodies have importance in both medicine and technology. The preparation of protein antibodies having specificity for carbohydrate antigens requires application of a range of specialized techniques in molecular separation, the conjugation of carbohydrate ligands to suitable carriers for immunizing animals, and the isolation of pure antibodies from hyperimmune sera. In this volume Pazur (University Park, Pennsylvania), a seasoned Advances author, contributes an article on anti-carbohydrate antibodies with specificity for monosaccharide and oligosaccharide units of antigens. He provides a practical focus on experimental methodology in preparing antibodies having specificity for various sugars and polysaccharides, with many examples developed in his own laboratory. It has been almost two centuries since the first reports on the interaction between iodine and starch to produce a blue color, and more than fifty years since the discovery of the complexation between aliphatic alcohols and starch that revealed this polysaccharide to have a linear and a branched component. A large and diffuse body of published work exists on the interaction of starch and its components with other molecules and with ionic substances. Two closely related chapters in this volume, by Tomasik (Cracow, Poland) and Schilling (Ames, Iowa), provide comprehensive accounts of the extensive literature on complexes of starch with inorganic and with organic guests. vii

viii

PREFACE

Researchers working in industrial or government laboratories often have to rely on their individual experimental efforts in the laboratory and have frequently received less recognition for their accomplishments than have leading scientists in academia, whose work is usually based on extensive experimental work by teams of research students. The three individuals whose lives and scientific contributions are recalled in this volume all made notable discoveries in the carbohydrate field while working in government laboratories and conducting their own experimental work. John E. Hodge, whose career is reviewed by Feather (Columbia, Missouri), laid the major foundations of the chemical basis of the nonenzymatic browning (Maillard) reaction. In the same Peoria laboratory of the United States Department of Agriculture, Allene Jeanes, whose biography is presented by Roscher (Washington, DC) and Sandford (Santa Monica, California), conducted pioneering work on microbial polysaccharides that laid the basis for the commercial development of dextran and xanthan. The memoir contributed by El Khadem (Washington, DC) details the career of Harriet L. Frush, whose teamwork with her mentor, Horace S. Isbell, at the US. National Bureau of Standards and later at The American University in Washington, DC, spanned over sixty years and included seminal contributions in concepts of reaction mechanisms and on the synthesis of labeled sugars. With this volume we welcome David R. Bundle to the Board of Advisors and look forward to valuable input from the prestigious carbohydrate laboratory in Edmonton, Alberta. With regret we record the death, on April 16, 1997, of Elizabeth Percival, a noted authority on marine algal polysaccharides, and on October 14, 1997, of Iqbal R. Siddiqui, who authored the article “Sugars of Honey” in Volume 25 of this series. Washington, DC February 1998

DEREKHORTON

This Page Intentionally Left Blank

ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY. VOL. 53

JOHN E. HODGE 1914-1 996 John Edward Hodge, a distinguished carbohydrate chemist and prominent member of the African-American community, died of cancer on January 3, 1996. John was internationally known, primarily for his work in the area of nonenzymatic browning (the Maillard reaction), which was carried out during his years of service at the United States Department of Agriculture’s Northern Regional Research Laboratories in Peoria, Illinois, where he served on the staff for more than 40 years. John was born in 1914 in Kansas City, Kansas, and spent his early years in that area, before moving to Peoria in 1941. He and his younger sister Dorothy grew up in an atmosphere of learning in the home of their parents, John Alfred and Annabelle Hodge. John Alfred Hodge came to Kansas City from Indiana University in 1910 to teach science at Sumner High School, armed with a newly awarded Master of Science degree in physics. He taught science at Sumner from 1910 until 1916, and then was promoted to the position of principal, remaining in that position for the next 35 years. This was in the days of racial segregation, both in Kansas and the neighboring state of Missouri. Sumner High School, with John Alfred Hodge at the helm, developed a reputation as a serious school with high expectations, accepting only the very best students from the AfricanAmerican community. He was a powerful influence on his own children, and, academically, expected much from both John and his sister. Neither child would be a disappointment in that regard. During childhood, serious reading and science were topics of interest at home. Among some of young John’s interests were the building of model airplanes from balsa wood, and the construction of early radios with his father. John was also interested, as many scientists are, in solving puzzles and playing games of chance. He was well known by contemporaries as an efficient solver of crossword puzzles, and was an accomplished card and checker player, as well as a billiards player. In addition, John was an accomplished musician who played the piano and trumpet, which led to his lifelong interest, an appreciation and love of jazz music. John attended Sumner High School and then enrolled as an undergraduate student at the University of Kansas in nearby Lawrence, Kansas. H e Wfi5-231819R $25.00

1

Copyright 0 1998 by Academic Press. All rights of reproduction in any form reserved.

2

MILTON S. FEATHER

graduated with a degree in mathematics in 1936, having been elected to the prestigious Phi Beta Kappa academic honorary society, as well as the Pi Mu Epsilon honorary mathematics society. During the period from 1936 to 1940, he was employed as a teacher at Western University in Quindaro, Kansas, and as a chemist in the Kansas Department of Inspections, while pursuing advanced studies at the University of Kansas. In 1939, John married Beulah Payne, a fellow chemistry student from St. Louis, who was also enrolled at the University of Kansas. Beulah died tragically in 1942, leaving John with a son, John Laurent Hodge. In 1940, he was awarded an M.S. degree from the University of Kansas in the field of organic chemistry. In 1948 he remarried, to Justina Louise Williams, of Kewanee, Illinois. In the 1930s and 1940s in the USA, it was not an easy task even for a well-educated and intelligent black professional to find a way in life, but John was persistent, always having faith in his abilities and intellect. His opportunity came with the entry of the USA into World War 11, which stimulated considerable development of the national scientific infrastructure, and, with this development, jobs for scientists. The United States Department of Agriculture (USDA) opened four large laboratories in the United States, and John was successful in competing for a position in one of these, the USDA Northern Regional Research Laboratory, in Peoria, Illinois. This laboratory, when it initially opened, had the rather broad mandate to conduct research on agricultural crops that grew in the U.S. heartland, and to develop new products from these crops. John immediately threw himself into research on corn starch and related carbohydrates, and became a self-taught carbohydrate chemist. His initial studies were in the area of the production of D-glucose from corn starch and related technologies. This led to an interest in the interactions between glucose and amino groups, a degradative reaction that poses considerable problems (including loss of sugar) in the production of glucose based on the corn wet-millingprocess. These reactions (the Maillard reaction) became a major research interest from John for the remainder of his life. John was particularly interested in pyrolysis reactions and their role in the production of food flavors and aromas. With his typical thoroughness, he initiated a program that involved the synthesis of Amadori compounds (l-amino-ldeoxyfructose derivatives), since it was commonly considered that these are the first intermediates formed during the Maillard reaction and serve as precursors of many of the degradation products that are known to be formed. He was able to prepare a number of these compounds, in crystalline from, by reacting piperidine with glucose, as well as with maltose and lactose, and he used these products in many of his pyrolysis experiments. Out of this research came a number of new findings. He was able to demonstrate that isomaltol, a bakery aroma constituent, is directly produced

JOHN E. HODGE

3

from an Amadori compound and that it is, in fact, a furan derivative (2acetyl-3-hydroxyfuran).Isomaltol was first isolated in Germany in the late 1800s from the effluent from a bakery flue, and had been assigned a pyrone structure. John and his colleagues also were able to show that “piperidino lactulose,” an Amadori compound formed by reacting lactose with piperidine, undergoes pyrolysis to give galactosylisomaltol, a fact that provided confirming data on the mechanism of isomaltol formation from sugars via Amadori compounds. These Amadori compounds were also instrumental in his work on the mechanism for formation of maltol(3-hydroxy-2-methyl4H-pyran-4-one), a sugar-derived pyrone that is also a flavor and aroma constituent, often found in baked cereal products. John also investigated the reductones that are produced during the Maillard reaction, in collaboration with Professor Friedrich Weygand of the University of Munich. Together, these two scientists carried out numerous investigations on the mechanism of their formation. One of Hodge’s reviews, which appeared in the Brewing Chemists Society Proceedings in the 195Os,became a “citation classic,” and the scheme proposed in it for reductone and color formation during the Maillard reaction remains a widely cited publication today, more than 40 years after its publication. During his tenure at the Northern Regional Research Laboratory, John received numerous awards and recognitions. He served as the chairman of the American Chemical Society’s Division of Carbohydrate Chemistry, and he received a number of USDA awards, including a Superior Service Award in 1953.John served as an adjunct professor of chemistry at Bradley University in Peoria and taught a course in carbohydrate chemistry at that institution for a number of years. In 1972, he was designated a Visiting Professor at the University of Campinas in Silo Paulo, Brazil, where he spent a semester teaching carbohydrate chemistry and interacting with graduate students at that institution. Later, as one of the pioneers in his field of research, John was honored at the NIH Conference on the Maillard Reaction in Aging, Diabetes, and Nutrition, held in Bethesda, Maryland, in 1988. John was an engaging man of quiet temperament but firm determination. He was active in the African-American community and served as a role model for many aspiring African-American scientists. He had the respect of both black and white Americans. He was elected to Who’s Who among Black Americans in 1980, and served on a number of local committees in Peoria, including the Board of Directors of the Carver Community Center, the Citizens’ Committee for Peoria Public Schools, and the Central Illinois Agency on Aging. He was outspoken against the abolition of competency tests and the lowering of academic standards. John is survived by his wife, Justina Hodge, of Peoria; two sons, John Laurent of Brookline, Massachusetts, and Jay Mitchell of Peoria; two

4

MILTON S. FEATHER

daughters, Judith Ann Dunmore of Milton, Massachusetts, and Justina Louise Mitchell of Washington, D.C.; and one sister, Dorothy Johnson of Kansas City, Missouri. This writer is deeply indebted to and acknowledges the following persons for their help in the preparation of this article: Mrs. Dorothy Johnson (sister) of Kansas City, Missouri, for a number of helpful discussions relative to John’s childhood and early life; Mrs. Justina Hodge (widow), of Peoria, Illinois, for access to archival materials; and Dr. William Doane (colleague) of Peoria, Illinois, for detailed information on John’s professional life while he was on the staff at the Northern Regional Research Laboratories in Peoria. MILTON S. FEATHER

This Page Intentionally Left Blank

ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL. 53

ALLENE R. JEANES 1906-1995 On December 11,1995, Allene Rosalind Jeanes passed away in Urbana, Illinois. No one who had met her will easily forget her. Dr. Jeanes, as she was usually called by her colleagues, will be remembered as an extremely serious and dedicated person who devoted most of her professional career to the characterization of dextran and xanthan, two microbial polysaccharides of exceptional practical importance. She was born in Waco, Texas, on July 19, 1906, to Largus Elonzo and Viola Herring Jeanes. She and her older brother, Perry, grew up in Waco. Their father was a switchman and later yardmaster for the Cotton Belt Route of the St. Louis Southwestern Railroad. Allene graduated “with honors” from Wac0 High School in 1924. In 1928, she graduated summa cum laude from Baylor University with the A.B. degree in chemistry. Next, she went to the University of California, Berkeley, where in 1929 she obtained the M.A. degree in organic chemistry. After a brief time as a high-school mathematics teacher in Laredo, Texas, she taught chemistry and biology from 1930 to 1935 at Athens College, Alabama, and was head of the Science Department. In 1936, Allene Jeanes’ yearning for research led her to graduate studies at the University of Illinois (Champaign-Urbana), where she studied in the laboratory of the famous organic chemist Roger Adams, majoring in chemistry with a minor in biochemistry. She was an instructor in the Chemistry Department (1936-1937) and later Chemical Foundation Fellow (19371938). In 1938 she was awarded the Ph.D. degree in organic chemistry. Fortunately for carbohydrate chemistry, and with Prof. Adams’ insistence, Dr. Jeanes decided to accept a position at the National Institutes of Health (NIH) in Washington D.C., in the laboratory of the celebrated carbohydrate pioneer Claude S. Hudson. Her support came from one of the first Fellowships of the Corn Industries Research Foundation. With Hudson she developed methods using periodate oxidation to determine the structure of starches, marking the start of her long fascination with carbohydrate polymers. Dr. Jeanes then continued her studies of carbohydrates with Dr. Horace Isbell at the National Bureau of Standards (now the National Institute of Standards and Technology). WS-2318198 $25.W

I

Copyright 0 1998 by Academic Press. All rights of reproduction in any form reserved.

8

NINA M. ROSCHER AND PAUL A. SANDFORD

In early 1941, Dr. Jeanes moved back to Illinois, this time to Peoria, just three months after the opening of the US. Department of Agriculture’s Northern Regional Research Laboratory (NRRL, later NRRC, and now the National Center for Agricultural Utilization). She continued to work there even after her retirement in 1976. Her more than 35 years of research at NRRL resulted in two major scientific and industrial developments, dextran and xanthan, and these are described in more than 60 publications, 24 presentations, and 10 patents. Her early endeavors to characterize the branch points in starch, and pursuit of the then-elusive a-(1 + 6) linkage in starch, drew Dr. Jeanes to dextrans, since these polysaccharides contain a-(1 + 6) linkages as their main structural feature. Dextrans are a family of D-glucans produced microbially from sucrose; they contain from 50 to 100% a-(1 + 6) linkages, depending on the microbial strain used. Dr. Jeanes became an authority on dextran sources, structures, and industrial applications. She published comprehensive bibliographies on dextran, the first in 1950 and another in 1978. These were a labor of love, produced with much effort before the days of automated data retrieval. A dextran-producing strain (NRRL B-512) of Leuconostoc mesenteroides was isolated from unpasteurized root beer in Peoria and brought to NRRL for characterization. This strain later became the source of a substrain, B512(F), that would be used widely to produce dextran for such pharmaceutical applications as “clinical dextran,” a blood-plasma extender. Crosslinked B-512 dextrans constitute the familiar Sephadex packing materials used for size-exclusion column-chromatographic separations, and dextrans are commonly used as molecular-weight standards in liquid chromatography. In 1950, during the time of the Korean conflict, Dr. Jeanes’ initial research with dextran formed the basis of a multidisciplinary crash program with 80 scientists that was started at NRRL to develop a blood-plasma substitute based on dextran. Dr. Jeanes and her immediate research group played an important role in the isolation and characterization of dextrans from more than 100 bacterial strains. Dr. Jeanes was a member of the Subcommittee on Plasma and Plasma Substitutes of the Medical Division, National Academy of Sciences National Research Council, from 1962 until 1968. In 1953, USDA’s highest award, the Distinguished Service Award, was given to Dr. Jeanes, and NRRL’s Dextran Team received the award in 1956. The American Chemical Society awarded her the Garvan Medal in 1956. Dr. Jeanes received the 1962 U.S. Civil Service Commission’s Federal Women’s Award, and in 1968, her alma mater, Baylor University, conferred on her the Outstanding Alumna Award. Based on the success with dextran, Dr. Jeanes and her colleagues started exploring other microbes as agents for producing useful polysaccharides.

ALLENE R. JEANES

9

At NRRL the goals were first to find new outlets for cereal starches by using bacteria and fungi capable of converting them into new types of extracellular polysaccharides (gums), and second to develop domestic sources of thickening, suspending, and stabilizing agents to replace imported polysaccharide gums. At the start of this project about 30 microbial strains were identified as potential candidates. After small quantities of each were isolated for characterization, the 15 most interesting candidates were extensively characterized, both in terms of structure and rheological properties. The bacterial polysaccharide xanthan (Dr. Jeanes disliked the term “xanthan gum”), the second candidate on this screening list, produced by the plant pathogen Xunrhomonus campesrris NRRL B-1459 growing on a Dglucose medium, became the second blockbuster product to be commercialized based on the research of Dr. Jeanes’ team. Dr. Jeanes’ biopolymer team literally taught the fermentation giants of the world how to make xanthan, thus starting a new industry-microbial polysaccharides. Xanthan became the model of how to produce other microbial polysaccharides. Dr. Jeanes’ work demonstrated that the properties of each polysaccharide derive from its monosaccharide composition and linkage arrangements. Xanthan, used as a thickening agent in a myriad of food and nonfood applications, is currently manufactured in vast quantities by several companies worldwide. In 1968, the Biopolymer Research Team at NRRL was given the USDA Superior Service Award, based on their work that resulted in the commercialization of xanthan. Many people will remember Allene Jeanes as a rather thin, somewhat frail, gray- to white-haired woman who was soft-spoken but very intense and deliberate in her mannerisms. She never married. Woe to the person who thought she, being a woman, should be granted a lesser status as a researcher. She overcame with determination the many obstacles placed in the path of women researchers of her day. Her attitude was not one of boasting, but rather of sound reasoning and thorough preparation. She was extremely patient both with her colleagues and with the numerous visitors who came to her laboratory seeking detailed information about her polysaccharide research. She would spend as much time as desired with anyone willing to learn about her favorite polysaccharides. Some of her colleagues thought she spent too much time planning experiments and then finally writing and rewriting manuscripts. However, any co-experimenter or coauthor soon learned to pay attention to details. As for members of her team, she would fight for their rights and would try to advance their professional careers as much as possible, but her standards were high. Dr. Jeanes’ patience and dedication to details allowed her to make significant contributions to carbohydrate chemistry and biochemistry. She was a true pioneer in the use of microbial polysaccharides for industrial applications. In 1978

10

NINA M. ROSCHER AND PAUL A. SANDFORD

she was recognized by research colleagues and friends worldwide who dedicated papers to her in a special issue of the journal Carbohydrate Research. Dr. Jeanes’ last published paper, “Immunological and Related Interactions with Dextrans Reviewed in Terms of Improved Structural Information,” was published in 1986 (Molecular Immunology, 23, 999-1028), 10 years after her “official retirement” and only 9 years before her death. It demonstrates the dedication this lovely woman had for her first lovedextran.

NINAM. ROSCHER PAULA. SANDFORD

This Page Intentionally Left Blank

ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL. 53

HARRIET L. FRUSH* 1903- 1996

Harriet Louise Frush was one of the pioneering women scientists who entered the field of carbohydrate chemistry in the 1920s and with perseverance and hard work was able to succeed. At that time there were few women chemists in U.S. Government agencies, and hardly any on the faculty of most universities. Her career was not easy; to be accepted by her peers she had to prove herself in research, yet when she had done so, her position was terminated. Although later reinstated, she was overshadowed by her co-workers and never quite received the recognition she deserved. This memoir draws attention to her many accomplishments in the carbohydrate field. Harriet L. Frush, the daughter of Frank and Rose (Miller) Frush, was born on July 3, 1903, in Knoxville, Iowa, a little town southeast of Des Moines. When she was 3 years old, her parents moved to nearby Pella, Iowa, where she grew up and went to school. An excellent student, she was generally at the top of her class. In 1924 Harriet received a Bachelor of Science degree from Central College in Pella, Iowa, and enrolled in graduate school at the University of Iowa. There she received a Master of Science degree in chemistry in 1928, and was appointed in the following year as a chemist in the National Bureau of Standards in Washington, D.C. (presently the National Institute of Standards and Technology in Gaithersburg, Maryland). She was assigned to work in the Polarimetry Section under Dr. Horace S. Isbell, a rising star in the field of carbohydrate chemistry. She enjoyed working with him, and as time passed, the two developed a great admiration and profound respect for each other. The scientific collaboration that started between them at that time lasted for more than 60 years, making it one of the longest and most fruitful collaborations in the field of chemistry (probably the longest, if one discounts the work of such husband-and-wife teams as the Fiesers).

*

The information presented here was gathered during lengthy discussions with Dr. Harriet Frush and Dr. Horace Isbell. as well as from correspondence with Dr. Robert Schaffer, her superior at the National Bureau of Standards, and her niece Roselyn Lomax. The contributions of the last two are gratefully acknowledged.

W65-2318/98$25.00

13

Copyright B 1998 by Academic Press. All rights of reproduction in any form reserved.

14

HASSAN S. EL KHADEM

Harriet Frush’s first papers from the National Bureau of Standards dealt with the electrolytic oxidation of sugars to aldonic acids. The process she developed was so successful that it was adopted by industry for the production of calcium gluconate (extensively used pharmaceutically as a calcium supplement). The policy of the Bureau prevented employees from patenting their discoveries, but it was estimated that royalties from such a patent would have been worth millions in today’s dollars. It was therefore surprising that, when budget considerations necessitated a reduction in the staff of the National Bureau of Standards, Harriet was terminated in 1933. Fortunately the layoff was temporary, and a few months later she was rehired and assigned to the Cement Section, where she worked for some time as an analytical chemist. She enrolled in the Ph.D. program at the University of Maryland and selected as her thesis advisor Dr. Horace Isbell. A short time later, she succeeded in moving back to the Polarimetry Section, where she resumed work on her favorite subject, carbohydrate chemistry. She published several important papers on the reactions of glycosyl halides and received the Ph.D. degree in 1941. In her thesis she describes how the stereochemistry of glycosyl halides dictates the reactions that they undergo and the nature and configuration of the products formed. She found that orthoesters are produced when a leaving group is trans-oriented to an adjacent acetate group. Consequently, nucleophilic attack on a glycosyl halide can occur either on the carbonyl group of a properly oriented 2acetate to give a cyclic orthoester (which may undergo a second attack to afford a product having the same configuration as the starting material), or on the anomeric carbon to yield a product having an inverted configuration. The phenomenon was named the “neighboring-group effect.” Between 1941 and 1949, Harriet Frush worked on uronic acids and glyculosonic acids obtained from pectins, algins, and citrus products, and published her results in a number of pioneering papers. During the next 18 years she devoted her efforts to a project that generated her most important contribution to carbohydrate chemistry-namely, the synthesis of I4C- and 3H-labeled carbohydrates. The work was initiated in the 1950s by a grant from the then Atomic Energy Commission. Although most of the chemists in the Organic Chemistry Section in the National Bureau of Standards worked at one time or another on this major project, most of the work on 14C-labeledcarbohydrates was carried out by Horace Isbell, Harriet Frush, and Robert Schaffer, and the work on 3H compounds by Horace Isbell, Harriet Frush, and Lorna Sniegoski. First the carbon-labeled compounds were prepared by the action of 14C-labeledHCN on pentoses and tetroses, and later the tritium-labeled compounds were prepared by reduction of unlabeled aldonolactones with labeled borohydride or with sodium amalgam in tritiated water. From the resulting labeled products, saccharides

HARRIET L. FRUSH

15

could be produced having the radioactive isotopes of carbon and hydrogen in all the desired positions in their molecules. The samples prepared by the National Bureau of Standards were either used on campus in various research projects, or supplied to scientific institutions in the United States and elsewhere, where mechanistic studies helped solve important chemical and biological problems. Many of the methods Harriet developed were later adopted by industry for the manufacture of labeled sugars or modified in order to prepare the l3C-1abeled sugars needed for NMR work. Harriet Frush worked in the National Bureau of Standards from 1929 until 1968, during which period she published 60 papers, most of which appeared in the Journal of Research of the National Bureau of Standards. In 1968, Horace Isbell reached the mandatory retirement age in the Bureau of Standards, and it seemed that the much-admired work of the Isbell-Frush research team was about to come to an end. However, Isbell was not ready to stop his research work and decided to accept a position of Research Professor at American University in Washington, D.C. Harriet Frush, in turn, joined the Department of Chemistry at the American University, taking early retirement from the Bureau and being appointed Research Scientist at American University. This preserved the Isbell-Frush team and enabled the collaboration between the two chemists to continue for another 24 years, until 1992, when Isbell died. At American University, Harriet Frush and Horace Isbell worked on the mechanism of oxidation of carbohydrates by peroxides. They discovered that, in aqueous alkaline hydrogen peroxide, aldoses are quantitatively degraded to formic acid, so that hexoses produce six moles of this acid and pentoses produce five moles. A detailed study of the mechanism of the reaction revealed that degradation takes place by several pathways, the most rapid one involving the formation of peroxy radicals and hydroxy radicals. Thus, when a hydroperoxide-aldose adduct reacts with hydrogen peroxide, a peroxy radical is formed, which decomposes to a hydroxy radical, formic acid, and the next lower aldose. It was also found that, under basic conditions, hydroxy radicals oxidize alditols and aldonic acids to carbonyl compounds in much the same way they do with Fe2+in the Fenton reaction. During the years she spent at American University, Dr. Frush was able to publish 10 papers without help from any research assistant or laboratory technician. This brought her total to more than 70 papers. Harriet Frush was a very nice, devoted, and genteel person, reserved and unassuming, kind and always ready to help. She loved music and played the piano, organ, and flute quite well, often entertaining her friends with short pieces of baroque music. Her great hobby was travel, and she spent many of her vacations touring the United States and the world. Harriet was most of all a very modest person and hated being fussed about. One

16

HASSAN S. EL KHADEM

day, Dr. Horace Isbell wanted to nominate her for an important award and asked for her consent to put forward her name, but she refused, stating that she had done nothing to deserve such recognition. She was also a giving person who, in spite of her failing health, continued to deliver “Meals on Wheels” to the elderly until she could no longer drive. Harriet Frush never married; her closest relatives were the three children of her younger sister, Marion Vander Wert. The last major work of Harriet Frush at the American University was a collaborative effort with the present writer, the editing of the Complete Works ofHorace S. Isbell, a three-volume series published by the Carbohydrate Division of the American Chemical Society in 1988. Her health subsequently deteriorated, and she rarely came to the University, staying at home to take care of her ailing friend, Mary Jane Young. Later, the two went to a retirement home, in Knoxville, Illinois, to be near Harriet’s niece Roselyn Lomax. Harriet Frush died on November 16,1996, during surgery for a broken hip. HASSANS. EL KHADEM

ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY. VOL. 53

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES TO CARBOHYDRATE CHEMISTRY

BYT. BRUCE GRINDLEY Department of Chemistry. Dalhousie University. Halifax. Nova Scotia. Canada B3H 4.73 I . Introduction ...................................................... 17 I1. Nomenclature 18 111. Preparation of Tin-Containing Intermediates ............................ 18 IV . Physical Methods for the Study of Organotin Derivatives ................... 19 19 1. Tin-119 NMR Spectroscopy ........................................ 2. Carbon-I3 and Proton NMR Spectroscopy., 25 V . Structures ........................................................ 25 1. Tributyltin Ethers 25 2. Dialkyltin Dialkoxides and Dialkylstannylene Acetals ................... 26 VI . Reaction Types and Conditions ....................................... 32 VII . Factors That Influence Reaction Regioselectivity ......................... 33 1. Tributylstannyl Ethers ............................................ 33 2. Dialkylstannylene Acetals ......................................... 36 VIII . Trends in Regioselectivity ........................................... 44 44 1. Symmetrical Diols and Polyols ..................................... 2 . trans-Diols and Polyols Containing Only trans-Diols .................... 44 3. cis-Diols and Polyols Containing cis-Diols ............................ 71 4 . Diols Adjacent to Deoxy Centers or Double Bonds ..................... 103 5. Terminal 1,2- and 1,3.Diols ........................................ 110 6. Glycoside Formation ............................................. 124 7. Miscellaneous .................................................. 129 133 References .......................................................

..................................................... .......................... ...............................................

1. INTRODUCTION Since the discovery’.’ of their utility in 1974. trialkylstannyl ethers and dialkylstannylene acetals have become widely used intermediates in the synthesis of carbohydrate derivatives . Although the use of these intermediates has been reviewed several times:-’ innovative developments continue to be described; marked advances have been made both in expanding the utility of these compounds and in understanding of the mechanisms of the reactions . The major reason that these intermediates have become widely employed is that they provide reliable. high-yielding methods for obtaining monosubsti0065-23111198 $25 IN1

17

Copyright 6 1998 by Academic Press . All rights of reproduction in any form reserved .

18

T. BRUCE GRINDLEY

tuted derivatives of diols or polyols, often with high regioselectivity. In addition, the reactions occur under much milder conditions or at rates that are much higher than those of the parent alcohols. As a result, these reactions have become part of the arsenal of techniques commonly used by organic chemists, and numerous publications in which they are used appear each year. This report is a comprehensive summary of this area. It is intended that all results using these intermediates should be included; however, these methods have become so common that routine results are often not highlighted, and some applications may have been inadvertently omitted. 11. NOMENCLATURE Dialkyltin dialkoxides, in which the dialkoxides are connected to form a ring are called dialkylstannylene acetals, or more properly, 2,2-dialkyl1,3,2-dioxastannolanes, if the ring is five-membered; 2,2-dialkyl-1,3,2dioxastannanes, if the ring is six-membered; or 2,2-dialkyl-1,3,2dioxestannepanes, if the ring is seven-membered. Trialkyltin alkoxides are normally termed trialkyltin ethers or trialkylstannyl ethers. The sugar derivatives are named by standard acetal (2-Carb-28) or ether (2-Carb-24.1) nomenclature.' 111. PREPARATION OF TIN-CONTAINING INTERMEDIATES The most widely employed tin-containing intermediates are dibutylstannylene acetals and tributylstannyl ethers. Dibutylstannylene acetals are usually prepared by reaction of diols with dibutyltin oxide in methanol with heating, or in benzene or toluene with azeotropic removal of water using a Dean-Stark apparatus (Fig. 1).The latter conditions probably result in complete conversion in 1-2 h at reflux, although they are normally left 4-24 h. Incorporation of a Soxhlet apparatus containing molecular sieves toward the end of the reaction ensures complete removal of water. Reaction in methanol, where dibutyldimethoxytin is an intermediate for the preparation, is more rapid, often being complete in 1 h; however, one group observed that yields were lower and that starting material remained after reaction workup if the dibutylstannylene acetal was formed by this method.' The technique used for preparation may also have been a factor in the

-(

0

+ Bu$nO

+

$0

FIG.1 .-Formation of a dibutylstannylene acetal.

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES 2ROH + (Bu,Sn),O

*[ROH

+ Bu,SnOR + Bu,SnOH]-

FIG.2.-Formation

19

ZROSnBu, + H,O

of a tributyltin ether.

yields reported by KovhE and Edgar," who formed the stannylene acetal in toluene, which were higher than those reported for identical reactions by earlier workers, who formed it in methanol." Most reports in which dibutylstannylene acetals are formed in methanol give excellent yields; it is probably sufficient to use carefully dried methanol and to be very careful to remove the methanol completely at the end of formation of the dibutylstannylene acetal, to ensure complete conversion. The use of performed dibutyltin dimethoxide is advantage~us'~-'~; reactions of diols are complete in 5-15 min in benzene at reflux. This technique avoids the problems with working in methanol just mentioned, and gives better yields. The preparation of stannylene acetals is also accelerated by microwave irradiati~n,'~ and selective reactions can be performed, albeit in low yields, on some diols and polyols by microwave irradiation in the presence of a catalytic amount of dibutyltin oxide.16.17 Tributylstannyl ethers are prepared in the same manner by reaction of alcohols with hexabutyldistannoxane (more commonly known as bistributyltin oxide). Holzapfel et al. noted that the reaction in benzene requires only 0.5 molar equivalents of bistributyltin oxide to go to completion but takes 16 h at reflux (Fig. 2). This is probably because the tin-containing by-product of the first half of the reaction, tributyltin hydroxide, reacts much more slowly than the initial reagent.18 Dibutyltin oxide, dibutyltin dimethoxide, and hexabutyldistannoxane are commercially available. Di-t-butyltin dichloride is commercially available, but reactions of di-t-butylstannylene acetals are often very slow. In certain cases, there are advantages in using bulkier tin oxides or tin oxides that are sterically restricted, such as cyclic tin oxide^.^^.^^ Non-commercial dialkyltin oxides may be prepared conveniently by the reaction of dialkyldiphenyltin with chloroacetic acid followed by sodium hydroxide.21 This procedure works well for the preparation of stannacycloalkanes as well as bulky dialkyltin oxides. IV. PHYSICAL METHODS FOR THE STUDY OF ORGANOTIN DERIVATIVES

1. Tin-119 NMR Spectroscopy The most convenient technique available to study organotin compounds The Il9Sn nucleus has a spin of in solution is "'Sn-NMR %and a natural abundance of 8.7%;it is about 25.5 times more sensitive than

T. BRUCE GRINDLEY

20

13C,taking into account the isotopic abundances. The '"Sn isotope, also a spin ?hnucleus, with a natural abundance of 7.7%is slightly less sensitive and has been little used. It is about 19.7 times more sensitive than I3C.Since both of these nuclei have negative magnetogyric rations, nuclear Overhauser enhancements are negative. Thus, spectra are normally recorded with decoupling on only during acquisition. It should be noted that NOESonly occur if the tin atoms relax through dipole-dipole interactions with protons. A limited number of relaxation studies of organotin compounds have been performed. Tin atoms in simple compounds in which the tin atoms are tetracoordinate relax by the spin-rotation mechanism, but dipole-dipole relaxation becomes more important as the molecules get larger and the temperature becomes l o ~ e r ? ~Since - ~ l they are in still larger molecules, the tin atoms in tributyltin ethers of carbohydrates relax predominantly by the dipole mechanism, with TI values in the 2- to 7-sec range.32In contrast, tin atoms in the pentacoordinate and hexacoordinate environments present in stannylene acetals relax predominantly by chemical-shift anisotropy, with relaxation times in the 0.02- to 0.2-sec range at 8.5 T (360 MHz ~pectrometer).~~ This allows much shorter pulse intervals, and the effectiveness of this mechanism increases with the square of the applied magnetic field strength. These relaxation times are short enough that they cause the line widths to be broad; if TI is 20 msec, the contribution to the line width from relaxation is 16 Hz, offsetting the gain in intensity arising from short pulse intervals. Chemical shifts for tin atoms in typical carbohydrate-derived organotin compounds are listed in Tables I and 11. In general, the signals of Il9Sn

TABLE I Typical ll'Sn NMR Chemical Shifts of Tributvltin Ethersa Compound

Solvent

Chemical Shift

Reference

Tributyltin propoxide Tributyltin isopropoxide 1

Neat Neat Toluene Toluene Toluene Toluene Benzene Benzene Benzene Benzene Benzene Benzene

87 76 99.0 86.4 92.8, 98.6 77.5 (C-2), 91.2 (C-3) 78.5, 90.4 102.5 90.0 73.9 (C-3), 101.6 (C-4) 113.5 119.4

34 34 35 35 35 35 36 36 36 36 36 36

2 3 4 5 6 7 8 9 a

In ppm from tetramethyltin.

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

21

nuclei in tributyltin ethers appear between 75 and 105 ppm if no hydroxyl groups are on adjacent carbons, but are deshielded by up to 20 ppm more if hydroxyl groups are cis and vicinal to the tributyltin ether (Table I). The presence of a trans-hydroxyl group causes a lesser deshielding of about 10 ppm. Presumably, these effects are caused by equilibria in which there are small contributions from species in which hydroxyl oxygen atoms have added to tin atoms to form five-membered rings.

Me0

. 1

OMe

OSnBu,

OMe

2

3

Bu,SnO OMe

4

5

Bu,SnO

HO

OMe

6

OBn

7

Tin-carbon coupling constants can be useful in making assigments for tributyltin ethers. Values for 2JC,Sn lie between 22 and 32 Hz if the carbons are ~econdary,~'. 36 but are larger for primary carbons (46 Hz for one example3'). The 3JC,sn values are of similar magnitude, ranging35,36from 10

T. BRUCE GRINDLEY

22

SnBu,

FIG.3.-Three-bond tin-carbon coupling constants?6

to 29 Hz. These values probably follow a Karplus-type relationship since, in several examples, the magnitudes of coupling constants from tin atoms on axial oxygen atoms have values at the low end of the range to one carbon (presumably gauche) but at the high end of the range to the second carbon (presumably anti) (see Fig. 3). Tin atoms in dibutylstannylene acetals resonate between -115 and -150 pprn if they are pentacoordinate in five-membered rings. If they are hexacoordinate in five-membered rings, the tin nuclei are considerably shielded to between -220 and -330 ppm, with the more deshielded values being observed for polymers and higher oligomers (Table 11). Pentacoordinate tin atoms in six-membered rings are more shielded than those in fivemembered rings, by about 50 or 60 ppm to about -180 ppm (see results for compounds 16 and 23). Those in seven-membered rings appear at intermediate shifts (see 25 and 26).Replacement of butyl groups by t-butyl groups results in the shielding of the tin atom by about 100 ppm (compare data for compounds 10 and 13 and also for compounds 21b and 24), and intermediate changes in branching on the carbon attached to the tin atom bring intermediate shift change^.^' Bu\ Bu\

3"\

/Bu

Bu\ /Bu

8"\

/Bu

O W 0

10

/""\

H?3w w 11

12

t-Bu\

fBu

/""\

13

14

15

Bu,

,Bu

/""\ O U O

16

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

23

ph

k

Ph

ok

0

OBn

\

BuHSn\

No

Bu

Bu Bu

OBn

0

20

OBn

21a R = M e 21b R = B n

Bu

Nsnp+o& BnO

23

22

OR

OBn

OBn

24

H BnO

25

OBn

26

OMe

TABLE I1 Typical lI9Sn NMR Chemical Shifts for Dialkylstannylene Acetals

Solvent

Compound 10

Chloroform

11

Solid state Chloroform/dichlorofluoro-methane3 :1

14

Chloroform Chloroform Solid state Chloroform

15 16

Chloroform Chloroform

12

13

17

18 19

20

2lb

22

23 24 25 26

Solid state Chloroform Toluene Solid state Chloroform

Coordination Status 5 5, 6 5, 6 6 5

5, 6 5 5 5 5 4 4 5 5, 6 6 5 5 5 5

Toluene

5 5 5 5 5, 6 5, 6

Chloroform Chloroform Chloroform Chloroform Chloroform

5 5 5 5 5

Chloroform Solid state Chloroform Chloroform

Oliomer Name Dimer Trimer Tetrarner Polymer Dimer Trimer Dimer Dimer Dimers Dimer Monomer Monomer Dimer Trimer Polymer 3,3-Dimer 3,3-Dimer 3,3-Dimer 2,3-Dimer 2,2-Dimer 2,2-Dimer Dimer Dimer Trimer Trimer Tetramer 6.6-Dimer 6,6-Dimer Dimer Dimer Dimer

Chemical Shift -126.8 -126.8, 283.0 -131.4, -266.0 -231 - 141.5 -142.5, -291.8 -139.8 -225 -222, -224, -225, -226 - 127.9 80 -20.4 -187.8 -195.1, -346.1 -279.5, -281.8 -125.4, -124.9 -131.6 -126.8, -128.6 - 132.6 -132.8, 133.0 -145.1, -143.8 -141 -125.6 - 123.4 -117.4, -122.5, -283.3 -116.8, -124, -287 -124.1, -243.4 -119.6 -180 -217.7 - 150.8 - 160.2

Reference 38 39 38 38 40 39 41 41 42 43, 44 35 39 44 43, 44 39 43 41

37 43 39 43 45

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

25

2. Carbon-13 and Proton NMR Spectroscopy Carbon-13 and proton NMR specta are much less useful than “’Sn NMR spectra in providing information about the structures for these organotin intermediates, but can serve useful roles in mechanistic studies. HoleEek et al. have measured 13C NMR data for a wide range of dibutyltin( IV) corn pound^.^^ Chemical shifts for C-1 to C-4 of butyl groups in simple dibutyltin dialkoxides have values of about 19, 27, 26, and 13 ppm, re~pectively.~~ The chemical shifts of the C-1 carbons are somewhat dependent on the nature of the compound and its state of association. For 2,2-dibutyl-l,3,2-dioxastannane, the chemical shift of the butyl C-1 was about 20 pprn when the attached tin atom was pentacoordinate, but about 27 pprn when it was hexacoordinate?2 Probably a more useful parameter is the lJsn-lly,c coupling constant. The magnitude of this parameter has been shown to increase linearly with the size of the C-Sn-C b0nd-angle.4~9~~ These one-bond coupling constants are large and vary widely (307 to 1175 Hz), but have not been extensively employed for the study of carbohydrate derivatives. For butyl groups attached to pentacoodinate tin atoms, values of about 580 to 620 Hz and and 1,3650 Hz have been observed for simple 1,3-dio~astannolanes~~*~ dioxastannanes,42 respectively, at low temperature. Average roomare larger, 6534’ or temperature values for 2,2-dibutyl-l,3-dioxastannolane 643 Hz5’, indicating that the values for hexacoodinate tim must be still greater, consistent with the expected and observed larger C-Sn-C bond angles for hexacoordinate tin.42,S1*52 Chemical-shift changes for carbon nuclei in the diols on substitution of hydroxyl hydrogen atoms by a tin atom are small (<6 ppm, normally < 4 ppm) and rather ~npredictable.~’.~ It might be expected that the carbon atom attached to the tricoordinate oxygen atom in a dibutylstannylene acetal would be deshielded because of the assumed positive charge on the oxygen atom. In fact, the chemical shifts of these carbon atoms are almost identical to those of the parent dials.# Roelens has made extensive use of the ‘H NMR chemical-shift changes when an organotin intermediate is treated with an acylating agent, to study the intermediates involved in these pro~esses.5~ V. STRUCTURES

1. Tributyltin Ethers In the solid state, trimethyltin methoxideS4and trimethyltin hydro~ide~’+’~ are linear polymers. The tin atoms are pentacoordinate, with distorted trigonal bipyramidal geometries having apical oxygen atoms. In solution

26

T. BRUCE GRINDLEY

in nonpolar solvents, simple and more complex trialkyltin alkoxides exist predominantly as monomers with tetrahedral tetracoordinate tin atoms. This conclusion was determined by molecular-weight measurements and from l19Sn NMR chemical shifts, which are diagnostic for coordination s t a t ~ s . Formation ~ ~ - ~ ~ of tributylstannyl ethers from a polyol using less than a stoichiometric amount of bistributyltin oxide yields a mixture that contains all possible tributylstannyl These tributyltin ethers do not interconvert rapidly on the NMR time scale in benzene up to 100°C, but do interconvert rapidly under normal reaction condition^.^^.^^ The presence of added nucleophiles, such as tetrabutylammonium hal i d e ~ or ~ ' N-methylimidazole (NMI)," markedly accelerates reactions with electrophiles. In the presence of NMI, the l19Sn nuclei are more shielded, consistent with the changes in chemical shift observed when tin nuclei assume higher c ~ o r d i n a t i o n .The ~ ~ shift changes are relatively small on addition of 1equiv of NMI at room temperature (<26 ppm) in comparison to the shifts observed when the temperature is lowered to -80°C ( 4 7 5 ppm), or when 3 equiv are added at room temperature ( 4 9 ~ p m ) . ~ ~ The rate of change in chemical shift with temperature had lessened at the lowest temperatures studied, but it did not appear that limiting values had been reached.36These results indicate that a rapid equilibrium occurs between the uncoordinated tributylstannyl ethers and one or more species in which the tin atoms have coordination higher than 4. The relatively small chemical-shiftchanges observed on addition of 1equiv of NMI at room temperature indicates that the uncoordinated species are much more highly populated than the coordinated species at room temperature and above.

2. Dialkyltin Dialkoxides and Dialkylstannylene Acetals Acyclic dimethyltin or dibutyltin dialkoxides exist as dimers in solution unless the alkoxy groups are large, for example, t-butoxy groups, where they are present as monomer^.^^.^^ Compounds having intermediate-sized groups, such as neat dibutyltin diisopropoxide, are present as mixtures of monomers and dimers that shift to monomers on dilution or h e a t i ~ ~ g . ~ ~ . ~ ' Based on chemical-shift data for dimethyltin dialkoxides and dibutyltin dialkoxides as a function of temperature, Kennedy has suggested that the bond-dissociation energies for the intermonomer Sn-0 bonds are about 35 kJ/mol. This bond dissociation also requires conversion of pentacoordinate tin to tetracoordinate tin. For methyltin trialkoxides, association to form oligomers is also observed. For these compounds, dimer Sn-0 bond dissociation energies are about the same, but Sn-0 bond dissociation energies for tetramers going to dimers, which also requires hexacoordinate tin to become pentacoordinate tin, are much lower, only <10 kJ/mol."

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

FIG.4.-Structures

27

OBu present for dibutyltin dialkoxides.

2,2-Dibutyl-1,3,2-dioxastannolane its (4R,SR)-4,5dimethyl derivative,”’ and 2,2-dibutyl-1,3,2-dioxastannane(16)42 exist as infinite polymers in the solid state with octahedral hexacoordinate tin atoms. Compounds having larger substituents are less aggregated in the solid; 2,2-di-t-butyl-l,3,2-dioxastannolane(13);’ methyl 4,6-O-benzylidene2,3-O-dibutylstannylene-a-~-glucopyranoside (18),39 and methyl 4,6-0benzylidene-2,3-O-di-ferf-butylstannylene-a-~-mannopyranos~de (24)39are dimers, whereas methyl 4,6-O-benzylidene-2,3-O-dibutylstannylene-a-~mannopyranoside is a pentamer. Figures 5 and 6a show crystal structures of 1642and 17,60while Fig. 6b shows a partial crystal structure of 21a.5’

FIG.5.-A segment of the structure of polymeric 2,2-dibutyl-l,3,2-dioxastannane.(16). (From T. B. Grindley, R. Thangarasa, P. K. Bakshi, and T. S. Cameron, Can. J . Chem., 70 (1992) 197-204. with permission.)

28

T. BRUCE GRINDLEY c22

42

FIG.6a.-A view of the structure of methyl 4,6-0-benzylidene-2,3-O-dibutylstannylene-aD-glucopyranoside (17), showing both positions for one of the butyl carbons, which is disordered. (From T. S. Cameron, P. K. Bakshi, R.Thangarasa, and T. B. Grindley, Can. J . Chem., 70 (1992)1623-1630.)

Several aspects of these structures can be used to explain the chemistry of dibutylstannylene acetals. First, in polymers or extended oligomers with octahedral tin atoms, all 02Sn2four-membered rings lie in the same plane. Stannylene actetal rings formed from two oxygen atoms attached to the same tin atom lie roughly in this plane. Stannylene acetal rings on alternate tin atoms in the oligomer extend outwards in opposite directions in the 02Sn2-definedplane, so that the stannylene acetal rings on every second tin atom project outwards on the same side. Large substituents in the plane of the stannylene acetal rings on every second tin atom hinder formation of oligomers higher than a dimer. When the oxygen atoms involved in stannylene acetal formation are both in equatorial orientations on a pyranose ring, the ring forms a large substituent that hinders formation of higher oligomers. However, when the two oxygen atoms forming the stannylene acetal are equatorial and axial, as in a stannylene acetal obtained from a cis-diol, the pyranose ring and its substituents are projected orthogonally to the 02Sn2-definedplane. Higher oligomers are possible and have been observed5' for 21a.

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

29

Another important factor for regioselectivity is that the butyl groups lie approximately perpendicular to the plane defined by the 02Sn2ring(s). In the structure of 17,the butyl groups on tin are highly mobile, even in the crystal at -70°C,60 and an earlier room-temperature determination was unable to locate three of these carb0ns.5~Formation of the dimer requires that one oxygen atom become tricoordinate while the other remains dicoordinate. The tricoordinate oxygen atoms are attached to two tin atoms, each bearing highly mobile butyl groups that hinder approach of electrophiles and decrease reactivity. Branching of the alkyl groups on tin also reduces reactivity in general.20 The third important aspect of these structures is related to the geometries of the dimers or terminal units of oligomers of stannylene acetals (Figs. 5, 6a, and 6b).40*59,60 The tin atoms adopt a distorted trigonal bipyramidal geometry with the alkyl groups in equatorial orientations. The tricoordinate

FIG.6b.-A view of an ATOMS diagram of the part of the X-ray crystal structure of methyl 4,6-O-benzylidene-2,3-O-dibutylstannylene-cr-~-mannopyranoside (2111) that contains ~ first monomeric unit is on the first three monomeric units of the pentameric s t r u c t ~ r e ?The the right. Tin atoms are solid black circles, oxygen atoms are unfilled circles, carbon atoms are intermediate with those in the butyl groups being lighter.

T. BRUCE GRINDLEY

30

oxygen atoms are equatorial to one tin atom but apical to the other. The dicoordinate oxygen atoms are apical, and this may contribute to their reactivity? As with the trialkyltin ethers, these compounds are less aggregated in solution. For instance, 2,2-dibutyl-1,3,2-dioxastannolane (lo), a polymer in the solid has been shown by variable-temperature '19Sn NMR spectroscopy to be a mixture of dimers, trimers, and tetramers in solution, with dimers predominating at room temperature and a b o ~ e . 3 * *This ~~~~' technique has also indicated that most carbohydrate-derived stannylene acetals are present predominantly as dimers in s o l ~ t i o n . ' ~ - ~Supporting '*~~,~ evidence has been obtained from mass-spectral studies43and by comparison of solid-state NMR spectra with those of solutions.4QSome dibutylstannylene acetals derived from cis-diols contain an observable proportion of higher oligomers; benzyl 4,6-0-benzylidene-2,3-O-dibutylstannylene-a-~mannopyranoside (21b) is present as a mixture of a dimer and a trimer in chloroform-a at -60°C but, in the less polar solvent toluene-& is mainly present as a tetramer at that temperat~re.~' Cyclic 1,3,2-dioxastannolanesor 1,3,2-dioxastannanes show a greatly increased tendency to exist as species containing pentacoordinate or hexacoordinate tin atoms than do acyclic dialkyltin dialkoxides. This tendency is caused by the bond angles imposed on the tin atom by ring formation involving long39,40,42,51,52,59.60 (-2.0 Sn-0 bonds." In the solid, 0-Sn-0 ~ ~six3 ~ ~ + ~ ~ bond angles were observed to be 78-80" for both f i ~ e - ~ ,and ~ o o r d i n a t e ~tin~ .atoms ~ ~ . ~in~five-membered stannylene acetals, and 93.2" for the six-coordinate tin atom in the one six-membered stannylene acetal studied by X-ray crystallography?2 These bond angles are closer to the approximately 90" bond angles needed for trigonal bipyramidal geometry or octahedral geometry of five- and six-coordinate tin, but are much smaller than those in the tetrahedral geometry favored by tetracoordinate tin. The 0-Sn-0 bond angles are forced to have these small values because of the geometry of rings that have two adjacent sides (0-Sn bonds) much longer than the others. In dimers, oligomers, or polymers, the Sn-0 bonds inside the monomer units are markedly shorter, 1.98 to 2.13 A, than those between monomer units, which are 2.23 to 2.27 A if the tin atom is pentacoordinate, or 2.43 to 2.60 A if the tin atom is hexa~oordinate.",~~ Only when a considerable number of large substituents are present do stannylene acetals exist to any extent as the monomer; 2,2-dibutyl-4,4,5,5tetraethyl-1,3,2-dioxastannolane is present almost entirely as the dimer at room temperature in chloroform at 20"C, but the monomer-dimer equilibrium gradually shifts to favor monomer above about 80°C. 2,2-Di-t-butyl4,4,5,5-tetramethyl-1,3,2-dioxastannolane is a monomer at room temperature

A)

."'

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

1, I-Dimer

I ,2-Dimer

31

2,2-Dimer

FIG.7.-Dimers of the dialkylstannylene acetal of l,Zpropanediol,

When the two oxygen atoms involved in the stannylene acetal are diastereotopic, three dimers, two with C, symmetry, can be formed, as shown in Fig. 7 for those obtained from 12-propanediol. Dimers are named by means of the numbers of the tricoordinate oxygen atoms.44Steric effects appear to be the most important factor in determining the relative populations of the three dimers. In particular, stannylene acetals derived from trans-diols with one adjacent axial substituent exist in solution, to the level of detection of ‘19SnNMR spectroscopy, as the symmetric dimer in which the tricoordinate oxygen atom is not adjacent to the axial substituent.44Similarly, dialkylstannylene acetals from carbohydrate-derived terminal 12-diols exist predominantly as symmetric dimers with the primary oxygen atoms tricoordinate (Fig. 8).’9,37

Bu

FIG.8.-The populated dimer of 3-0-benzyl-5,6-0-dibutyMa~ylene-l,2-O-kopropylidenecy-~-g~ucofuranose.”

32

T. BRUCE GRINDLEY

Simple 2,2-dibutyl-l,3,2-dioxastannolanesform solid complexes of monomer units with certain nucleophiles, such as pyridine and dimethyl sulfoxide, that have 1:1 stoichiometry and pentacoordinate tin atoms.h2 Such complexes are less stable for more-substituted stannylene acetals, such as those derived from carbohydrates:2 Unfortunately, the precise structures of these complexes have not yet been defined. Addition of nucleophiles to solutions of stannylene acetals in nonpolar solvents has been found to markedly increase the rates of reaction with ele~trophiles,6~ and transient complexes of this type are likely intermediates. Similar rate enhancements were observed in reactions of tributylstannyl ether^.'^ Tetrabutylammonium iodide was the nucleophile used first,s7but a wide variety of nucleophiles has been used subsequently; tetraalkylammonium halides, N-methylimidazole,'8 and cesium fluoride64s6shave been used the most. Such nucleophilic solvents as N,N-dimethylformamide and ethers probably also act as added nucleophiles. As well as increasing the rates of reaction, in certain cases the added nucleophiles reverse the regioselectivity from that observed in nonpolar solvent^.'^*^^

VI. REACTION TYPES AND CONDITIONS Tributylstannyl ethers and dibutylstannylene acetals react with a wide range of electrophiles, including acyl halides and anhydrides, sulfonyl halides, alkyl halides, triorganosilyl chlorides, sulfur trioxide-amine complexes, phosphorylating agents, halogens, and N-halosuccinimides.The normal reaction path involves formation of a single oxygen-electrophile bond per organotin unit. In general, similar reaction conditions are used for the two intermediates. The solvents used range widely from such polar solvents as methanol, N,N-dimethylformamide, or acetonitrile, to weakly polar solvents such as tetrahydrofuran or dichloromethane, to such nonpolar solvents as benzene, toluene, or benzyl bromide. Reactions with acylating, sulfonylating, sulfating, and silylating reagents are normally performed at room temperature or below. Alkylation requires more vigorous conditions. These reactions were originally performed on the stannylene acetal with the alkylating reagent in DMF at elevated temperatures (45°C for methyl iodide or 100°C for benzyl bromide)66or on the tributylstannyl ether in neat benzyl bromide or ally1 bromide at 80-90"C.67It was then discovered that the presence of added nucleophiles markedly accelerates the reactions, so that alkylation of both tributylstannyl ethers and dibutylstannylene acetals in benzene, which is very slow at reflux with benzyl bromide alone, occurs at a reasonable speed at reflux in the presence of added tetrabutylammonium halide^.^^.^^ Many other nucleophiles are also effective, including N-methylimidazoleh8and

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

33

cesium f l ~ o r i d e . ~Cesium ~ . ~ ~ fluoride . ~ ~ has been used mainly in DMF, and the combination of an effective added nucleophile with a polar aprotic solvent allows benzylation with benzyl bromide to occur efficiently at room temperature. Some reactions follow paths different from the single bond per electrophile sequence. Dibutylstannylene acetals derived from all-trans-diols react with phenoxythiocarbonyl chloride at room temperature in 1P-dioxane to give noncyclic phenylthionocarbonates, but when cis-diols are present, cyclic thionocarbonates spanning the oxygen atoms of the cis-diol are obtained both for pyrano~ides~~ and for furano~ides.~~ Dibutylstannylene acetals have yielded propenylidene acetals on reaction with tetrakis(tripheny1phosphine)palladium and acrolein diacetate, in some cases with excellent regio~electivity.~~ For instancep-glucal, methyl a-D-glucopyranoside, methyl a-D-mannopyranoside, and methyl p-Dglucopyranoside yield the 4,6-0-propenylidene acetals in 89, 85, 83, and 80% yields, respectively, as mixtures of diastereomers at the acetal center. Galactose derivatives give mixtures of 3,4- and 4,6-O-propenylidene acetals.” Hodosi and KovBi: observed that, when free sugars are treated with excess dibutyltin oxide in methanol for extended periods of time at temperatures above 60°C, equilibration of the configuration at C-2 occurs.73This observation led to the efficient formation of 6-0-trityl-~-talosefrom 6-0trityl-D-galactose,but also indicates the need for care in the formation of stannylene acetals from free sugars.73 Before workup of the reaction of the dibutylstannylene acetal of a diol with an electrophile such as an acyl, alkyl, or sulfonyl halide, the product present in nonpolar solvents has a halodibutylstannyl group attached to the nonreacted oxygen atom. This organotin derivative can be cleaved with water or mild acid, but chromatography on silica gel is usually sufficient to remove it. Some research groups have made use of the strong Sn-F bond by washing with fluoride ions. VII. FACTORS THATINFLUENCE REACTION REGIOSELECTIVITY

1. Tributylstannyl Ethers When a polyol is reacted with bis(tributy1tin) oxide, all tributylstannyl ethers are formed and these interconvert readily at the reaction temperat u r e ~ . ~ Ogawa ’ , ~ ~ and Matsui suggested that oxygen atoms of tributyltin ethers that have adjacent oxygen atoms in appropriate orientations to coordinate with the tin atom are activated toward e l e ~ t r o p h i l e s ~specifi~.~~: cally, equatorial oxygen atoms that have an adjacent axial oxygen atom,

T. BRUCE GRINDLEY

34

H

0 -qnBu,

HO HO

OMe I OMe

I .,*'

SnBu,

FIG.9.-Coordination of tributylstannyl ethers.74

or primary oxygen atoms where the tin atom of the tributylstannyl ether can coordinate to the ring oxygen, as shown in Fig. 9. Evidence from "'Sn NMR chemical shifts indicates that tributylstannyl ethers exist in solution predominantly as monomers with tetracoodinate tin atoms. The additional coordination pictured in Fig. 935,36 does not occur to any significant extent with ethereal oxygen atoms, but appears to contribute to a small extent with hydroxyl oxygen atoms, and more so for cis-related hydroxyl groups than trans (see earlier discussion for "'Sn chemical shift evidence). However, such transient species are probable reaction intermediates. The same reactivity preferences are observed in the presence of added n u c l e ~ p h i l e s . In ~ ~one * ~ ~suggested mechanism (Fig. lo), the nucleophile adds to the tetracoordinate tin atom to give a species that dissociates to the reactive species, an oxyanion coordinated to the counterion of the n~cleophile.~' A similar mechanism has been suggested for the effect of added nucleophiles on the mechanism of reaction of stannylene acetak6' In another suggested mechanism (Fig. ll), the added nucleophile acts as an acceptor of a hydrogen bond from a hydroxyl group, enhancing the coordination of the hydroxyl oxygen atom to a tin atom attached to an adjacent carbon36and also increasing its nucleophilicity. Evidence for the latter proposal was obtained from the effects of adding N-methylimidazole on "'Sn NMR chemical shifts. With 1 equiv added, signals were shielded by up to 26 ppm, with the largest shieldings being observed if adjacent O H groups were in a cis relationship. A change in coordination state of tin X

(-1

X:(-) + Bu,N(+)

Pu3 O w o H

P n B Z j Bup+)

u

--+

\

SnBu,

Bu,N(+)

up"

FIG.10.-A mechanism proposed for activation of tributylstannyl ethers by n u c l e ~ p h i l e s . ~ ~

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

35

FIG.1l.-An intermediate proposed for tributylstannyl ether reactions in the presence of N-methylimida~ole.~~

from 4 to 5 would be expected to induce a shielding of 100 to 200 pprn for the Il9Sn NMR signal^.^^-^^ The smaller changes in shifts observed with the addition of 1 equiv NMI (0 to 26 ppm), and the observation that changes in shifts of up to 58 ppm were obtained when 4 equiv were added, indicate that equilibria occur between species having coordinated and noncoordinated tin atoms. The position of the equilibrium must lie very far toward the noncoordinated species with 1 equiv or less of NMI added. Both suggested mechanisms appear plausible for the nucleophile considered; however, the second is not reasonable for nonbasic nucleophiles such as iodide ions, and neither provides an explanation of the regiochemistry observed. Yet, all types of nucleophiles cause similar regioselectivity. The observation of increased rates of reaction for cis-diols over truns-diols68demonstrates that higher coordination of tin must be involved. The similarity of regiochemistry obtained for both basic and nonbasic nucleophiles suggests that the role of the nucleophile is to add to tin so as to produce a five-coordinate tin atom that enhances the nucleophilicity of the stannyl ether oxygen atom. Species incorporating six-coordinate tin atoms appear to have only slightly less stability than those with only five-coordinate tin a t o r n ~ . Thus, ~ ~ . ~a ~ possible explanation of the regioselectivity is that it results from additional coordination of the five-coordinate tin atom to appropriately oriented atoms. More definitive explanations of the regiochemistries of these reactions must await more detailed mechanistic studies. In comprehensive studies of the oxidation of tributylstannyl ethers of methyl glycosides with bromine, Tsuda et al. observed that, as with stannylene a ~ e t a l sdifferent ,~~ regioselectivitieswere obtained from those found for substitution reactions. Methyl hexopyranosides were treated with 2 equiv of bistributyltin oxide in chloroform, and then boiled under reflux for 3 h.77,78It was found that this length of reaction is sufficient to allow all starting material to dissolve, but it is unlikely that all four hydroxyl groups were converted into tributyltin ethers. Certainly, longer reaction times at higher temperatures are required for complete conversion in benzene.18 The solutions were then cooled to 0°C and stirred with 2 equiv bromine until the color had disappeared. Under these conditions, one of the hydroxyl groups is oxidized to a ketone. Oxidation of secondary carbons bearing

36

T. BRUCE GRINDLEY

axial oxygens atoms of cis-diols is favored over reaction either at secondary carbons bearing equatorial oxygen atoms or at primary carbon atom^.^^.^' An additional, but lesser, preference is for oxidation at C-3 for equatorial glycosides and C-4 for axial glycosides. 1,2-O-Isopropylidene-a-~glucofuranose, a terminal 1,2-diol, was oxidized at C-5 in high yield, even though another secondary hydroxyl group is free.77With stannylene acetals, the best explanation for the regiochemistry of oxidation is that it is controlled by the structures of the most highly populated dimers. A similar analysis is not possible here because, under these conditions, neither the extent to which tributyltin ethers form nor the structures of the compounds created have been established. An explanation consistent with the very fast reaction and presumably very early transition state is that the least stable tributylstannyl ether reacts fastest. In a very limited sample, axial tributylstannyl ethers were less populated than equatorial ones, but both types were populated significantly?6

2. Dialkylstannylene Acetals Although the factors that influence the regioselectivities obtained from dialkylstannylene acetals are considerably more complicated than with tributylstannyl ethers, the outcome in most cases is surprisingly similar. The factor influencing regioselectivity in the absence of added nucleophiles will be discussed first. More-specific examples will be dealt with later. However, the most important general trends are as follows. In nonpolar solvents without added nucleophiles, the dibutylstannylene acetals of cis-diols on pyranose rings react much faster than those of trans-diols and give product mixtures that are normally dominated by substitution on the equatorial oxygen atom. However, those derived from mannopyranosides give varying amounts of reaction on the axial oxygen atom, 0-2, under these conditions.18.66In the presence of added nucleophiles, the preference for equatorial substitution is much enhanced. Dibutylstannylene acetals of trans-diequatorial diols flanked by one axial substituent react on the oxygen atom adjacent to the axial substituent, but give mixtures if the adjacent substituents are either both equatorial or both If deoxy centers are present, reaction adjacent to the deoxy center is favored.79Dibutylstannylene acetals of terminal diols normally react preferentially on the primary oxygen atom?' In contrast, oxidation reactions using bromine or N-bromosuccinimide usually give the product of reaction at the inherently less reactive oxygen atom; thus, dibutylstannylene acetals of cis-diols on pyranose rings react at the axial oxygen atom,'6,8' and those of terminal, 1,2-diolsreact at the secondary oxygen atom.76*82

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

37

The causes of the regioselectivity of these reactions are complicated, because acyl and silyl groups can rearrange under these conditions (see later discussion) and because added nucleophiles are also used. To simplify the discussion, p-toluenesulfonylation reactions, performed without added nucleophiles, are discussed first. It has been established that the products of these reactions do not rearrange.'O p-Toluenesulfonylation of dialkylstannylene acetals of terminal 1,Zdiols give mainly the product of reaction at the primary oxygen atom if the alkyl groups are butyl, but the regioselectivity is reversed if the two alkyl groups are replaced by a cyclic hexamethylene group.*' Use of alkyl groups on tin that are larger or more hindered than butyl slows the reaction and also increases the amount of product on the secondary oxygen atom. These results can have only one explanation; regioselectivity under these conditions is related to the structure and reactivity of the dominant species present in solution, the dimers. These compounds exist to the level of detection as one dimer, the one having both terminal primary oxygen atoms tricoordinate, because this dimer keeps the substituent on the secondary carbon atom away from the alkyl groups on tin in the other half of the dimer (see Fig. 7). Tricoordinate oxygen atoms are less reactive than the less-hindered dicoordinate oxygen atoms, which are also in the more reactive apical positions in the trigonal bipyramid at tin. Increasing the bulk of the substituent on tin, or making it less able to avoid steric interactions with the secondary substituent, decreases the proportions of the less populated dimers. In these less populated dimers, the primary oxygen atoms are dicoordinate and reactive. Thus, decreasing their populations increases the amounts of secondary products (see later discussion). Monomers are unlikely to be intermediates in these reactions, because they are much less populated than dimers and because their oxygen atoms would not be expected to be more reactive than those of the dimers. Any gain in reactivity conveyed by decreased steric hindrance to electrophile approach would be offset by the increased electron density on tin that presumably accompanies dimer formation. Since the same considerations apply to oligomer reactions as apply to dimer reactions, and since oligomers are usually much less populated, reactions conducted in the absence of added nucleophiles are discussed only in terms of dimers. Results obtained for trans-diols on pyranose rings are consistent with this conclusion. If only a single symmetric dimer is present in solution, as determined by I "Sn NMR spectroscopy, highly regioselective acylation reactions are obtained in which reaction occurs on the dicoordinate oxygen atoms of the dimer. If mixtures of dimers are present, mixtures of products are observed.44

T. BRUCE GRINDLEY

38

The results of the p-toluenesulfonation and many other reactions can be explained by means of the following kinetic scheme, which applies if one C2 symmetric dimer (Dimer 1) is considerably more populated than the other C2 symmetric dimer (Dimer 3), with the unsymmetrical dimer (Dimer 2) being intermediate in concentration (Fig. 12)?7 The following equations can be described from the scheme in Fig. 12, assuming that all reaction takes place on the dicoordinate oxygen atoms and that the initial products do not rearrange or go back to starting materials:

K I = kl I k-] and K2 = k I k-2

d[P2] I dt

=

+ k22 [Dimer 2][R'X]

(2)

+ 2 k13 [Dimer 3][R'X],

(3)

2 k21 [Dimer l][R'X]

d[Pl] / dt = kI2 [Dimer 2][R'X]

(1)

where K 1 is the equilibrium constant between Dimers 1 and 2; K2 is the equilibrium constant for the equilibrium between Dimers 2 and 3; [Dimer I], [Dimer 21, and [Dimer 31, are the concentrations of these dimers; k2l is the rate constant for reaction of one of the two identical dicoordinate

Product 2a =

.

R

p2n

Product 2 = pz

Product 1 =

R

P1

R

FIG.12.--Scheme showing the reactions of dibutylstannylene dimers in which all reactions occur through the dicoordinate oxygen atoms and in which the initial products, Pla, Plb, PZa, and P2b, do not rearrange (adapted from ref?').

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

39

oxygens in Dimer 1 with R’X; k22and kI2are the rate constants for reaction of R’X with 0 - 2 and 0-1, respectively, of the nonsymmetric dimer, Dimer 2; and kI3is the rate constant for reaction at the two identical 0 - 1 atoms of Dimer 3. It can be assumed that the environments of the dicoordinate 0 - 2 atoms are very similar in Dimer 1 and Dimer 2, and that the environments of the dicoordinate 0 - 1 atoms are very similar in Dimer 2 and Dimer 3. Then, k21= k22 = kZf,and k12 = k13 = klf. If Dimer 1 is much more stable than Dimer 2, k2f [Dimer 21 will be much less than k2f [Dimer 11 so it can be neglected. Similarly,klf [Dimer 31 will be much greater than klf [Dimer 31, so the latter term can be neglected. These assumptions change Eq. 2 and 3 to d[P2] / dt = 2 k2f [Dimer l][R’X]

(4)

k2f [Dimer 2][R’X].

(5)

d[P1] / dt

=

Division of Eq. 4 by Eq. 5 yields d[P2] / d[P1] = 2 (k2f/ klf) [Dimer 11 / [Dimer 21.

(6) Two extreme kinetic situations can arise: (a) Dimer equilibration is much faster than reaction (probably p-toluenesulfonation and alkylation) or (b) reaction is much faster than dimer equilibration (probably oxidation by bromine). When equilibration is much faster than reaction, there is a true equilibrium between the dimers and K1 = [Dimer 21 / [Dimer 11.

(7)

Substitution into Eq. 6 gives d[P2] / d[P1] = 2 (k2f

klf)

(11 Kl)

Thus, under these conditions, regioselectivity will depend on a competition between the rates of reaction from the two types of oxygen atoms modified by the ratio of the populations of the two dimers. When the rates of reaction are faster than equilibration, the concentration of Dimer 2 can be assumed to be in a steady state. Under these conditions, and assuming that k2f Q klf, the following equation can be derived: kl [Dimer 11 = k-, [Dimer 21

+ klf [Dimer 21 [R’X]

or

+ klf [RX]) / k l . [Dimer 11 / Dimer 21 = (k1 Substitution into Eq. 6 gives

(9)

40

T. BRUCE GRINDLEY

If p-toluenesulfonylation occurred under these conditions, the product distribution would depend on [R'X]. Changing the concentration of ptoluenesulfonyl chloride from 0.10 M to 1.2 M did not affect the product ratio in a reaction with a dialkylstannylene acetal of methyl 2,343isopropylidene-D-mannofuranoside.This result provides additional evidence that this reaction and all slower reactions occur under conditions where equilibration is faster than reaction. If reaction is faster than equilibration, k l4 k l f[R'X], and Eq. I0 becomes d[P2] / d[P1]

=

2

(k2f

[R'X]) /

kl,

(I0

that is, the product ratio is determined by whether the major dimer prefers to go to product or to the other dimer. Because product formation is assumed to be fast, the reagent essentially traps the major dimer under these conditions. These are probably the conditions under which oxidations of stannylene acetals by bromine occur, which explains why the products of these reactions are often different than those obtained in other reactions. Rearrangements of initial products have been shown to occur during acylation reaction^^^.^' and may also occur in silylation reactions. Roelens has studied the acylation reactions of noncarbohydrate terminal 1,2-diols carefully and shown that the mechanism of rearrangement shown in the upper part of Fig. 13 applies.53 'H NMR measurements demonstrated that this equilibration occurs rapidly and that the position of equilibrium is highly temperature-dependent, favoring the secondary ester primary tin ether (A) at low temperatures (-44°C)but gradually approaching a 1 : 1 mixture at the highest temperature studied, 57°C.Plots of In K versus 1/T for the equilibrium A F? B give AH" = 17.3 kJ mol-' and A r = 53 J mol-I K-'. These numbers are consistent with greater steric destabilization of the sterically larger complexed chlorohalodibutyltin ether when it is on the secondary oxygen atom, and greater freedom when the smaller group is on the primary oxygen atom. The monoester dibutyltin ethers can then be treated with silylating agents to give, as shown in Fig. 13, monoester silyl ether (C and D), or, in some cases, with oxalic acid to give monoesAs indicated in Fig. 13, reaction of A proceeds at a higher rate than that of its isomer B. Equilibration is generally faster than reaction, and so product mixtures highly biased towards the secondary ester C were often ~ b t a i n e d . ~ ~ . ~ Although this mechanism of rearrangement has not been demonstrated in acylation reactions of carbohydrates, it must operate in situations where formation of the intermediate is facile. This would include terminal 1,2diols and cis-1,2-diols. There is considerable evidence that rearrangements Most likely, occur during benzoylation of carbohydrate terminal 1,2-diol~.~"

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

R

B"

1

Pye2SiCI

R

41

I

I

'''To A

0

/Ph

0-Si

c

M \' e Me

R

FIG.13.-Formation and equilibration of acyl derivatives from the dibutylstannylene acetal of 1 -phenyl-1,2-ethanediol and their subsequent trapping reactions."

rearrangements involving six-membered rings are slower and intramolecular rearrangements probably do not occur for trans-diols. It has been observed that reactions of dibutylstannylene acetals of terminal 1,3-diols, or polyols having primary hydroxyl groups free, with tbutyldimethylsilyl chloride yield primary silyl ethers, even for such compounds as methyl a-D-mannopyranoside, where the expectation (see Table VI) for most reactions is for substitution to occur on a secondary oxygen atom.xs-88These observations probably arise from a very large kinetic preference for reaction with primary oxygen atoms, that is, kI2and k I 3B kZIand KZ2,in Fig. 12, rather than a rearrangement from initially formed secondary silyl ethers. When added nucleophiles are present, reaction almost always occurs at the site that is favored for reaction of the parent di01s.~~ Plots of Il9Sn

42

T. BRUCE GRINDLEY

NMR chemical shifts of 18 as a function of temperature in the presence of added N-methylimidazole were curves towards more shielded values that started at room temperature very close to the chemical shifts in the absence of added N-methylimidazole.The curves reached the same limiting values in the presence of 0.5 to 6 equiv of N-methylimidazole, suggesting that monocoordinated dimers were being formed.” However, reactions of monocoordinated dimers would probably give different regioselectivity than observed. Thus, it seems likely that the reactive intermediates in this case are coordinated monomers, and that the tin-containing intermediates simply magnify the inherent reactivity differences between pairs of oxygen atoms. An alternative suggestion is that the coordinated monomer dissociates to give an oxyanion stabilized by the nucleophile’s counterion, most commonly, tetrabutylammonium or cesium by analogy to the mechanism proposed for activation of tributylstannyl ethers by nu~leophiles.’~ This proposal is summarized in Fig. 14,which also shows the product mixture obtained for methyl (2S,3R)-2,3-dihydroxybutanoate.For this compound, reaction on the oxygen atom of the inherently less acidic hydroxyl is favored. Both anions, E and F, are in equilibrium with the coordinated monomer, and the less populated (but more reactive) anion E reacts to a greater extent, or in other words, the difference in the rate constants for trapping is greater than the difference in equilibrium constants. A reversal of the normal expectation for benzylation regiospecificity of dibutylstannylene acetals has been observed in the cesium fluoridecatalyzed reaction with methyl 4,6-0-benzylidene-2,3-O-dibutylstannylenea-D-glucopyranoside (see Table IV)?l Under all conditions, except in the presence of cesium fluoride, the 2-benzyl ether was favored over the 3benzyl ether by ratios of between 2 and 4 to 1. When the reaction was performed in N,N-dimethylformamide containing cesium fluoride, the 3benzyl ether was preferred by about 2 to 1. Solvent effects probably did not cause this change, because the preference for the 2-benzyl ether was greatest in acetonitrile containing tetrabutylammonium iodide. A possible explanation in terms of the mechanism outlined in Fig. 14 is that the greater Sn-F bond strength allows a greater amount of the coordinated dimer and of the two anionic intermediates, E and F, to form, thus allowing an equilibrium analogous to that pictured in Fig. 14 to occur. With tetrabutylammonium halides, perhaps both the coordinated monomer and the anionic intermediates are extremely unstable and reactive, making the two competing transition states in the final benzylation steps earlier and more reactant-like. Then, the final step is less descriminating and the population differences favoring the more stable anion become dominant in determining regioselectivity. The observations noted in the previous two paragraphs might also be explained using the coordinated monomer as the intermediate. With cesium

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

Bu,

,Bu

Bu B 4 d - cs+

CsF

o/sn\o Me0,C

0/

w

DMF

Me0,C

CH,

' 0

t-/CH,

Bu

F\ I Bu P \, E

Me0,C

Bu

CS'

8"

CS'

,sniF

0-

yo- y o F Me0,C CY

"'

Bu

CH,

I

I

Bnl

Bnl

8"

F\I

Bu

43

P\, 4- Me0,C Y O B C", n

G 55%

,sniF BnO

Me0,C

Bu

Po+ CH,

CSI

H 30%

FIG.14.-A mechanism proposed for the effect of cesium fluoride on the reactions of dibutylstannylene aceta1s.h'

fluoride, reactions are observed to occur on the oxygen atom furthest from the electron-withdrawing group for simple stannylene derivatives, such as 2,3-dihydroxybutanoate derivatives. In a stable coordinated monomer, this oxygen atom is expected to bear a greater negative charge and therefore to be more nucleophilic and more reactive. If the coordinated monomer is very unstable, as when the added nucleophile is NMI or a tetrabutylammonium iodide or bromide, the amount of polarization of the Sn-0 bond in this high-energy transient intermediate could be more important in determing regiochemistry. To this author, the anionic equilibrium explanation seems less likely than the monomer reactivity explanation. Carbohydrate oxyanions are not normally very selective toward alkyl halides, and when conditions are set up where they can be formed in a selective manner, as with phase-transfer

44

T. BRUCE GRINDLEY

catalysisY2they favor reaction adjacent to the anomeric center. However, more conclusive discussions of the causes of these preferences await detailed mechanistic studies. IN REGIOSELECTIVITY VIII. TRENDS

1. Symmetrical Diols and Polyols One of the most valuable properties of stannylene acetals derived from 1,2- or 1,3-diols is that in reaction with electrophiles, monosubstituted products are obtained much faster than disubstituted products. This selectivity has been used to advantage many times to break the symmetry present in simple symmetrical diols or polyols, as shown in Table 111.2.'2.65.69,93-1w Some examples are shown in Figs. 15 to 19 (page 48). In later work, Mash and co-workers have shown that 1,n-diols can be converted to mono-0benzyl derivatives in reasonable yields."' The examples in Figs. 17 and 18 are particularly interesting. In Fig. 17Y4*y6 monosubstitution of the dibutylstannylene acetal of a rneso-diol or -trio1 by a chiral acid chloride affords two diastereomers in very unequal amounts, and thus the one reaction both gives monoprotection and creates chiral intermediates. In the example in Fig. 18, 2 equiv of the dibutylstannylene acetal of a symmetrical diol were treated with 1equiv of 1,2-dibromoethane to give the product of monosubstitution of each diol. This reaction only works effectively with 12-dibromoethane if electron-withdrawing groups are present on the diol, but any type of diol yields 2: 1 products with 1,3dibromopropane. loo

2. trans-Diols and Polyols Containing Only trans-Diols This section discusses reactions of compounds containing rrans-1,2-dioI units that are not adjacent to deoxy centers. Compounds having the diol adjacent to a deoxy center are considered in Section VIII,4. Table IV contains a list of the reactions performed on the organotin derivatives of trans-1,2-diols. The table and the following discussion are organized in terms of the structures of the compounds containing the diols: Diequatorial trans-diols are first, followed by the few entries for diaxial trans-diols. Within the first category, the table is arranged in terms of the groups flanking the trans-diol unit: Compounds having one axial and one equatorial group are listed first, followed by those with two equatorial groups, and then by those with two axial groups. Pentopyranosides have been classified according to the regioselectivity they exhibit in reactions: a-Xylopyranosides react mainly at 0 - 2 and their reactions are included in this section; 0xylopyranosides react mainly at 0-4and have been included in the deoxy

TABLE I11 Reactions of Dibutylstannylene Acetals of Symmetrical Diols to Give Monosubstituted Products Reaction Conditions Diol or Polyol

Solvent

Nuc."

Temp. ("C)

Electrophile

Yield

Ref.

65% 79%h 50%'

101 94 2

1.2-Ethanediol cis-1,2-Cyclopentanediol cis- and truns-l,2-Cyclohexanediol

Toluene Toluene CH2C12

Amb.

Benzyl bromide d-Ketopinic acid chloride Bromine

truns-l,2-Cycloheptanediol

CHzC12

Amb.

Bromine

100%'

cis-l,2-Cyclododecanediol

Toluene CH2CI2

0 Amb.

d-Ketopinic acid chloride Bromine

90%d

(R.R)-2,3-Butanediol

94 95

23-Butanediol

CHCI,

Amb.

Benzoyl chloride

100%

93

2.3-Butanediol

CHC13

Amb.

Tosyl chloride

100%

93

(S,S)-Butanediol rneso-Dimethyl tartrate (R,R)-Dimethyl tartrate

2-Chloroethanol Toluene DMF

CsF

140 0 Amb.

2-Chloroethanol d-Ketopinic acid chloride Benzyl iodide

93%f 80%g 99%

100 94 69

(R,R)-Dimethyl tartrate

DMF

CsF

Amb.

Benzyl iodide

85%

69

(R,R)-Dimethyl tartrate

DMF

CsF

Arnb.

p-Nitrobenzyl bromide

93%

69

(R,R)-Dimethyl tartrate

DMF

CsF

Amb.

Ally1 bromide

98%

69

111 0

2

(continues)

TABLEI11 (Continued) Reaction Conditions Diol or Polyol

(R,R)-Dimethyl tartrate (R,R)-Dimethyl tartrate (R,R)-1,2-Divinyl-1,2-ethanediol meso-1.2-Diphenylethan 1,2:5,6-Di-O-isopropylidene-D-mannitol

&

Solvent

Nw'

Toluene 2-Chloroethanol DMF CH2C12 DMF DMF

Temp. ("C)

110 170 110 0 100 i

Electrophi

Yield

Ref.

1,2-Dibromoethane (0.5 equiv) 2-Chloroethanol Benzyl bromide d-Ketopinic acid chloride Benzyl bromide Propargyl bromide

95% 78%h 77% 89%' 76% 70%

100 100 99 94 99 102

Benzyl bromide 1-Bromohexadecane (-)-Camphanic acid chloride Benzyl bromide Benzyl bromide

69% 86% 78W 58% 82%

101 103 96 101 12

1,3-PropanedioI

/-

==t

OH

L H Glycerol l,4-Butanediol

Toluene DMF CH2C12-THF Toluene DMF

CsF

CsF

111 amb. - 100 111 amb.

d

4:

,d

47

T. BRUCE GRINDLEY

48

P h y O H

1. B $ h O -benzene

PhYoH

2. AIlBr, CsF-DMF

Ph

(78%)

FIG.15.-Benzylation

OH

PH Me0,C

Ph

of ( +)-rhreo-hydrobenzoin.Y7

1. Bu2SnO- toluene

*

&CO,Me

+CO,Me Me0,C

I

2. BnBr, CsF-DMF (85Yo)

6H FIG.16.-Benzylation

OBn

of dimethyl L-tartrate. Benzyl iodide gave 99% yield?'

1, Bu,SnO -toluene

Meo2Cgo2 (80%, 90% d.e.)

Hoe

OH

FIG. 17.-Asymmetric

B n O C q , , , , ,OH

acylation of rneso-dimethyl tartrate.Y4

1. Bu2SnO- toluene

I

AOH

BnOCH,

BnOCY+,,,@H

2. BrCH,CH,Br, llO°C, 12h (71%)

FIG.M.-Alkylation

HOqCH*oBn

I

I

c

/b

BnOCH,

P

with 1,2-dibr0moethane.'~

1. Bu,SnO -benzene

uoH 2. Br,-CYCI,

FIG.19.-Oxidation

-0

of cis- and truns-l,2-~yclohexanediol?

8.

"cH,oBn

TABLE IV Reactions of Dibutylstannylene Acetals and Tributyltin Ethers of truns-lJ-Diols

Diol or Polyol

Acetal or Ether

Yield (YO)

Reaction Conditions Solvent

Nue"

Temp ("C)

Electrophile

0-2

0-3

Bromine

95

0

78

0-4

Ref.

Diequatorial Trans-1,2-diols Diols flanked by one equatorial and one axial group

Methyl 4.6-O-benzylidene-a-oglucopyranoside

Ether

Toluene

0

Acetal Benzene

Amb.

Benzoyl chloride

93

0

76

Acetal Benzene

Amb.

Benzoyl chloride

100

0

18

Amb. Amb. Amb. Amb. Amb. 102 Amb. 102 0 100

Benzoyl chloride Benzoyl chloride Benzoyl chloride Tosyl chloride Tosyl chloride Tosyl chloride Tosyl chloride Triflic anhydride Et3N.SO3 Benzyl bromide

72 85 92 70 69 99 87

0 0 0 0

91 10.5 12,13

0

84 7w

0 0 0 0 20

91 106 12, 13 106 107 108

Benzyl bromide Benzyl bromide Benzyl bromide Benzyl bromide

59 89 60 74f

32 10 27 8

108 109 109 110

Acetal Acetal Acetal Acetal Acetal Acetal Acetal Acetal Acetal Acetal

Toluene Benzene Benzene 1,4-Dioxane Benzene 1,4-Dioxane Benzene 1,4-Dioxane DMF DMF/ BnBr 1 : l Ether BnBr Ethefl BnBr Ethef Toluene Acetal BnBr

NEt, NEt, NEt3 NEt, DAMPb NEt3 DMAPb

82 90 90 85

90

10.5

(continues)

TABLE IV (Continued)

Diol or Polyol

Acetal or Ether Acetal Acetal Acetal Acetal Acetal Acetal

Methyl a-D-glucopyranosyl 4.6phenylboronate

Reaction Conditions Solvent Toluene DMF CH3CN DMF Benzene CH3CN

Nuc“ TBAIg

Yield (%)

Temp (“C)

0-2

0-3

41 46 49 25 83

19 13 52

48

18

91 91 91 91 12, 13 91

17

25

91

24

12

111

14

20

91 109 91 78

0

Benzyl bromide Benzyl bromide Benzyl bromide Benzyl bromide Benzyl bromide p-Methoxybenzyl bromide p-Methoxybenzyl bromide p-Nitrobenzyl bromide Allyl bromide Allyl bromide Allyl bromide Benzyloxymethyl chloride Methyl iodide Methyl iodide Methyl triflate Et,N.SO,

54 84 90 79

28 13 8 0

76 110 110 107

0

Benzoyl chloride

85

0

107

50 100 82

TBAIg CsF TBAIR TBAIR

Amb. 50

Acetal DMF

CsF

Amb.

Acetal CH3CN

TBAB~

Acetal Ether Acetal Acetal

DMF Toluene DMF CHICN

Acetal Acetal Acetal Acetal

DMF TCE‘ CHC13 DMF

Acetal Toluene

82

82

100

CSF

0-4

Electrophile

90 Amb. Amb. 45 130 25

42 75 19 70

15

0

rn

40

Ref.

4,6 :4',6'-Di-O-benzylidene-a,atrehalose (27)

ii:

Acetal Benzene

Acetal Acetal Benzyl 4-0-(4,6,-0-benzylidene-a-~Acetal glucopyranosyl-P-oglucopyranoside (28) r-Butyl (ally1 4-0-(4l.6'-0Acetal benzylidene-a-D-glucopyranosy1)P-D-g1ucopyranoside)uronate(29) Acetal Ally1 4-0-(4,6.-0-benzylidene-a-oglucopyranosyl)-6-O-tbutyldimethylsilyl-P-Dglucopyranoside (30) Acetal Methyl 3',4'-0-isopropylidene-alactoside (31) Ether Methyl 6-chloro-6-deoxy-a-~glucopyranoside Methyl 4,6-O-benzylidene-P-oEther galactopyranoside Acetal Acetal Acetal Benzyl4,6-0-benzylidene-&oAcetal galactopyranoside Acetal Acetal Acetal Methyl 4,6-O-isoproylidene-~-ogalactopyranoside Methyl P-D-galactopyranosyl 4,6Acetal phenylboronate Acetal

Et3N

Amb.

Palmitoyl chloride

Et3N

Amb. 0 Amb.

Stearyl chloride Et3N'SO:, Me3N.S03

51 90 (2.2') 87 (2')

0 0

112 107 113

THF

Amb.

Me3N.S03

54 (2')

0

113

THF

Amb.

Me3N.S03

56 (2')

0

113

CH3CN

Amb.

Bromine

64

0

114

Benzene

Amb.

Benzoyl chloride

100

0

18

0

89

78

15 5

72 77 77 72

110 110 110

10

95 55

76 63

Benzene DMF THF

CHCI:,

0

BnBr

TCE' DCE* Benzene Benzene Benzene DMF Toluene DMF

TBAIg

Bromine

85 130 25 Amb.

Benzyl bromide Methyl iodide Methyl triflate Bromine

Amb. 80

Benzoyl chloride Benzyl bromide

66

6 0

0

112

76

0

Et,N.SO:,

0

89

107

0

Benzoyl chloride

0

86

107

Et,N.SO,

0

85

107

25

(continues)

TABLE IV (Continued) ~~~

Reaction Conditions

4-

Diol or Polyol

VI

N

Etner Solvent - __ Acetal Benzene

2-Azidoethyl @-D-galactopyranosyl 4,6-phenyiboronate Octyl 4-deoxy4fluoro-@-~Acetal galactopyranoside Ethyl 4,6-0-benzylidene-l-thio-fl-~- Acetal galactopyranoside Phenyl 4,6-0-benzylidene-l-thio-@-~- Acetal galactopyranoside Methyl 4’,6’-0-benzylidene-@-~- Ether lactoside (32) 2-(Trimethylsilyl)ethyl4’,6’-0Acetal benzylidene-@-lactoside(33) Acetal 1,2-(1-Methoxyethy1idene)-@-Lrhamnopyranose 1,2-(I-Methoxyethy1idene)-0-Dmannopyranose

Nuc“

Yield

Temp (“C)

Electrophile

(YO)

0-2

0-3

0-4

Ref.

Amb.

Me3N.S03

0

77

0

115

Benzene

Amb.

0

50

W

116

CH2C12

Arnb.

0

69

117

0

70

118

CH3CN

TBABh

82

Benzoyl chloride (2 equiv) Chloroacetyl chloride Benzyl bromide

CH3CN

NMI‘

65

Methyl iodide

23

6 19

0

119

DCY

DMAP~

35

0

120

DMAP~

35

2,3,4,2’ All 0 2,3,4,2’ All 0

3’ 49

DCE’

3’ 87

0

120

Acetal Benzene

TBABh

80

1,l’-(Thiocarbonyl) diimidazole Thiophenoxythiocarbonyl chloride Benzyl bromide

-

93

0

121

Ether

Toluene

TBABh

90

5-Bromo-1-pentene

-

71

0

122

Ether

Toluene

TBABh

40 Amb.

0 0

123 124

CsF CsF CsF CsF TBABh CsF

23 Amb. Amb. 20 70 Amb.

60

125 125 126 127 128 129

12 :5,6-Di-O-cyclohexylidene-myo- Acetal Benzene inositol (34) Acetal Acetal Acetal Acetal Acetal 1,2 :5,6-Di-O-isopropylidene-myo- Acetal inositol (35)

DMF DMF DMF DMF Toluene DMF

Methyl iodide (1s)-Camphanic chloride Butanoyl chloride Benzyl bromide Benzyl bromide Benzyl bromide Benzyl bromide Benzyl bromide

&1

97 72 43 74

Methyl a-D-giucopyranoside

Ether Ether

CHCI, Toluene

Bromine Benzoyl chloride

0

- 10

Ether

Toluene

0

Benzoyl chloride

8

Acetal Acetal Acetal Acetal

1.4-Dioxane 1,4-Dioxane Et3N 1,4-Dioxane Et3N 1,4-Dioxane

Acetal DMF Acetal 1,4-Dioxane DMAP*

Methyl a-o-xylopyranoside

0

Amb. Amb. Amb. Amb. 0 Amb.

Acetal 1,4-Dioxane Acetal 1,4-Dioxane Acetal Ip-Dioxane

100 100 50

Acetal 1,4-Dioxane Acetal 1,4-Dioxane

100 Amb.

Acetal 1.4-Dioxane Acetal 1,4-Dioxane Acetal 1,4-Dioxane

100 100 50

Acetal 1,4-Dioxane

100

77 74

0 3 and4 0 3 and4 0 0 0 0 0

65 6 73" 6 56" 0 0 0 0 0 6 22

107 106

(r

61

0 3and4 0 18 16 15

0 0

131 131 131

41 41

32 0

0" 35

131 70

51 47 50

6 6 12

34 23 28

131 131 131

37

0

28

131

0

Benzoyl chloride Benzoyl chloride Benzoyl chloride Phenoxythiocarbonyl chloride Et3N.SO3 Tosyl chloride

76 7w 594 78'

Benzyl bromide Allyl bromide Methoxymethyl chIoride Methyl iodide Phenoxythiocarbonyl chloride Benzyl bromide Allyl bromide Methoxymethyl chloride Methyl iodide

55 59

38 28

130 130 105 130 70

(conrinues)

TABLEIV (Continued)

Diol or Polyol

m P

Aced or Ether

Solvent

Benzyl a-D-xylopyranoside Acetal Benzene Diols flanked by two equatorial groups Methy 4,6-O-benzylidene-&w Ether CHQ glucopyranoside Acetal Benzene Acetal 1PDioxane Acetal 1.4-Benzene Acetal 1.4-Benzene Acetal BnBr Acetal Benzene Acetal CH3CN

Benzyl 4,6-O-benzylidene-P-~glucopyr anoside

Acetal Acetal Aced Acetal

Acetal 2-(Trimethylsilyl)ethyl4.6-0-pAcetal me thoxyenzylidene-P-Dglucopyranoside Ethyl 4,6-O-benzylidene-l-thio-P-~-Acetal glucopyranoside Acetal

Yiild (7')

Reaction Conditions NurO

Temp ("C) Amb. 0

Dh4APb TBABh TBAB"

TBABh

DMF TCEj CHC13 Benzene Benzene Toluene

TJ3AIg

DMF

CSF

Toluene

TBABh

Amb. 102 Amb. 80 85 80 Amb.

0-4

Electrophile

0-2

0-3

Benzoyl chloride

44

0

132

0

90

77

49 0 21 29

39 77 63 61 48 60 21"

Bromine

Re€

33 54

45 130 25 Amb.

Benzoyl chloride Tosyl chloride Tosyl chloride Benzyl bromide Benzyl bromide Ally1 bromide Benzyoxymethyl chloride Methyl iodide Methyl iodide Methyl triflate Benzoyl chloride

22 52 34 53

46 64

133 110 110

37

44

80 Amb.

Benzyl bromide Benzoyl chloride

21 46

55 39

134

Amb.

Benzyl bromide

0

65

135

111

p-Methoxybenzyl bromide

0

72

136

46

66

133

106 133 133 110 133 78

44

Phenyl 4,6-O-benzylidene-l-thio-fl-~Acetal glucopyranoside Acetal Acetal Benzyl 2,3,6-tri-O-benzyl-4-0-(4,6-0benzylidene-0-D-glucopyranosy1)P-D-galactopyranoside (36) 37 Acetal Methyl 4-O-benzyl-P-~Acetal xylopyranoside Methyl 4-O-benzoyl-P-~Acetal xylopyranoside 6,1',6'-Tri-O-tritylsucrose(38) Acetal Ether 39 Acetal Methyl P-D-glucopyranoside Ether Acetal Acetal Acetal p-Nitrophenyl P-D-glucopyranoside Ether Methyl 2-2-0-methyl-6-0Acetal triphenylmethyl-a-Dglucopyranoside Methyl 2-2-0-methyl-6-0Acetal triphenylmethyl-a-Dglucopyranoside Acetal Methyl 3',4'-O-isopropylidene-/3lactoside (40)

DMF

CsF

CH,CN Benzene

TBABh TBABh

Amb.

Benzyl bromide

0

66

135

82 80

Benzyl bromide Ally1 bromide

0 34

61 54

137 138

CC4 Benzene

Amb. Amb.

Bromine Benzoyl chloride

72 48

0 34

139 132

Benzene

Amb.

0

83"

132

Benzene Benzene Toluene TBAF CHC13 1,4-Dioxane 1,4-Dioxane 1,4-Dioxane CHC13 Benzene

Amb. Amb. 80 0 100 50 100 0 Amb.

Chloroacetyl chloride Benzoyl chloride Benzoyl chloride Benzyl bromide Bromine Benzyl bromide Methoxymethyl Methyl iodide Bromine Benzoyl chloride

9 8 0 0 30 35 6 0 -

3'72Y 3'62." 97 97 8 16 10 12 59

140 140 141

Benzene

Amb.

Bromine

-

0

16

CH3CN

Amb.

Bromine

0

50

114

77 131 131 131 77 76

(continues)

TABLEIV (Continued)

Acetnl Diol or Polyol

or Ether

Reaction Conditions Solvent

Noe"

Yield (%)

Temp ("C)

Benzyl 3',4'-O-isopropylidene-pEther Toluene NMS 100 lactoside (41) 3,4-Di-O-allyl-1,2-O-cyclohexylidene- Acetal DMF CsF Amb. D-myo-inositol (42) 3-Deoxy-1,2-O-isopropylidene-4-0- Acetal 1.4-Dioxane DMAP Amb. methyl-2-C-methyl-D-myo-inositol

0-2

0-3

Benzyl bromide

52

0

Benzyl bromide

50

Tosyl chloride

Benzyl bromide

Eleetrophile

0-4

Ref.

0

142

680

-

125, 143

50

682

-

144

5 50

639

-

128

(43) m

VI

1,2 :3,4-Di-O-cyclohexylidene-myo- Acetal Toluene inositol (44) Diok finked by two axial substituents Methyl 4.6di-O-benzyl-c~-~Ether CHCI3 galactopyranoside Methyl 4,6-O-benzylidene-a-~Ether Toluene galactopyranoside Ether Toluene Benzyl 4,6-0-benzylidene-a-~Acetal CHCl3 galactopyranoside Acetal Benzene Acetal Benzene Ether Toluene 1,6-Anhydro-B-~-idopyraranose (45) Diaxial trans-l,2-diols 1,6-Anhydro-~-~-glucopyranose (46) Acetal Benzene Acetal DME Acetal Benzene Ether Toluene

TBAB~

70

0

59

-

78

Benzyl bromide

39

39

-

109

90 Amb.

Ally1 bromide NBS

35 0

35 97"

-

109

Amb. 80 120

Benzoyl chloride Benzyl bromide Benzyl bromide

38 43 20

46 49 50

20

44 44 68

10 Amb. 80

Benzoyl chloride Tosyl chloride Benzyl bromide Benzyl bromide

11 24 18 39

0 65 0 4 8 0 4 0 0 52

145a 145a 145a 68

0

90

TBAIg NMI'

TBAIg NMI'

120

Bromine

82

Methyl 4,6-O-benzylidene-a-~altropyranoside

CHC13

0

Acetal CH,CN

Amb.

Ether

Bromine

0

76

Benzyloxymethyl

0

8

0

53

4

-

78

-

78

32

78

chloride

Methyl a-D-idopyranoside

Ether

CHC13

0

Bromine

" Added nucleophile. 4-Dimethylaminopyridine. ' A second preparation in the same paper using the same method but at 10°C higher temperature gave a 77% yield of the 2-0-benzyl derivative. Ratio of diol to bis(tributy1tin) oxide 1:2.2. ' Ratio of diol to bis(tributy1tin) oxide 1 : 1.8. 'Use of the dihexylstannylene acetal under the same conditions gave an 82% to 2% ratio of 0 - 2 to 0 - 3 products. 8 Tetrabutylammonium iodide. Tetrabutylammonium bromide. ' 1.12,2-Tetrachloroethane. 1.2-Dichloroethane. 1.3-dimethylimidazolidin-2-one. N-Methyhidazole. * Mixture of diastereomers. " Plus 20% 2.6-dibenzoate. " Plus 16% 2.6-dibenzoate. p Plus 2% 2,6-dibenzoate. 9 Plus 5% 6-benzoate and 12% 2.6-dibenzoate. 'Plus 5% 6-ester. ' Plus 23% of a mixture of disubstituted products. ' Plus 10% of the 2.3-di-0-methoxymethyl derivative. " Plus 20% of the 2,3-di-O-methyl derivative. " Plus 14% 2.4-disubstituted product. Plus 16% disubstituted product. From a two-step sequence, the yield was calculated here based on the amount of the first step product that reacted. "The main product involved substitution of the fructofuranose ring, at 0-3' (72% yield). Also 24% at 0-6. na Also 20% at 0-6. Ob The main product was the 6-OMe derivative, 41% yield. Based on starting material consumed.

J

' '

T. BRUCE GRINDLEY

58

center section. For each compound, reactions are roughly organized in terms of speed of reaction, with oxidation reactions followed by acylation, sulfonylation, and alkylation reactions.

phT=&/+ bLp,, HO

0

27

OH

HO

, , T O

0

28 HO

& % O Ph

OH

OBn

-T 0

*& HO

0

29

HO

OH

OAll

Ph-yO

OTBDMS

0

30

& * O

N&/J/-+ HO

HO

31

OMe

HO

OH

OAll

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

59

Ph

4

Lo&

R OHO &‘& HO

HO HO

HO HO

‘I’

OH OH

OR

32 R = M e 33 R = C&C&SiEt,

””

OH

36

BnO um

35

37

OTBS

OH

T. BRUCE GRINDLEY

60

OH

0

HO OH

40 R = M e 41 R = B n

42

HO

OH

43

OH

45

44

/q HO

OH

46

Dibutylstannylene acetals or tributylstannyl ethers derived from isolated trans-diols on pyranose or inositol rings that have one adjacent substituent axial and one equatorial react preferentially on the oxygen atom adjacent to the axial substituent, as shown by many examples in Table IV. Some

APPLICATIONS O F TIN-CONTAINING INTERMEDIATES Ph B'

Ph \

BYo*

1. Bu$nO-toluene

HO

-

2. BzCI- toluene or Er3N.S03-DMF

OMe

so*

R = BZ 85%

61

OMe

R = SO,-+NEt379%

FIG.20.-Benzoylation and sulfation of a dibutylstannylene acetal of a trans-diol containing a phenylb~ronate.'~~

interesting recent examples of this regioselectivity also show that 4,6phenylboronates survive the conditions necessary to form dibutylstannylene acetals (see Figs. 20 and 21). The excellent yields and regiochemistries obtained in esterification reactions performed on this type of dibutylstannylene acetal are emphasized by the use of symmetrical di- and trifunctional acid chlorides, as shown in Fig. 21a.145bJ45c In esterification, oxidation, sulfonation, and sulfation reactions, products are obtained with very high regioselectivity for both acetals and ethers, but alkylation reactions are less regioselective, as shown by numerous examples in Table IV. For benzylation, the greatest preference for reaction next to the axial substituent (about 9: 1) has been obtained by reaction in benzyl bromide as solvent for both tributylstannyl ethers@ '' and for dibutylstannylene acetals,"" with still greater preferences using larger alkyl groups in the dialkylstannylene acetals, such as hexyl or neopentyl groups."' Methylation reac-

Ph

Ph

\

\

"0 I . Bu,SnO- toluene 2. Me3N.S03-

HO

OH

OH

kl FIG.21.-Sulfation 4,6-phenylboronate.'

11%

of the dibutylstannylene acetal of 2-azidoethyl P-D-galactopyranoside Is

62

T. BRUCE GRINDLEY 1. Bu,SnO-PhCH,

x

b

CI

(0.3 eq.), Et,N, .CI 1.5 h, 22 "C

OMe

Ph

FIG.2la.-Formation of a carbohydrate cluster through regioselective esterification using a trifunctional acid ~ h l o r i d e . ' ~ ~ ~ ~ ' ~ ~ ~

tions have normally been performed by treatment of the dibutylstannylene acetal in DMF with methyl iodide at 45°Cto give approximately2 :1 prefere n c e ~ . 'Considerable ~ improvement in regioselectivity has been achieved by performing the reaction in chloroform using methyl triflate as the methylating agent (Fig. 22)."O

1 Bu,SnO

-toluene

2. MeTf-CHCI,

OMe

OMe R1 = Me, RZ = H 90%

R 1= H , Rz = M e 8% FIG.22.-Methylation of a dibutylstannylene acetal under conditions that give improved regioselectivity.""

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

63

An interesting development is the observation that alkylation of dibutylstannylene acetals of this type in the presence of cesium fluoride in DMF gives different regiochemistry than that obtained under all other conditions. For instance, as shown in Fig. 23, the reaction of the dibutylstannylene acetal of methyl 4,6-O-benzylidene-c~-~-glucopyranoside with benzyl bromide yields ratios of 0 - 2 to 0-3 products of 74: 8, 41 :15, and 46: 19, in neat benzyl bromide,110in toluene containing tetrabutylammonium iodide?' and in DMFY1respectively, but 25 :52 in DMF containing cesium fluoride." Similar reversals are obtained in allylation reactions on the same substrate.91J(B The two hydroxyl groups in 1,2 :5,6-di-O-cyclohexylidene-rnyo-inositol (34) and its di-0-isopropylidene analog (35) are trans. The X-ray crystal structure146of the latter compound suggests that the ring is in a skew conformation with the 0-3 and 0 - 4 hydroxyl groups both in axial orienta'~~ that a mixture tions, but NMR studies'29 and ab initio c a l ~ u l a t i o n sindicate of the skew and a chair conformation, with 0-3 and 0 - 4 both in equatorial orientations, is present. Presumably, formation of a dibutylstannylene acetal locks these two compounds in the latter conformation. The reaction of the dibutylstannylene acetal of 34 with an acid chloride gave substitution adjacent to the axial group, as expected for the chair c o n f ~ r m a t i o n . ' ~ ~ Benzylation of the dibutylstannylene acetal of 34 in toluene in the presence of tetrabutylammonium bromide gave about a 1 :1 mixture, but benzylation in the presence of CsF occurred with good (35)129or very good (34)'25-127 regioselectivity on 0-4. Interestingly, acylation with butanoyl chloride in the presence of cesium fluoride also occurred with high regioselectivity on 0-4,lZssuggesting that the reversals of regioselectivity noted in the presence of cesium fluoride in alkylation reactions may occur for all reactions.

phTo+

- phT%&+

1. Bu,SnO - toluene

HO OMe2a. BnBr as solvent, 85 "c

R,O

OMe

2b. BnBr in toluene, TBAI, 50 "C

A R, = Me, R, = H B R, = H, R, = M e

2c.BnBrinDMF,10OoC

2a.AIB 74to8

2b.A/B 41tol5

2d. BnBr in DMF, CsF, amb.

2c. A / B 46 to 19

2d. A / B 25 to 52

FIG.23.-Reversal in the regioselectivity of benzyiation of a dibutylstannylene acetal of a trans-diol in the presence of cesium Buoride?l

T. BRUCE GRINDLEY

64

1. Bu,SnOSnBu,

*oH HO

*;H +

HO

2. BzCI-toluene, -1OC OMe

OMe 1.5 h

73%

BZO

OMe

20%

95%

20 h

FIG.24.-Regioselectivity in the benzoylation of the tributylstannyl ether of methyl glucopyranoside."

(Y-D-

When reactions are performed on tributylstannyl ethers and dibutylstannylene acetals of hexopyranoside derivatives that have more oxygen atoms, including the primary one, unprotected, markedly different results are obtained, as shown in Figs. 24 and 25. Dibutylstannylene acetals favor reaction on the position in the 12-diol unit that is adjacent to an axial substituent, whereas tributyltin ethers prefer to react at the primary centers. However, this pattern was not observed for reactions of the tributylstannyl ether of 1,2-(1-methoxyethy1idene)-P-~-mannopyranose, as shown in Fig. 26.'22 Methylation of this compound through the tributylstannyl ether in toluene in the presence of added tetrabutylammonium bromide also gave substitution on 0 - 3 pred~minantly.'~~ These results may arise from distortion of the chair conformation by the fused isopropylidene acetal. The results obtained for methyl and benzyl a-D-xylopyranosides, where mixtures of 2- and 4-substitution are obtained, reflect two competing trends. The first is for reaction adjacent to the axial glycosyl oxygen. The second, which is discussed further later, is for reaction adjacent to centers that do not bear any substituents, at 0-4 in this case.

- 1,4-diosnne 2b. TsCI, DMAP - 1,4-dioxane 2n. BzCl

R=Bz 0%

76%

R = Ts 22 %

28 %

FIG.25.-Acylation of the dibutylstannylene acetal of methyl cu-D-glucopyranoside.'"."D

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

OH 0

A

HO

FIG.26.-Regioselective ative.lZ2

OMe

1. Bu,SnOSnBu,

HO&o

~

+.OM.

&

2. 5-Bromo-1-pentene, BuJBr, toluene, 90T,120 h

65

71%

alkylation of a tributylstannyl ether of a mannopyranose deriv-

Dibutylstannylene acetals and tributylstannyl ethers of fruns-1,2-diols having both adjacent groups equatorial normally give mixtures of products (see Table IV). However, there are a number of exceptions, and these are discussed here. Dibutylstannylene acetals of rruns-1,2-diols adjacent to equatorial thioglycosides react selectively at 0-3, in contrast to normal glycosides (see Figs. 27 and 28). Very large glycosyl groups cause reaction to occur at 0 - 3 (see Fig. 29). The reaction of methyl 4,6-O-benzylidene2,3-O-dibutylstannylene-~-~-glucopyranos~de with p-toluenesulfonyl chloride in 1,Cdioxane containing 4-dimethylaminopyridine (DMAP) to give only substitution at 0 - 3 in 77% yieldlMmay indicate that it is possible to obtain high selectivity with this substrate in general, if reactions are done in a polar medium with the most effective added nucleophile, namely cesium fluoride. When the tributylstannyl ether of benzyl 3’,4’-O-isopropylidene-Plactoside (41) in toluene containing N-methylimidazole was treated with benzyl bromide, a mixture was obtained in which the 2-benzyl ether was the major product, isolated in 52% yield.14*A study of the alkylation of the tributyltin ether of benzyl P-D-glucopyranosidehas never been reported,

1 Bu,SnO

L

’

“

~

o

O SEt

OH 2a. BnBr, CsF -DMF

2b. p-MeOBnBr, Bu,N+Br - toluene

R = Bn, 65% R = p-MeOBn, 72%

FIG.27.-Benzylation of the dibutylstannylene acetal of the crarans-1,2-diol in ethyl 4,6-0benzylidene-1-thio-P-~-glucopyranoside.’~~.~~~

~

T. BRUCE GRINDLEY

66

1 Bu2Sn0

OMe 2a. BnBr, 85 OC

R2 0 R' = Bn, R2= H 46%. Rl = H, R2= Bn 48%

2b. BnBr, Bu,N+Br-, 80 O C - benzene

R' = Bn, R2= H 29%, RL= H, R2 = Bn 61%

FIG.28.-Benzylation of the dibutylstannylene acetal of the rrans-1.2-diol in methyl 4,60-benzylidene-P-D-glucopyranoside. 110~133

but benzoylation only yields the 6-0-benzoyl d e r i ~ a t i v e Perhaps .~~ alkylation of this compound would occur preferentially on 0-2, by analogy with the lactose derivative. The effects of substituents on 0 - 4 of methyl P-D-xylopyranosides are interesting, as shown in Fig. 30. Replacement of an electron-donating group,

1. Bu,SnO

OH

2. BuBr, Bu,NI - toluene 5 h, 100 "c

39

FIG.29.-Benzylation of a dibutylstannyleneacetal derived from a trans-1,2-diol with two adjacent equatorial substituents, one of which is very large.'41.'5"

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

1 . Bu,SnO -benzene

Ro HO

RO

R20

w

OMe

67

OMe

OR'

OH 2a. R = Bn

Benzoyl chloride

2b. R = B z

Chloroacetyl chloride

R' = Bz, RZ= H 48%, R'

= H,RZ= B n

34%

R' = H,R2 = CICH,CO 83%

FIG.30.-Acylation reactions on dibutylstannylene acetals of 4-0-substituted methyl p-Oxylopyranoside~.'~~

benzyl, by an electron-withdrawing group, benzoate, changed the regioselectivity to favor 0-3 str0ng1y.l~~ The (nonplanar) benzyl group would be expected to hinder the approach of incoming electrophiles more, and so this change could be due either to an electronic effect or to a steric effect, or to some combination of both. The change in regiochemistry already noted when a normal glycoside was converted into a thioglycoside is probably another manifestation of the same effect, which is also evident in later examples. When the truns-1,2-diols are flanked by two axial substituents, mixtures are always obtained, except in oxidation reactions. In the limited number of examples where the truns-l,2-diols would be diaxial if the compound adopted a chair conformation, mixtures are also usually obtained. To form dibutylstannylene acetals, conformational changes to skew, boat, or alternative chair conformations are required. Conversion to the boat is easy for 1,6-anhydro-~-~-glucopyranose'~~ and methyl a-D-idopyranoside, but may be more difficult for methyl 4,6-0benzylidene-a-D-altropyranoside. Formation of di-0- or tri-0-substituted derivatives from tributylstannyl ethers and dibutylstannylene acetals can often be performed regioselec-

SMe

47

T. BRUCE GRINDLEY

68

HO

OH

OH

50

51

tively, as listed in Table V. This procedure has great but underutilized synthetic potential. However, fairly subtle effects are observed, as noted in the examples shown in Figs. 31 and 32 (page 71). Formation of the 2,3di-0-benzoyl derivative shown in Fig. 31 is another example of the effect of electron-withdrawing substituents, since the 2-0-benzoyl derivative is formed first.” Similar selectivity can be achieved with cu-xylopyranosides.’”2 Perhaps the same factor favors reaction with 0 - 4 when the substituent on C-5 becomes powerfully electron withdrawing, as in Fig. 32. Tributylstannyl ethers and dibutylstannylene acetals of @-Dglucopyranosides have been converted into 2,6-di-O-substituted derivatives but it should be in high yields with a wide range of electrophiles,’4J07Js1~’s2 noted that not all conditions result in selective reactions. 2,3,6-Tri-0benzoyl derivatives can also be made in reasonable yield^,'^,"^ constituting presumably another example of the electron-withdrawing substituent effect.

TABLE V Formation of Di- or Poly-0-substituted Derivatives from rrans-Diok

Compound

Acetal or Ether

Methyl 6-chloro-6-deoxy-a-~- Ether glucopyranoside Methyl (methyl 1-thio-(Y-DAcetal g1ucopyranosid)uronate

Yield (YO)

Reaction Conditions Solvent

Nuc”

Benzene Toluene-THF s:4

Et3N

Temp. (“C)

Electrophile

2,4

3,4

Ref.

90

0

0

1%

293

so

Benzoyl chloride

20

p-Methoxybenzoyl chloride

4

49

-

150

Acetyl chloride

0

0

153

Benzoyl chloride

0

Benzoyl chloride Tosyl chloride EtSN.SO3 Benzyl bromide Benzyl bromide Benzoyl chloride Benzyl bromide Benzoyl chloride Benzoyl chloride Benzoyl chloride”

0 0 0 0 2,6 31 0 12 0 0 2,3‘ (69%) 2,3,6,1‘, 6’ 87 2,3,62’, 3‘,6’,73 3,4,6

2,3,6 63 0 0 0 0 3.6 5

2,3,6 40 0 2.6 95 2,6 81 2,682 2,682 4,6 6 2,6 50 2,6 44 0 0

74 74 107 151 75 152 152 132 132 140

(47)

Acetal

Toluene

Amb.

Ether

Toluene

50

Ether Ether Ether Acetal Ether Acetal Acetal Acetal Acetal Acetal

Toluene Toluene DMF BnBr BnBr Toluene Toluene Benzene Benzene Benzene

Sucrose (48)

Ether

Toluene

25

Benzoyl chloride

Trehalose (49)

Ether

Toluene

50

Benzoyl chloride

1,2-O-Isopropylidene-rnyoinositol (SO)

Acetald

CH3CN

82

Benzyl bromided

Methyl a-D-glucopyranoside

Ally1 a-D-giucopyranoside Methyl a-D-xylopyranoside Benzyl a-D-xylopyranoside

6,1’,6’-Tri-O-tritylsucrose (36)

NEt3

TBAB

-5 50 4 85 85 Amb. 105 Amb. Amb. Amb.

40 Acetald

CH3CN

TBAB

82

Ally1 bromided

Acetalb

CH3CN

TBAB

82

Benzyl bromide”

3A6 30 3,6 45

0 0

82

90 c

74

74 74 3,5,6 30 3,5,6 30

-

-

154

-

154

-

154

(continues)

TABLE V (Continued)

Compound Methyl (4-methoxyphenyl @D-g1ucopyranosid)uronate

Acetal or Ether

Yield (YO)

Renetion Conditions Solvent

Acetal

THF

Acetal Acetal Acetal Ether

Benzene Benzene BnBr Benzene

Ether

BnBr

Acetal

Benzene

Acetal Ether

Toluene Toluene

Acetalb

Toluene

Acetal'

Toluene

Nuc" Et3N

Temp. ("C)

Electrophile

23

24

3,4

Amb.

Benzoyl chloride

63

18

Amb. Amb. 85 25

Benzoyl chloride Benzoyl chloride Benzyl bromide Benzoyl chloride

0 0 2,6 56

0 0 3,6 16 3,6 82

4,6 15 4,6 5

105

Benzyl bromide

6 14

3,6 9

4,6 4

80

Benzyl bromide

2,3' 52

-

-

100 100

Benzoyl chloride Benzyl bromidef

3,6 84 2,6 44

3,4 0 0

4,6 0 0

-70

Benzoyl chloride (3 equiv) Benzyl bromide (8 equiv)

1.6,7

(51)

Methyl P-D-xylopyranoside my1 @-D-xylopyranoside Methyl @-D-glucopyranoside 2,2,2-Trichloroethyl 2-deoxy2-~hthalimid0-@-0glucopyranoside 2,2,2-Trichloroethyl2-deoxy2-phthalimido-b-0glucopyranoside Benzyl 4',6'-O-benzylidene@-lactoside(32) 52 Benzyl 3',4'-0isopropylidene-P-lactoside (41) Castanospermine (53)

89

155 132 132 151

156

TBAB

NMI

156 157 134

142

Added nucleophile; for abbreviations, see Table IV. Two equivalents. Also 29% 2-benzoate. Excess reagents. '2.4 plus 3,4. With excess benzyl bromide for 3.5 days. Rearranged product, 15%. a

-

80

Ref.

TBAB

111

60 1,6,7 50

1,6.8 15

158

g

158

APPLICATIONS O F TIN-CONTAINING INTERMEDIATES

71

I . Bu,SnO

BzO

Ho%HO OMe

2. Benzoyl chloridebenzene, 50°C

OMe 90%

FIG.31.-Di-O-benzoylation of the dibutylstannylene acetal of methyl 6-chloro-6-deoxya-o-glucopyranoside.'X

I . Bu,SnO

HO

___)

-k

RO

HO

HO

OR

SMe

47

SMe chloride, Et,N, 20°C toluene, T H F 5:4

4%

SMe

R =p-MeOBz

49%

FIG.32.-Di-O-p-methoxybenzoylation of the dibutylstannylene acetal of methyl (methyl l-thio-a-~-glucopyranosid)uronate.'~~

3. cis-Diols and Polyols Containing cis-Diols Table VI contains information about the very large number of reactions performed on tributylstannyl ethers and dibutylstannylene acetals of cis1,2-diols or polyols containing such a component. The reactions of most diols or polyols adjacent to deoxy or unsubstituted centers are listed in Table VIII; however, those containing an equatorial oxygen atom in a cisdiol next to the deoxy center are listed here, on the basis that the cisstereochemistry is more important in the control of the reaction regiochemistry. The table is arranged to have reactions performed on pyranose derivatives in the 4C1conformation having the gulacro configuration first, followed by those performed on pyranose derivatives in the 4C1conformation having the manno configuration, and then by those on other compounds, divided into several categories. Within each section, /3 anomers are listed before a anomers; then for each type of anomer, the compounds are arranged in order of increasing numbers of hydroxyl groups free. Within each of these categories, 0-glycosides are followed by S-glycosides and then by other glycosides.

TABLE VI Reactions of Dibutylstannylene Acetals and Tributyltin Ethers of cis-Diols

AcetPl Compound

or Ether

Reaction Conditions Yield (%) Solvent

Nuce

Temp. ("C)

0-2

0-3

Amb. Bromine

-

0

75

76

Amb. Benzoyl chloride 80 Benzyl bromide 45 Methyl iodide

-

74 87 >63*

0 0 0

76 63 161

Benzyl chloride

-

85'

0

162

Et3NaS03

-

(3')83

0

107

Allyl bromide

-

91

0

120

Benzyl bromide

-

3' 81

0

159

-

3' 72

0

159

-

3'60 3' 82

0 0

159 159

Electrophile

0-4 Ref.

Compounds Having the galacto Conjigurntion

i. With only 0 - 3 and 0 - 4 unprotected Benzyl 2,6-di-O-benzyl-P-~galactopyranoside

Acetal Benzene

Acetal Acetal Methyl-2-azido-6-O-benzyl-2-deoxy-f3-Acetal D-galactopyranoside Acetal Methyl (ally1 2-O-acetyl-P-~ga1actopyranosid)uronate (54) Acetal Benzyl 2,3,6,2',6'-penta-O-benzyl-/3lactoside (55) Acetal 2-(Trimethylsilyl)ethyl2,3,6-tri-Obenzyl4-0-(2.6-di-O-benzyl-~-~galactopyranosy1)-P-oglucopyranoside Acetal Allyl 2,3,6-tri-O-benzyl40-(2,6-di-Obenzyl-P-D-galaCtOpyranOSyl)-P-Dglucopyranoside (57) Acetal Allyl 2,3,6-tri-O-benzoyl-4-O-(2,6-di-Obenzoyl-fl-D-galactopyranosyl)-/3-Dglucopyranoside (58) Acetal Acetal

Benzene Benzene DMF

TBAI

Toluene

TBAI

0

DMF Toluene

TBAI

DMF

1,4-Dioxane Et3N

DMF DMF

90

80

100

Amb. Benzoyl chloride

100 60

Benzyl bromide Methyl iodide

1,6-Anhydro-3-0-ethyl40-(2,6-di-O- Acetal DMF ethyl-fi-D-galactopyranosyl)-fi-Dglucopyranoside (59) Benzyl 2-O-benzyl-fi-~-fucopyranosideAcetal CH2C12

TBAB

d

Benzyl bromide

25

Bromine

3' 70

0

163

0

76 160

(60)

Methyl 2,6-di-O-benzyl-l-thio-fi-~- Acetal Benzene galactopyranoside Ethyl 2-O-methyl-l-thio-p-~Acetal DMF fucopyranoside Acetal DMF

TBAB

45

Ally1 bromide

80

0 164

CsF

20

Benzyl bromide

85

0 165

CsF

20

80

0 166

Acetal Toluene

TBAB

p-Methoxybenzyl bromide, NaI AUyl bromide

87

0 167

81

0 168

79

Methyl 2,6-di-O-benzyk~-~galactopyranoside 2,6-di-O-benZyl-CX-Dgalactopyranoside

Acetal 1.4-Dioxane E t a Acetal Acetal Acetal Acetal

DMF DMF DMF DMF 2-0-benzoyld-di-0-benyl-ff-D- Acetal DMF galactopyranoside Benzyl6-O-allyl-2-O-benzyl-a-~- Acetal DMF galactopyranoside Ally1 2-0-(2-a~etamid0-3,4,5-t1i-OEther CHC13 aCetyl-2deo~-~D-glucopyranosyl)-cr-

110

Amb. Benzoyl chloride 100 45 35 100 100

AUyl iodide Methyl iodide Methoxymethyl chloride Benzyl bromide Benzyl bromide

n

83

0 0 0 0 0

100

Benzyl bromide

66

0 172

Trichloroacetyl isocyanate

78

0 173

Benzyl bromide p-Methoxybenzyl chloride 85 Benzyl bromide Amb. Methyl iodide 40 Benzyl bromide

81 92

0 174 0 175

75

0 176

t-Butyldimethykilyl chloride

0

81

72

168 168 169 170 171

mgalactopyranosiduronamide (61) Ally1 2-O-methylu-~-fucopyranoside Acetal Methyl 2-O-allyl-a-~-fucopyranoside Aced Methyl 2-O-benzyl-cu-~-fucopyranoside Acetal Acetal Ethyl 2-O-benzyl-l-thio-a-~Acetal fucopyranoside Methyl 2,6-dideoxy-a-~-lyxoAcetal hexopyranoside (62)

Benzene

TBAB

Benzene

TBAI TBAI TBAF

Toluene Benzene DMF Toluene

CSF TBAB

80 80

80

83

o in

85

0

85

0 178

176

TABLE VI (Continued) Reaction Conditions Compound

Acetnl or Ether

Yield (%) Solvent

Noc"

Temp. ("C)

Eledrophile

0-2

0-3

0-4 Ref.

-

89

0

179

98

0

180

Compounds Having the galacto Configuration

2

Acetal Methyl 6-O-benzyl-2-deoxy-ru-~-lyxohexopyranoside Methyl 6-O-t-butyldimethylsilyl-2Acetal deoxy-a-D-lyxo-hexopyranoside(64) Allyl 6di-O-benzyl-2-0-( 1-but-2-eny1)- Acetal a-D-galactopyranoside (65) Allyl 2-O-benzoyl-6-di-O-benzyl-cr-~-Acetal galactopyranoside i i With more than two hydroxyl groups free Benzyl 2-O-benzyl-P-~galactopyranoside D-Galactal p-Methoxybenzyl 6-0-zbutyldimethylsilyl-P-Dgalactopyranoside 6-O-~-Butyldimethylsilyl-4-0-(6-0-rbuty ldimethylsilyl-P-Dgalactopyranosy1)-D-glucal

Toluene

TBAB

80

Benzyl bromide

Toluene

TBAB

80

Benzyl bromide

DMF

100

Benzyl bromide

-

82

0

181

DMF

100

Benzyl bromide

-

90

0

181

80

Benzyl bromide

-

68

0

63

-

70 92

0

0

0

182 183

-

Acetal Benzene

TBAI

Acetal Benzene Acetal THF

TBAB

Ether

Benzene

TBAI

80

Benzyl bromide

0

3'96

0

182

1,6-Anhydro-4-0-(6-0-tntyI-P-~- Acetal Toluene

TBAI

95

Allyl bromide

0

3' 62

0

184

galactopyranosyl)-@-D-glucopyranose (66)

80 p-Methoxybenzyl chloride Amb. Me3N.S03

Acetal THF p-Methoxybenzyl 2-acetamido-6-0benzyl-4-(2,3,4-tri-O-benzyl-a-~fucopyranosyl)-2-deoxy-3-0-( 6-0-rbutyldimethylsilyl-P-Dgalactopyranosy1)-P-Dglucopyranoside (67) Ally1 2,6-di-O-benzyI-4-(2,3,4-tri-O- Acetal Benzene benzyl-a-~-fucopyranosyl)-3-0-( 6-0benzyl-~-D-galactopyranosyl)-P-Dglucopyranoside (68) Acetal DMF Methyl P-L-fucopyranoside Acetal BenzenePhenyl 6-O-benzyl-l-thio-P-~THF galactopyranoside Ether CHC13 Methyl P-D-galactopyranoside Acetal Dioxane Acetal THF Acetal DMF Acetal 1,4-Dioxane Acetal Benzene Acetal Benzene Acetal Dioxane Acetal Benzene Octyl P-D-galactopyranoside Acetal Benzene Acetal Benzene 2-(Trimethylsilyl)ethylP-Dgalactopyranoside Acetal Benzene Benzyl P-D-galactopyranoside Acetal Benzene p-Methoxybenzyl P-D-galactopyranoside Acetal THF Allyl 2-acetamido-2-deoxy-~-lactoside Acetal Benzene

0

3' 94

0 183

0

3' 52

0 185

Methyl iodide Dibenzyl phosphorochloridate 0 Bromine Amb. Benzoyl chloride Amb. Me3N.S03 0 Et3N.SO3 100 Benzyl bromide 80 Benzyl bromide 60 Allyl bromide 50 Methoxymethyl chloride 80 Benzyl bromide 60 Allyl bromide 80 Allyl bromide

0 0

10 51

0 186 0 185

0 0 0 0 0 0 0 0 0 0 0

19 53 93 37 95 65 79 93 60 60 70

Benzyl bromide Allyl bromide Me3N.SO3 Allyl bromide

0 0 0 0

67 85 92

TBAB

80 80 Amb. 80

3' 48

0 63 0 63 0 183 0 191

TBAB

80

Allyl bromide

0

3' 56

0 191

Amb. Me3N.S03

63

Dibenzyl phosphorochloridate

65 63

TBAI TBAI TBAI TBAI TBAB TBAI TBAI

(69)

Allyl 2-phthalamido-2-deoxy-P-lactosideAcetal Benzene (70)

48

77 ff 130 0 113 0 187 0 131 d 188 0 189 0 131 0 116 0 116 0 190

(continues)

TABLE VI (Continued)

Reaction Conditions Compound

Aced or Ether

Yield ( O h ) Solvent

Nuc”

Temp. (“C)

Electrophile

0-4 Ref.

0-2

0-3

0 0 0 0 0 0 0

3’70 3’ 70 3’54 3’61 3’ 71 3’63 0

0 0 0 0 0 0 6’92

192 191 119 1W 193 194 86

2’ 0

3’ 77

0

195

0

3‘80

0

183

2’ 0

3‘ 85

Compoundr Having the galacto ConFguratwn Methyl &lactoside (71)

4

a

Benzyl P-lactoside (72) 2-(Trimethylsilyl)ethylP-lactoside (73) p-Allyloxybenzyl P-lactoside (74) .l-Pentenyl~-Iactoside(75) p-Methoxybenzyl 2-acetamido-4,6-0benzylidene-2-deoxy-3-0-(@-~galactopyranosyl)-P-oglucopyranoside (76) p-Methoxybenzyl 2-acetamido-6-0benzyl4-(2,3,4-tri-O-benzyl-a-~-

Acetal Acetal Acetal Acetal Acetal Acetal Acetal

Benzene Benzene CH3CN Benzene Benzene Toluene THF

TBAI TBAB TBAB TBAB TBAB TBAB

Acetal Benzene

TBAB

Acetal THF

p-Methoxybenzyl chloride Ally1 bromide Methyl iodide Ally1 bromide Allyl bromide d Allyl bromide Amb. t B u tyldimethylsilyl chloride 80 Allyl bromide 80 80 45 80 80

Amb. Me3.SO3

fucopyranosyl)-2-deoxy-3-0-(~-~galactopyranosyl)-@-Dglucopyranoside (77) 1,6-Anhydro-4-0-(8-~Acetal CH$N galactopyranosyl)-2,3-O-benzylideneP-D-mannopyranose (78) Acetal THF Ethyl 1-thio-P-lactoside (79)

NMI

80

Ally1 bromide

Amb. t-Butyldimethylsilyl chloride

0

0

4’ 0 1%

6‘96

86

Phenyl 1-thio-a-lactoside (80)

4

Acetal THF Acetal 1,4-Dioxane Phenyl 2-acetamido-2-deoxy-l-thio-a- Acetal THF lactoside (81) Ethyl 1-thio-&D-galactopyranoside Acetal Benzene Methyl 1-thio-8-D-galactopyranoside Acetal THF Phenyl 6-O-benzyl-l-thio-p-DAcetal Benzenegalactopyranoside THF 82 Acetal THF Methyl a-L-fucopyranoside Acetal Toluene Acetal Toluene Acetal DMF 2-(Trimethykilyl)ethyl 4-o-(a-DAcetal Benzene galactopyranosyl)-&Dgalactopyranoside (83) Ether CHC13 Methyl a-D-galactopyranoside Acetal 1.4-Dioxane Acetal 1PDioxane A c e d 1,4-Dioxane Acetal DMF Acetal Toluene Ally1 a-D-gdactopyranoside

TBAB

66 Tosyl chloride Amb. Me3N-S03 Amb. Mefi.S03

0 0 0

75% 7Sh 3' 83

0 113 0 113 0 113

TBAB

63 Ally1 bromide Amb. 1-Butyl bromoacetate 63 Dibenzyl phosphorochloridate 82 Allyl bromide 65 Benzyl bromide 65 Ally1 bromide 65 Methyl iodide 80 Ally1 bromide

0

60 65 51

0 197 0 198 0 185

65 93'

0 198

Et3N TBAI TBAI TBAI TBAB

0 100

TBAI

50 90

TBAI

65 60

Bromine Benzyl bromide Methoxymethyl chloride p-Methoxybenzyl chloride Methyl iodide Crotyl bromide

0 0

0

0 0

8(y'

0 0

70 3' 63'

0 0 0 0 0 0

0 71 90 60J

70 *61

0 0

11 11 0 186 0 190

70

77

0 131 0 131 0 199 0 186

om

Compounds Having the manno Configuration i Only 0-2 and 0-3unprotected

Methyl 4,6-O-benylidene-a-~mannopyranoside

Acetal 1.4-Dioxane E t a Aced ACetal Acetal ACetal ACetal Acetal Acetal

Benzene Benzene NMI DMF 1ADioxane DMAP DMF DMF DMF

Amb. Benzoyl chloride Amb. Amb. 0 Amb. 100 100 45

Benzoyl chloride Benzoyl chloride EtJN.SO3 Tosyl chloride Benzyl bromide Allyl iodide Methyl iodide

Major Minor

- 66 -

85

15

0 70 0 0

9 0 14 9 7 8 5 79 76 -

0

0

18 18 107 107 201 201 201

(continues)

TABLE VI (Continued) Reaction Conditions Acetal

Yield (%)

or

Compound

Ether

Solvent

Nuc."

Temp. ("C)

Electrophile

0-2

0-3

0-4 Ref.

Compounds Having the manno Configuration CPentenyl 4,6-O-benzylidene-a-~mannopyranoside Methyl 4,6-di-O-benzyl-a-~mannopyranoside

Methyl 4-O-benzyl-a-~rhamnopyranoside Methyl-4-O-benzyl-cu-Lrhamnopyranoside Benzyl 4-O-benzyl-a-~rhamnopyranoside

Acetal DMF

95

Acetal THF Acetal Acetal Acetal Acetal

Benzene THF Benzene Toluene

Acetal Toluene Acetal Benzene

Benzene DMF Benzene DMF

Methyl 4-O-methyl-a-~rhamnopyranoside Allyl 4-O-methyl-a-~Acetal Benzene rhamnopyranoside Allyl 4-0-acetyl-a-L-rhamnopyranoside Acetal Benzene AUyl 4-O-benzyl-a-~-rharnnopyranoside Acetal DMF

0

59

-

202

9

67

-

203

41 10 18 10

59 74 82 86

- 203 - 203 - 203 9

0 0

95 90

9 - 204

Amb. Benzoyl chloride

24

66

-

80 Amb. 80 100

32 0 35 0

53 88 54 62

- 205 - 206 - 205 - 207

Amb. Benzoyl chloride

TBAB TBAB TBAI

Amb. Amb. Amb. 90

TBAI TBAI

40 80

Acetal Benzene Acetal Acetal Acetal Acetal

Benzyl bromide

TBAB CsF TBAB

Benzoyl chloride Tosyl chloride Tosyl chloride Benzyl bromide Methyl iodide Methyl iodide

Benzyl bromide Benzyl bromide Allyl bromide Benzyl bromide

205

TBAB

80

p-Methoxybenzyl chloride

0

94

-

208

TBAB

80 90

p-Methoxybenzyl chloride p-Methoxybenzyl bromide

0 0

74 83

-

208 209

-

Methyl 4-O-r-butyldimethylsilyl-a-~Acetal Benzene rhamnopyranoside Acetal Benzene Benzyl 4-O-r-butyldirnethylsilyl-a-~rhamnopyranoside (S)-2-(Benzy1oxycarbonylamino)propyl Acetal Benzene 4-O-rnethyl-a-~-rhamnopyranoside

TBAB

80

Methyl iodide

20

80

-

TBAB

80

Methyl iodide

20

78

- 21 1

TBAI

80

Methyl iodide

0

Methyl iodide

5

58

- 213

Benzyl bromide

0

95

- 214

Amb. t-Butyldimethylsilyl chloride

0

95

- 215

MajoF'

210

- 212

(84)

p-Nitrophenyl 4-O-benzyl-a-~Acetal rhamnopyranoside Acetal Methyl 4-azido-4,6-dideoxy-a-~mannopyranoside Ethyl 4,6-O-benzylidene-l-thio-a-~- Acetal mannopyranoside Phenyl 4,6-O-benzylidene-l-thio-a-~-Acetal mannopyranoside Acetal

DMF

50

BnBr

100

Acetal Ethyl 4-O-methyl-6-O-benzyl-l-thio-aD-mannopyranoside Acetal Ethyl 4-O-methyl-l-thio-a-~rhamnopyranoside Acetal Ethyl 4-O-methyl-l-thio-a-~rhamnopyranoside Acetal Ethyl 4-O-benzyl-l-thio-a-Lrhamnopyranoside Acetal Acetal Phenyl 4-O-benzyl-l-thio-a-~rhamnopyranoside Phenyl 4-O-acetyl-l-thio-a-~Acetal rhamnopyranoside 4-O-Benzyl-a-~-rhamnopyranosyl azide Acetal

DMF DMF

CsF

Amb. Benzyl bromide

0

86

- 216

DMF

0

94

- 217

DMF

CsF, Amb. p-Methoxybenzyl chloride TBAB CsF Amb. Benzyl bromide

0

80

- 218

DMF

CsF

Amb. Benzyl bromide

0

78

- 219

DMF

CsF

Amb. Benzyl bromide

0

76

-

DMF

CsF

Amb. Benzyl bromide

0

70

- 135

DMF

CsF

0 0

-

220

CsF

Amb. Benzyl bromide Amb. Benzyl bromide

85

DMF

79

-

220

Methyl iodide

0

79

- 221

Amb. AIlyl bromide

0

82

- 222

80

DMF DMF

CsF

219

(conrimes)

TABLE VI (Continued) Reaction Conditions

Yield (70)

Acetal Componnd

or Ether

Temp. Solvent

Nuc"

(OC)

Electrophile

0-2

0-3

0-4 Ref.

Compounds Having the manno Configuration

ii. With more than two hydroxyl groups free Methyl 6-O-triphenylmethyl-cu-Dmannopyranoside Benzyl 6-O-triphenylmethyl-a-~mannopyranoside

Methyl 6-chloro-6-deoxy-a-~mannopyranoside Methyl a-L-rhamnopyranoside

Methyl I-thio-a-t-rhamnopyranoside

Phenyl 1-thio-a-L-rhamnopyranoside 85

Acetal DMF Acetal DMF Acetal Benzene Ether Acetal Acetal Acetal

Toluene Benzene Toluene Benzene

Acetal Acetal Acetal Acetal Acetal Acetal Acetal Acetal Acetal

DME DMF DMF Toluene Benzene Toluene DMF DMF DMF

Acetal DMF Acetal DMF

TBAI TBAB TBAI

TBAI

CSF TBAI TBAI TBAI CsF CsF

CsF CsF

80

Allyl bromide

0

75

0

223

45 80

Methyl iodide Allyl bromide

0 0

75 45

0 0

224 63

Allyl bromide Methoxymethyl chloride p-Methoxybenzyl chloride Benzoyl chloride

1.5 0 0 25

62 45 66

0 0 0 -

57 63 225 18

Amb. Benzoyl chloride 110 Benzyl bromide Amb. Benzyl bromide 65 Benzyl bromide 60 Allyl bromide 65 Allyl bromide 65 Methyl iodide Amb. Benzyl bromide Amb. p-Methoxybenzyl chloride + KI Amb. Methyl iodide 50 Methyl iodide

0 0 0 0 0 0 0 0 0

loo 50 83

0 0

89'

0

45 89' 81 78 56

0 0 0 0 0

18 226 10 11 227 11 186 228 228

0 0

77 68

0 0

160 229

80 Amb. 90 Amb.

60*

Methyl ff-D-mannopyranoside

Allyl a-D-mannopyranoside

Ether Acetal Acetal Acetal Acetal Acetal Acetal Acetal

CHCL 1,4-D)ioxane Toluene TBAI DMF CsF DMF Toluene TBAI DMF DMF

0 Amb. 65 25 75 65 65 65

Bromine Benzoyl chloride Benzyl bromide Benzyl bromide Allyl bromide Allyl bromide Methyl iodide Methyl iodide

91 0 0 0 0 0 0 0

20

Benzoyl chloride

98

0

-

231

20 111 20

Tosyl chloride Benzyl bromide Benzoyl chloride

95 81 81

0 0 0

-

231 231 231

20 111 0 0 80 120 0 120 120 120 120 120 Amb.

Tosyl chloride Benzyl bromide Bromine Bromine Allyl bromide Benzyl bromide Bromine Benzyl bromide Benzyl bromide Benzyl bromide Benzyl bromide Benzyl bromide Benzoyl chloride

83 86 0 0

24

0 231 7 231 0 78 91 8 4 0 78 0 0 232 25 0 68 8 4 0 78 10 83 68 78 10 68 78 22 68 9 0 0 68 0 0 68 66 - 205

80 80

Benzyl bromide Ally1 bromide

32 35

53 54

0

0

78

64.5 85'

d 130

84

0 230

60' 86' 72 73

0 224 0 11 0 186 0 186

0

11

Other Hexopyranose Derivatives Methyl 4.6-O-benzylidene-a-~allopyranoside

2

Methyl 4,6-O-benzylidene-&~allopyranoside

Methyl a-D-auopyranoside Methyl 0-D-allopyranoside

1,6-Anhydro-P-~-mannopyranose (86) Methyl a-D-akropyranoside 1,6-Anhydro-P-~-galactopyranose (87) 1,6-Anhydro-/3-~-allopyranose (88)

1,6-Anhydro-P-~-altropyranose (89) 1,6-Anhydro-P-~-gulopyranose (W) 1,6-Anhydro-P-o-taIopyranose (91) Benzyl4-0-benzyl-6-deoxy-c-~-

Acetal Toluene Acetal Toluene Acetal Toluene Acetal Toluene Acetal Acetal Ether Ether Acetal Ether Ether Ether Ether Ether Ether Ether Acetal

Toluene Toluene CHC13 CHCl3 Benzene Toluene CHCI, Toluene Toluene Toluene Toluene Toluene Benzene

TBAI

TBAI

TBAI NMI

NMI NMI NMI NMI NMI

64 65 0 0 11 0 8

0"

talopyranoside (92) Acetal Benzene Acetal Benzene

TBAB TBAB

-

205 205

(continues)

TABLE VI (Continued) Reaction Conditions Compound

Aced or Ether

Yield (%) Solvent

Nuc."

Temp. ("C)

Electrophile

0-2

0-3

0-4 Re€ ~

~~

Other Hexopyranose Derivatives

Methyl 4-0-benzyl-6-deoxy-c-~talopyranoside (93) Methyl 4-O-benzyl-6deoxy-a-~talopyranoside (94)

Ether

Toluene

TBAI

36

55

-

9

Methyl iodide

0

80

-

233

CSF

Amb. Allyl bromide

0

95

-

143

CsF

Arnb. AUyl bromide

0

94

-

143

CsF

Amb. Amb. 100 70 Arnb.

Allyl iodide Benzoyl chloride Benzyl bromide Benzyl bromide p-Methoxybenzyl chloride, KI Allyl iodide Methyl iodide Allyl bromide

O 0 0 0 0

d 62

-

0 0 0

73 66 83

-

Allyl bromide

0

89

-

Acetal Benzene

90

Benzyl bromide

80

Inositols

3

1,5,6-Tri-O-allyl-4-0-benzyl-myo- Acetal DMF inositol (95) 1,6-Di-0-allyl-4,5-di-O-benzyl-myo- Acetal DMF inositol (%) Acetal DMF 1,4,5,6-Tetra-O-benzyI-rnyo-inositol (97) Acetal Benzene Acetal DMF Acetal Toluene Acetal DMF Acetal Acetal 1,4-Di-O-allyl-5-O-p-methoxybenzyl-6Acetal 0-benzyl-myo-inositol (98) 1,5,6-Tri-O-benzy1-4-0-(2,3,4,6-tetra-O- Acetal benzyhx-D-mannopyranosyl)-L-rnyoinositol (99)

TBAB CsF

DMF DMF DMF

CsF

100 45 20

DMF

CsF

20

82 82

126 234 66 - 128 - 235 66 66 - 236 -

237

1.5.6-Tri-O-benzyl-4-0-(2,3,4.6-tetra-OAcetal DMF

CsF

20

Allyl bromide

0

d

-

237

Toluene

TBAB

70

Benzyl bromide

0

80

-

128

Toluene

TBAB

70

Benzyl bromide

3

60"

-

128

CH3CN DMF

TBAB

82 50

p-Methoxybenzyl chloride AUyl bromide

0 0

d

73

-

238

DMF

50

Ally1 bromide

0

69

-

238

DMF

50

Allyl bromide

0

d

-

238

DMF

50

Allyl bromide

0

62

0

239

benzyl-a-D-mannOpyranOSyl)-D-myoinositol (100)

8

1.45,6-Tetra-O-p-methoxybenzyl-myo- Acetal inositol (101) 1,4,5,6-Tetra-O-benzoyl-rnyo-inositol Acetal (102) 1,4,5-Tri-O-allyl-myo-inositol(103) Acetal 5,6-Di-O-allyl-l,4-di-O-benzyl-myo- Acetal inositol (104) 5,6-Di-O-allyl-l,4-di-O-pAcetal methoxybenzyl-myo-inositol (105) 1,4-Di-O-allyl-5,6-di-O-benzyl-myo- Acetal inositol (106) 1,4-Di-O-benzyl-5,6-O-isopropylidene-Acetal myo-inositol (107) Acetal 1,4-Di-O-benzyl-myo-inositol (108) 1,5,6-Tri-O-benzyl-4deoxy-4-fluoroAcetal myo-inositol (109) 1,5,6-Tri-O-benzyl-4chro-4-deoxyAcetal myo-inositol (110) 1,4-Di-O-benzyl-5,6-O-butanoyl-rnyo- Acetal inositol (111) 1,4~,6-Tetra-O-aUyl-myo-inositol (1U) Acetal 4,5-Di-O-benzyl-l,6-O-cyclohexylidene-Acetal mvo-inositol (ll3) 1,4-Di-O-benzyl-5,6di-O-(l-but-2-enyl)Acetal myo-inositol (114) 4,5,6-Tri-O-benzyl-3-deoxy-~-myoAcetal inositol (115) Hexa-0-diethylboronyl-myo-inositol Ether (116) Ether

Toluene DMF

TBAI

DMF DMF

CsF

0

Allyl bromide Methoxymethyl chloride

0

Methoxymethyl chloride

111

Amb. p-Methoxybenzyl chloride

0

154

0

60 75

0 239 - 240

0

92

- 240

0

85

- 241

0 0

>68 80

- 242 - 243

0

95

- 244

159

20

- 245

+KI d AUyl bromide Arnb. Benzoyl chloride

DMF Benzene CH3CN

TBAB

82 d

DMF-toluene

2-Butenyl (crotyl) bromide Methoxymethyl chloride

Toluene

NMI

Amb. Benzyl bromide

1 56

5 27

246

Toluene

NMI

Amb. Allyl bromide

1 53

522

246 (continues)

TABLE VI (Continued)

Acetal

Reaction Conditions

or

Compound

Ether

Solvent

Nuc"

Temp. ("C)

Yield (YO) Electrophile

0-2

0-3

59

-

69

247

50

56

81

0

81

0-4 Ref.

Compounds Containing cis-1,3-Diols and Deoxy Centers

$2

3-O-benzoyl-1,2-O-isopropylidene-t!3-~-Ether fructopyranose (117) 2,3-O-Isopropylidene-P-~Acetal fructopyranoside (118) 1,2-O-Isopropytidene-P-~Acetal fructopyranoside (119) Acetal Acetal Ether Acetal Methyl 2-0-benzyl-8-Darabinopyranoside Acetal Methyl 0-L-arabinopyranoside Acetal Ether Ether Acetal Acetal Acetal Acetal Ether Methyl P-o-arabinopyranoside Acetal Acetal

DMF

100

Benzyl bromide

Benzene

Amb. Bromine

10

Benzene

Amb. Bromine

5 48

0 0 0 0 70

65P 18 loo 18 100 18 14 248 0 249 72 77 93 77 04 130 23 130 53 106 14 131 21' 131 0 18 39 18 20 18

Benzene Benzene Benzene DMF

NMI

CsF

CsF DMF CHCI, CHC13 Toluene 1,4-Dioxane 1,4-Dioxane DMAP 1,4-Dioxane 1,4-Dioxane Benzene Benzene NMI Benzene

Amb. Amb. Amb. Amb.

Benzoyl chloride Benzoyl chloride Benzoyl chloride Benzyl bromide

-

25 Amb. 0 0 Amb. Amb. 100 50 Amb. Amb. Amb.

Benzyl bromide Bromine Bromine Benzoyl chloride Benzoyl chloride Tosyl chloride Benzyl bromide Methoxymethyl chloride Benzoyl chloride Benzoyl chloride Benzoyl chloride

0

100

0

0 51 49 41 78 60 91 54 80

-

-

0 8 0

0 0 0 0 0

Phenyl a-L-arabinopyranoside

Acetal Ether Acetal Acetal 1,5-Anhydro-l-benzylamino-l-deoxy- Acetal 4,6-~-isopropylidene-~-mannitol (120) (lS,3R,4R,5R)-1,3,4-Trihydroxy-6Acetal oxabicyclo[3.2.l]octan-7-one(121)

1,4-Dioxane Toluene Dioxane 1.4-Dioxane Toluene TBAB

DMFbenzene

Amb. Benzoyl chloride 0 Benzoyl chloride 100 Benzyl bromide 50 Methoxymethyl chloride 100 Benzyl bromide

0 0 0 -

50 69 74 86 75

16 130 W 130 0 131 0 131 - 250

80

Benzyl bromide

-

81

0 251

Benzyl bromide

-

12'

0 252

t-Butyldimethylsilyl chloride

-

65'

0 253

Benzyl bromide

-

81

0 254

-

80

0 255

0

Kdo Derivatives

e

Methyl (methyl 3-deoxy-7,8-0Acetal isopropylidene-cr-~-manno-2octu1opyranosid)onate (U2) Methyl (allyl 3-deoxy-7,8-0Acetal isopropylidene-a-~-manno-2octu1opyranosid)onate (123) Ethyl (ethyl 3-deoxy-7,8-0Acetal isopropylidene-l-thio-~-~-manno-2octu1opyranosid)onate (W) Methyl (allyl 3-deoxy-7,8-0-(1,1,3,3Acetal te traisopropyldisiloxanylidene)-cY-omonno-2-octulopyranosid)onate (125)

Benzene

TBAB

80

Toluene

TBAB

111

DMF

CsF

Amb.

DMF

CsF

Amb. p-Methoxybenzyl chloride

(continues)

TABLE VI (Continued) AWtd or

Compound

Ether

Reaction Conditions Solvent

Nuc.'

Temp. ("C)

Yield (%) Electrophile

0-2

0-3

0-4 Ref.

Furanose Derivatives

Uridine (126)

Acetal Acetal Acetal Acetal Acetal

MeOH MeOH DMF DMF DMF

Etfi Et,N

Amb. Acetyl chloride Amb. Benzoyl chloride 100 Benzyl bromide 37 Methyl iodide ( B U ~ S ~Amb. ) ~ Phosphorus oxychloride

2' 0 2' 0 2'31 2' 39 2' 35

3' 69 3'86 3'26 3'32 3' 52

-

1 1

-

256

1 1

1

0

Thymidine (127) 1'-Cyanothymidine (l28) 1'-Methylthymidine (129) Cytidine (WO) Adenosine (131)

Acetal DMF

TBAB

Acetal DMF

TBAB

Acetal Acetal Acetal Acetal Acetal Acetal Acetal Acetal

THACl THACl THACl Et3N Et3N Eta Et3N TBAB

CH3CN CH3CN CH$N MeOH MeOH MeOH MeOH DMF

Inosine (132) Acetal MeOH (3R,4R,5R)-l-Benzyl-3,4-dihydoxy-5- Acetal DMF (methoxymethoxy)methyl-2pyrrolidinone (133)

Et,N CsF

Amb. o-Nitrobenzyloxymethyl chloride 75 1-(p-Nitrobenzyloxymethyl) pyridinium chloride Amb. Tosyl chloride Amb. Tosyl chloride Amb. Tosyl chloride Amb. Acetic anhydride Amb. Benzoyl chloride Amb. Benzoyl chloride Amb. Tosyl chloride Amb. o-Nitrobenzyloxymethyl chloride Amb. Benzoyl chloride Amb. Benzyl bromide

2' 3' >39 -39% 2' 3' >37 >37 2' 70 3'0 2' 0 3' 70 2' 0 3' 70 2'24 3'72 2' 0 3' 87 2'0 3' 70 2'70 3'0 2' 24 3'some 2' 13 -

3'50

74

- 257 - 71 - 71 - 71 1 1 1 1 - 256

1 12 258

-

Miscellaneous Compounds

134 2'-O-Acetyltylosin (135)

Acetal Toluene Acetal Toluene

cis-3,4-Dihydroxy-2-piperidinone (136)

Acetal Acetal Acetal Acetal

Toluene Benzene Benzene

DMF

TBAI

TBAI

TBAI CsF

80 p-Methoxybenzyl bromide Amb. p-Methoxyphenylacetyl chloride Arnb. Phenylacetyl chloride Amb. Methoxymethyl chloride 80 p-Methoxybenzyl chloride Arnb. Methyl iodide

Added nucleophile; for abbreviations of nucleophile names, see Table IV. A > sign indicates that the yield reported was for more than the minimum number of steps. Partial ester exchange occurred the product contained 55% methyl ester plus 30% benzyl ester. * Not reported. 'Plus 21% of the 3.6-di-0-benzoyl derivative. 'Plus 8% of the 6-0-benzyl derivative. g With 15 equiv p-toluenesulfonyl chloride, 75% at 0-3' and 15% di-product (3' and 6'). With 2 equiv sulfur trioxide-trimethylamine complex, 76% at 0-3' and 10% di-product (3' and 6'). ' Based on starting material consumed. The yield was not improved by performing the reaction in toluene or acetonitrile or in DMF containing cesium fluoride. Ir Plus 10% dibenzoate. Plus 30% of the 3.6-di-0-benzoyl derivative. Only the di-0-benzyl derivative could be isolated. " Plus 20% of three mono-0-benzyl derivatives with the benzoates rearranged. " Obtained as a minor product. p Plus 35% 5-benzoate. 4 Plus 45% of an approximately 1:1:1 mixture of the three possible di-0-benzoyl derivatives. Also 18% of a mixture of 2.3- and 3,4-disubstituted products. Plus 23% of the 3.4-di-0-benzoyl derivative. ' As the lactone. J

'

-

84

0

259

4" 28

260

4" 18 4" 14 4 26 -

260 260

27

0

260 261

OBn

OH

HO HO

h:nOBn

55 R = B n 56 R = CH,CH,SiMe, 57 R = A l l

OAll \

OAc

54

HO

58 7

0

HO

&

OH

59 cAo*&:

OH

NH*

OBn

HO

OBn

O I

OAll

60

OAc

c q

61

HO

+

HO

&

OBn

0

AcO

4

62

OMe

63

OMe

HO

64

OH

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

89

66

OBn

H,C h

O

B

& p &

n

/OBn OpOMeBn NHAc

HO OH

67

hoBn

OBn

H3C

HO

,OBn

&hO OBn

OH

68

90

T. BRUCE GRINDLEY

HO NRR'

69 R = H , R'=Ac 70 R, R ' = Phth

HO OH

71 R = M e 72 R = B n 73 R = CH,CH,SiMe, 74 R =y-AllyloxyBn 75 R = 4-Pentenyl PI1

OpOMeBn

HO

NHAc

OH

76

OBn

OpOMeBii HO

77

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

h p $ $ /

91

0

.O

HO OH

78

HO OH

79

HO

80 R = O H 81 R = N H A c

HO H O3*c0Bn k o l I q

0

HO

% 83 HO OH&

OH

82

SPh

OH

OCH,CH,SiMe,

92

T. BRUCE GRINDLEY

NHCbz

Me0

HO HO OH

OH

85

84 7

OH

H

OH

H

OH

OH

88

4

HO

OH

&

OH

91

90

c

d

H , $OHH o M e

HO

OH OBn

OBn

OH

93

92

BnO

All0

RO

HO O

89

,

OH

87

86

RoH

OH

0

OBn

95 R = A l l 96 R = B n

OMe

OH

94

dOH &/ All0

OAl

p-MeOBnO

BnO

97

OBn

OBn

98

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

OH

Bn@oH

93

Bngn+&

BnO

BnO

BnF-

99

OBn BnO

OBn

BnO

RO

I

S

O

“ RO

100

?H

?H

I

RO

H AIIOAllO

OR

OAll

OH

AllO

’OR

OH

101 R = p-MeOBn

104 R = B n

103

102 R = B z

105 R = p-MeOBn OH

O B *n BnO

OH OAll

OH

OBn

106

OBn

107

108

OH

OH B BnO n

O

6OH

I

BnO

PrCOO PrCOO -0,

OBn

109 X = F 110

OBn

111

x=c1 OH

OBn

BnO

OH

I

AllO A AllO 1

’

o

S

O

OAll

112 OH

p”

I

OBn

OBii

114 Cr = -CH,CH=CHCH,

115

H

T. BRUCE GRINDLEY

94

OBEt,

OBEt, OBEt,

116

118

OH

117 Me

I

HO

OH

119

HO

121

120

HO

q,

C0,Me

OR

122 R = M e 123 R=All

HO

HO

SEt I

124

CO,El

125

OH

126 R = R = H 127 R - H R ' = M e 128 R = C N R'=Me 129 R = Me R' = Me

130

131

OAll

01

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

I

95

I

OH

HO

132

I H 136

The reactions performed on dibutylstannylene acetals formed from galactopyranose derivatives having only 0 - 3 and 0 - 4 unprotected are amazingly regioselective; as shown by numerous groups, treatment with every electrophile except bromine gives only substitution at the equatorial oxygen atom, 0-3. Bromine oxidizes this type of compound with high regioselectivity at 0-4. Figures 33 and 34 illustrate some of the wide range of conditions that give these two types of regioselectivity. Even when there are other unprotected hydroxyl groups in the substrate, 0-3 of dibutylstannylene acetals of the cis-diol of the gulucto configuration reacts with electrophiles with high regioselectivity. Figure 35 shows some of the most spectacular examples: those for P-lactosides, where the reactive oxygen atom is one of seven unprotected. The last example in Fig. 35, where the electrophile is t-butyldimethylsilyl chloride (e), illustrates a consistent pattern with this e l e c t r ~ p h i l e and ~ ~ -other ~ silylating agents88to yield the product of reaction with a primary oxygen atom, when available. One other reaction on a substrate with this configuration has yielded small amounts of primary product when the primary hydroxyl was free,'= but probably small amounts of second products are present in many cases when the yields reported are in the 50 to 80%range. Nevertheless, the regioselectivity obtained for these substrates is highly impressive and very useful synthetically. The regiochemistries of reactions on dibutylstannylene acetals of amannopyranosides having only the cis-1,Zdiol on 0 - 2 and 0-3 free are much more complicated than those just discussed. By far the greatest extent

T. BRUCE GRINDLEY

96

OBn

2b. AllBr, Bu,NI Toluene, 80 OC

55 R1 = Bn 56 R1 = CH,CH,SiMe,

2c. Bar-DMF, lO0OC

57 R1=All

a. R1 = Bn, R2 = S03NEt3 83% b. R' = CH,CH,SiMe,, R2 = All 91% c. R1 = All, R2= Bn 81%

FIG.33.-Reactions of the dibutylstannylene acetals of 2,3,6,2',6'-penta-O-benzyI-P-lactose glyc~sides.'~~~'~~~'~'

of substitution still occurs on the equatorial oxygen atom, 0-3, but, in contrast to the results for the galactose derivatives, significant amounts of substitution on the axial oxygen atom, 0-2, were often obtained. In fact, preferential substitution of this position was observed on reaction of the dibutylstannylene acetal of methyl 4,6-O-benzylidene-a-~mannopyranoside with benzoyl chloride in nonpolar solvents in the absence of added n u ~ l e o p h i l e s , ~and * ~ also ~ ~ ~with + ~ the ~ ~ triethylamine-sulfur trioxide complex in DMF (see Fig. 36).lo7However, in the presence of added

-

OH

1 . Bu,SnO

HO

OBn 2. Br.-CKCL Br2-C&C12

nBO- *HO ' OBn

OBn

60

76%

FIG. 34.-Oxidation of the dibutylstannylene acetal of benzyl 2-O-benzyI-P-~fucopyranoside with bromine.'62

97

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

1. Bu,SnO H HO "O&;

OH OR'

OH

71 R 1 = M e

2a. AlIBr, Bu,NBr-Benzene,

80 "C

2b. p-MeOBnCI, Bu,NI-Benzene,

80 OC

2c. MeI, Bu4NBr-CH3CN, 45 "C

72 Rl = Bn 75 Rl = 4-Pentenyl

2d. AlIBr, Bu,NBr-Benzene,

80 OC

2e. TBDMSCI- THF,RT

RzO

OR1

OH a. R1 = Me, R2 = All, R3 = H 70%

b. Rl = Me, R2 = p-MeOBn, R3 = H 70% c. R l = M e , R , = M e , R 3 = H

54%

d. R1 = Bn, RZ= All, R3 = H 61% e. RI = 4-Pentenyl, R2 = H, R3 = TBDMS 92% FIG.35.-Reactions of the dibutylstannylene acetals of p-lactose giyc~sides.'~~,'~.''~.'~.~~

nucleophiles, and under more vigorous conditions, as required for alkylation, the equatorial product becomes predominant. The X-ray crystal structure shows methyl 4,6-0-benzylidene-2,3-0dibutylstannylene-D-mannopyranosideto be a pentamer." In the pentamer, the two terminal monomer units have 0 - 2 dicoordinate. The

Ph

T*

1. Bu,SnO

AMe2. For reagents see below BzCI - Benzene BzCI, NMI - Benzene Et3N.S03- DMF

I

OMe

R' = Bz, R2 = H 85% R ] = H , R ~ = B 15% Z R' = H,R~= BZ 90% R1= Bz, R2 = H 0% R' = S03NEt,, R2= H 70% R' = H, R2= S03NEt3 14%

FIG.36.-Reactions of the dibutylstannylene acetal of methyl 4,6-O-benzylidene-a-~mannopyrano~ide.'~~'~~

98

T. BRUCE GRINDLEY

l19Sn NMR spectra of this compound indicate that it is less associated in solution, being present as a mixture of a symmetrical dimer and a trimer in chloroform-d and of the dimer, the trimer, and a tetramer in toluene-d8:' The populated dimer is probably the 3,3-dimer with 02 dicoordinate. Thus, these products could be the result of trapping of 'the more populated dimer in solution by reaction of reactive electrophiles with the more nucleophilic oxygen atom. Alternatively, the intermediate formed initially may rearrange during workup, as demonstrated for esterification of acyclic diols (see earlier).53 Alkylation reactions of dibutylstannylene acetals of compounds having this stereochemistry give variable degrees of regioselectivity for 0-3 in a rather unpredictable manner. However, none of the reactions on this type of substrate performed in DMF containing CsF gave anything other than complete regiospecificity for 0-3. Therefore, this method is the best choice to obtain this regiochemistry. Although not nearly as mainly results are available for other stereochemistries, regioselectivities seem to be in accord with those already noted. Thus, allopyranosides react at 0 - 2 when 0-4 is and talopyranosides have a reference for reaction at 0-3.9*205.233 Although not nearly as many reactions have been performed on tributylstannyl ethers of cis-diols, the effect of varying stereochemistry was examined in a systematic fashion for 1,6-anhydropyranoses by Martin-Lomas and his co-workers.68As shown in Fig. 37, the outcome is similar to that anticipated for similar reactions on dibutylstannylene acetals. Table VI also lists the numerous reactions that have been performed on dibutylstannylene acetals of inositol derivatives containing cis-diols, mostly in myo-inositol derivatives. Most reactions were alkylation reactions and, almost without exception, single products were obtained with the substituent on the equatorial oxygen atom. In most cases, yields were greater than 80%, and in only a few cases were yields lower than 70%. The fructopyranoside and arabinopyranoside reactions are listed in Table VI because the regiochemistry associated with the cis-diol is more important in controlling their regiochemistry of reaction than the lack of substitution of one side of the diol. Thus, the fructopyranoside derivatives react with electrophiles other than bromine at 0-4,8'J47the equatorial oxygen atom of the cis-diol, and with bromine at the axial oxygen, 0-5.81Although 0-3 is generally favored, the regioselectivity observed for arabinopyranosides is lower than for most of the other cisdiols, presumably because there are not great stability differences between the 'C, and 4C1conformations. Based on the foregoing observations, dibutylstannylene acetals of 8O-protected Kdo derivatives should display great selectivity for 0-4, an

99

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

DOH 1. Bu,SnOSnBu,

p

+

2. BnBr, NMI -toluene, 120 o c

I

OH

OH

86

7

OBn

25%

65%

0 1. Bu,SnOSnBu,

* 2. BnBr, NMI -toluene,

I

87

BnO

120 o c

OH

OH

93%

FIG. 37.-Regioselectivity obtained in benzylation of tributylstannyl ethers of two anhydropyranoses."R

equatorial oxygen oxygen atom that has a deoxy center at C-3 and a cis oxygen atom at C-5. This regioselectivity was obtained, but the reactions of a-glycosides are complicated by concomitant lactone formation, as shown Only when the large TIPS group is used to protect 0-7 and in Fig. 38.252.253 0-8 is lactone formation inhibited.262 The furanose derivatives listed in Table VI present an interesting contrast. The acylation reactions are fairly selective,' usually for 0-3', whereas the alkylation reactions are relatively n o n ~ e l e c t i v e . Presumably, ' ~ ~ ~ ~ ~ ~ ~the ~ regi-

1 . Bu,SnO / Benzene

HO

BnO

C0,Me

122

OMe

2. BnBr, Bu,NBr, NaI 80 O C 19h

72%

FIG.38.-Benzylation of a dibutylstannylene acetal of a cis-diol on a molecule that also contains a methyl ester, which results in concomitant lactone formatio11.2~~

OH

100

T. BRUCE GRINDLEY

oselectivity on acylation is the result of eq~ilibration?~ whereas the lack of regioselectivity in alkylation reactions indicates the lack of kinetic preference for 0 - 2 or 0-3. Nevertheless, the preferences of dibutylstannylene acetals to give monosubstitution, and reaction at a secondary site of a cisdiol over an unprotected primary oxygen atom, can be synthetically Figure 39 shows a spectacular example of the selectivity of reactions of dibutylstannylene acetals of vicinal cis-diols over isolated diols, for 2'-0acetyltylosin, where one secondary hydroxyl of the three available reacts because it is the only one vicinal to another hydroxyl group. In the sequence shown, reflux in methanol removes the 2'-O-acetyl group?60 Table VII lists the comparatively few di- or poly-substitution reactions that have been performed on dibutylstannylene acetals and tributylstannyl ethers of compounds containing cis-diols. Figure 40 (page 103) shows some of the

1. Bu,SnO

- toluene

2. p-Methoxyphenylacetyl chloride 3 . Methanol, reflux

11,111

OR

2 8% OMe FIG.39.-Synthesis of 4"-O-p-methoxyphenylacetyltylosin?m

TABLE VII Formation of Di-0-substituted Derivatives from cis-Diols

Compound Methyl 0-D-galactopyranoside

Reaction Conditions Acetal or Ether Solvent Nuc" Temp. ("C) Ether Ether Ether Acetal Ether Ether Ether Acetal

2-(Trimethylsilyl)ethyl 2,3,6-tri-O-benzyI-40(P-D-galactopyranosyl)-fl-D-glucopyranoside (136) 2-hidoethyl P-D-galactopyranoside Acetal Methyl a-D-galactopyranoside Ether

3,6-Di-O-benzyl-4-0-(2-0-benzyl-/3-~galactopyranosy1)-D-glucal

Acetal Acetal and ether

Toluene Toluene DMF BnBr BnBr AllBr Toluene Toluene

20 Amb. 25 85 85 80 60

4 Amb. 20

Pyridine Toluene

85

BnBr Benzene TBAB

80

Yield (%) Electrophile

23

0 Benzoyl chloride Pivaloyl chloride 0 ET3N . SO3 0 Benzyl bromide 38 Benzyl bromide 6 24 Ally1 bromide 6 11 Trityl chloride 2,6 72 Benzoyl chloride 0

Pyridine . SO3 Benzoyl chloride Benzyl bromide Benzyl bromide

0 6 22 2.6 10 0

2,4

3,4

Ref.

0 0 0 0 0 0 0

3.6 95 3,6 86 3,6 76 3,6 70 3,6 48 3,6 51 0

74 264 107 151 263 263 263

0 3',6' 89 120 0 3,6 71 115 3,6 21 2 3 74 40 0 3,6 63 151 3',6' 90 182 (continues)

TABLE VII (ConTinued)

Compound

Reaction Conditions Acetai or Ether Solvent Nuc’ Temp. (“C)

Methyl 6-chloro-6-deoxy-cr-~-mannopyranosideAcetal Methyl a-D-maMopyranoside Ether Ethyl 1-thio-a-D-mannopyranoside Acetal 1,6-Anhydro-/3-~-talopyranose (91) Ether l&O-isopropyhdene-/3-D-fructopyranose (119) Acetal Ether Methyl @-D-arabinopyranoside Ether Acetal (-)-chiro-Inositol (W7) Ether

Hexa-0-diethylboronyl-myo-inositol(116) Lactose

Etherb Ether

Benzene Toluene DMF CsF Toluene NMI Benzene Benzene Benzene Benzene CH3CN TBAI Toluene NMI Toluene

Added nucleophile; for abbreviations of nucleophile names, see Table IV Three equivalents.

80 20 Amb.

120 80 Amb. 50

80 82 Amb.

45

Yield (%) Eleetrophile

2,3

Benzoyl chloride 90 Benzoylchloride 0 Benzyl bromide 0 Benzyl bromide 0 Benzoylchloride Benzoylchloride Benzoyl chloride 0 Benzoyl chloride 17 Benzyl chloride 2,3,5

2,4

3,4

Ref.

0

0 0 0

18 74 218

3,6 90 3,659 95 50 0

2,3,5,6 32 6 Benzyl bromide 1,3 48 1,5 20 Benzoyl chloride 2,6,3’,6’ 72

0

4,5100 4 3 95 50

80

6

8

18 18 18 18 265 246 74

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

1. Bu,,SnO-toluene

HO

BnO

2. BnBr, 80 "C, 26 h

OH

HO

*

OMe

&

&

OMe

OH

R=Bn OH

1. (Bu3Sn),0

OMe

OH

103

R'O

70%

OR2

!&& 0

OMe ~

3

2a. BzCI- toluene

R1= R2= Bz R3 = H 95%

2b. E$N.SO,-DMF

R' = R2 = S03NEt, R3= H 76%

2c. BnBr, 80°C, 26 h 2d. TrCI-toluene, 60 oC, 35 h

Rl=RZ=Bn R3=H 48% Rl=R3=Tr R2=H 72%

FIG. 40.-Major products obtained in the di-0-substitution of methyl galactopyranoside.'4~'"7~"3~2h'

p-D-

reactions performed on methyl P-D-galactopyranoside.Both tributylstannyl ethers and dibutylstannylene acetals yield 3,6-di-O-substituted derivatives as the major products in most cases,74J07-151,263 although tritylation of the tributylstannyl ether afforded the 2,6-di-tritylether as the only di-0-substituted When no primary hydroxyl is available, di-0-benzoylation of either the dibutylstannylene acetal or the tributylstannyl ether was observed to occur at the site of the cis-diol, as observed for methyl 6-chlorod-deoxya-D-mannopyranoside or 1,2-O-isopropylidene-P-~-fructopyranoside.~~ However, di-0-benzylation for 1,6-anhydro-P-~-talopyranose (91),which has two equatorial hydroxyl groups adjacent to an axial hydroxyl, occurs in good yield on the equatorial oxygen atoms.68When primary hydroxyl groups are available, the major di-0-substituted product almost always has substitution at the primary oxygen atom.74~'07~'15~120~218

4. Diols Adjacent to Deoxy Centers or Double Bonds Numerous examples as listed in Table VIII demonstrate that lack of substitution adjacent to a 1,2-diol causes reactions of its dibutylstannylene acetal to occur on that sterically less hindered oxygen atom. Some examples that illustrate the trends are shown in Figs. 41 to 44 (page 107). The

TABLE VIII Reactions of Dibutylstannylene Acetals and Tributyltin Ethers of Diols Having Adjacent Deoxy Centers or Double Bonds

Yield (YO)

Reaction Conditions Compound

Acetal or Ether

1,5-Anhydro-l-amino-4,6-0- Acetal benzylidene-Nbenzyloxycarbonyl-1-deoxyD-glucitol (l39) Acetal Acetal Methyl 2,6-dideoxy-a-~arabino-hexopyranoside (140) Methyl 2.6-dideoxy-3-Cmethyl-a-D-arabinohexopyranoside (141) Butyl 2,6-dideoxy-P-~~arabino-hexopyranoside (142)

Methyl 2,6-dideoxy-a-~arabino-hexopyranoside (143)

p-Methoxybenzyl 2,6-dideoxydpL-arabinohexopyranoside (144) Methyl 2,6-dideoxy-a-~-lyxohexopyranoside (145) Methyl 2,6-dideoxy-P-~-lyxohexopyranoside (146)

Solvent

Nuc'

Temp. ("C)

Electrophie

0-3

0-4

Ref.

73

0

-

268

94

0-2

Benzene

Amb.

Benzoyl chloride

Benzene

Amb. 110

Tosyl chloride Benzyl bromide

0 85

-

-

0

268 273

DMF

Acetal

Toluene

Et3N

Amb.

Benzoyl chloride

-

80

12

267

Acetal

Toluene

TBAI

110

Benzyl bromide

-

86

0

266

Acetal Acetal

Toluene Benzene

TBAI Et3N

26 -45

Tosyl chloride Benzoyl chloride

-

98 70'

0 0

266 269

Acetal Acetal Acetal Acetal

Benzene Benzene Benzene Toluene

TAB1 TBAI Et3N

Amb. 80 80 -40

Tosyl chloride Benzyl bromide Methyl iodide p-Nitrobenzoyl chloride

-

7s 70 72 72

0 0 18 0

269 269 269 274

Acetal

Toluene

TBAB

80

t-Butyldimethylsilyl chloride

-

85

0

178

Acetal Acetal

Benzene Benzene

TBAI

80 Amb.

Benzyl bromide Tosyl chloride

-

84 90

0 0

275 269

Acetal

Benzene

TBAI

80

Benzyl bromide

-

9s

0

79

-

Methyl 2,6-dideoxy-c~-~-lyxohexopyranoside (147)

Toys1 chloride

-

98

0

269

Benzyl bromide Benzyl bromide Benzyl bromide

-

48

-

95 60

0 0 40

270 269 271

Acetal

Benzene

Acetal Acetal Acetal

Benzene Benzene Benzene

Ether

Toluene

Amb.

Benzoyl chloride

Acetal

Toluene

111

Acetal

DMF

45

Acetal Acetal Acetal

DMF DMF CHzC12

CsF CsF CsF

Amb. Amb. -45

Castanospermine (53)

Acetal Acetal Acetal Acetal Acetal Ether

MeOH MeOH MeOH Toluene Toluene Toluene

Et3N Et3N Et,N

Amb. Amb. Amb. - 10 Amb. -10

Methyl cY-D-xylopyranoside

Ether Acetal Acetal Acetal Acetal Acetal Acetal Acetal

CHCI, 1,4-Dioxane lP-Dioxane DMAP 1,4-Dioxane 1,4-Dioxane 1,4-Dioxane 1,4-Dioxane Benzene TBAB

0 Amb. Amb. 100 100

Acetal Acetal Ether

Ip-Dioxane Benzene Toluene

Amb. Arnb. 0

Methyl 2,6-dideoxy-c~-~-ribohexopyranoside (148) Methyl 4,6-dideoxy-P-~-xylohexopyranoside (149) Methyl 2-deoxyl-P-~-eryrhropentopyranoside (150) Methyl 1,5-di-O-acetyl-(-)quinate (151) 152 153 154

Methyl 2-azido-2-deoxy-a-~xylopyranoside Methyl P-D-xylopyranoside

Amb. TBAl TBAI TBAl

80

80 80

50 100 80

-

94

0

Benzyl bromide

-

47

43

277

Trityl chloride

-

65

0

272

1' 99 2 ' 0 1' 63 2' 18 1 20 >66 6 40 0 0 6 39 0 0 0 0 644 0 0 6 94 6 76 0 0 0 0 1,6 75 0 0 92 52 0 30 52 32 0 6 3 4 57 6 23 47 28 50 12 0 28 37 70 13

278 278 279

p-Methoxybenzyl chloride p-Methoxybenzyl chloride 2-(Trimethylsilyl)ethoxymethyl chloride Acetyl chloride Decanoyl chloride Benzoyl chloride Benzoyl chloride Benzyl chloroformate Pivaloyl chloride (2 equiv) Bromine Benzoyl chloride Tosyl chloride Benzyl bromide Ally1 bromide Methoxymethyl chloride Methyl iodide Benzyl bromide Benzoyl chloride Benzoyl chloride Benzoyl chloride

0 0 0

0 0 0

276

-

loo 93 100

280 280 280 281 281 282 77 130 106 131 131 131 131 283 130 132 130

(continues)

TABLE VIII (Continued)

Yield (YO)

Reaction Conditions Compound

Ally P-D-xylopyranoside Benzyl P-D-xylopyranoside 2-Naphthyl &Dxylopyranoside 6-O-Trityl-~-gl~~al 6-O-t-Butyldimethyls~yl-Dglucal 6-Deoxy-~-glucal L-Rhamnal (155) D - F u (156) ~ D-Arabinal (157) D-Glucal

158 Methyl 5-O-acetyl-(-)shikamate (159)

A c e d or Ether

Solvent

Nuc." Temp. ("C)

Electrophile

Ether Acetal Acetal Acetal Acetal Acetal Acetal Acetal

CH2C12 1,4-Dioxane 1,4-Dioxane DMAP 1,4-Dioxane 1,4-Dioxane Benzene Benzene Benzene

Amb. Amb. Amb. 100 50 Amb. Amb. Amb.

Chloroacetyl chloride Phenoxythiocarbonyl chloride Tosyl chloride Benzyl bromide' Methoxymethyl chloride Benzoyl chloride Chloroacetyl chloride Chloroacetyl chloride

Acetal Acetal

CH2C12 Toluene

Et,N TBAB

Amb. 80

Benzoyl chloride Benzyl bromide

Acetal Acetal Acetal Acetal Acetal Acetal Ether Ether

Toluene DMF CH2C12 THF DMF Toluene Benzene Benzene

TBAB CsF EtSN CsF CsF TBAB

0 Amb. Amb. Amb. 80 70 Amb. Amb.

Methoxymethyl chloride Benzyl bromide Benzoyl chloride Methyl iodide p-Methoxybenzyl bromide Tosyl chloride NIS Benzyl bromide

Acetal Acetal Acetal

DMF DMF DMF

CsF CsF

Amb. Amb. Amb.

t-Butyldimethylsilyl chloride Benzyl bromide Dimethoxytrityl chloride

TBAB

Added nucleophile; for abbreviations of nucleophile names, see Table IV. Also 9% of the di-0-benzoyl derivative. With 24 equiv: 6 equiv gave an 0-2, 0-3. 0-4 mixture of yields of 35 to trace to 356, respectively. Plus 10% 3.4-di-0-methoxymethyl derivative. 'Ketone product. With NIS in acetonitrile or with bromine or iodine in any solvent, 2-halo-1.6-anhvdro

derivativec are

0-3

0-4

Ref.

0 0 0 0 41 0 0 0

0 0 0 0 6 0 0 0

78 97 100 70 34 82 81 72

117 70 106 131 131 132 284 285

-

88

0

-

93

0

286 287

0-2

3,6 73 -

nhtPin-ri

70d 66 78 73

73 0 60' 0

28 38 68

288 219 286 289 0 210 60 290 0 291 0 182, 292 0 0 0 0

0 0 0

293 293 272

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

107

pllT:&

-

N-COOBn

HO

HO OH

OTs

2. TsCI,E&N

139

94%

FIG.41 .-p-Toluenesulfonation of the dibutylstannylene acetal of 4,6-O-benzylidene-Nbenzyloxycarbonyl-l-deoxy-norjirimycin.270 1. Bu,SnO

-

toluene

B

z

o

H

CH,

141

+

w OMe

CH3

12%

FIG.42.-Benzoylation

80%

of a secondary-tertiary dial?'

1. Bu,SnObenzene

H,C

2. BnBr,TBAI,

OH

80 "C

OH

95%

147 FIG.43.-Benzylation of a the dibutylstannylene acetal of a pyranose cis-diol having the equatorial oxygen atom next to a deoxy 1 Bu,SnO

benzene

B

n

2 BnBr,TBAI, 80 oc

o

M

OH

148

OMe

+

HoM OBn

40%

60%

1. Bu,SnO

C0,Me

2. TrCl / DMF

OAc

OTr OAc 65%

FIG.44.-Alkylation of dibutylstannylene acetals of a pyranose cis-diols having axial oxygen atoms next to a deoxy enter?^'.^^'

T. BRUCE GRINDLEY

108

dibutylstannylene acetal of compound 142, where the oxygen atoms are both equatorial, reacts only on the atom adjacent to the deoxy Even when the oxygen atom next to the deoxy center is tertiary, as in Fig. 42, reaction occurs mainly at this point.267When the equatorial oxygen atom of a cis-diol is next to the deoxy center, as in Fig. 43, only one product is formed. However, when the axial oxygen atom is next to the deoxy center, the two factors determining regioselectivity are in conflict and mixtures result, as shown in Fig. 44.

/ OBn

OH I

2

p h Y & J -.-

AH 138

HO

5

OH

139

How HO H

HO

H HO

O

W

OMe

CH,

OMe

140

W

I

,

e

,

142

I HO H

o

HO

141

OMe

HO H

CBZ

0

HO=OH HO'

?H

W

Ho&

W HO

OH

143

144

145

OMe

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

109

H3c-p0 H3cw0Me 146

OH

H

O

W

147

OH

O

M

e

148

C0,Me

OH OMe

149

OH

150

OAc

151

OH OH

155

154 R

= 3,4-dimethoxybenzyl

OH

156

OH

OH

157

159

T. BRUCE GRINDLEY

110

I . Bu2SnO-l ,4-dioxane

*

OMe

p,,ocso H

a OMe

2. PhOCSCl

OH

OH 97%

1. Bu2SnO-1,4-dioxane b B HO 2 -

q

+; H

,

2. PhCOCl

BzO

OMe

Ok

OMe 5 2%

3 0%

FIG.45.-Esterification of dibutylstannylene acetals of p- and a-~-xy~opyranosides.~"~~~"

Oxygen atoms at position 4 of dibutylstannylene acetals of pentopyranosides are also quite reactive, presumably because the lack of obstruction to the approach of electrophiles increases the rate constant for reaction at that position. Thus, dibutylstannylene acetals of P-xylopyranosides usually react exclusively at 0 - 4 (see Fig. 45), whereas a-xylopyranosides give mixtures of products at 0 - 2 and at 0 - 4 (see Fig. 46). Oxygen atoms in diols adjacent to double bonds exhibit a similar effect. Their dibutylstannylene acetals react preferentially on the allylic oxygen atom, as shown in Fig. 46. 5. Terminal

14-and 1,3-Diols

The reactions of tributylstannyl ethers and dibutylstannylene acetals of diols or polyols containing one hydroxyl group that is at the end of a chain (terminal diols) are listed in Table IX. Some reactions on compounds of this type, primarily unprotected glycosides, have been discussed earlier, but for those examples, the terminal hydroxyl group was not critical in

1 . Bu2SnO- toluene

HO

H

O

A

R,O

R = OTr

2. BzCI, Et,N-

CH2C12

R = OTBDMS 2. BnBr, TBAB - toluene, 80 "C R=H 2. BnBr, CsF - DMF, RT

R,=Bz

88%

R, = Bn 93%

R, = Bn 66%

FIG.46.-Reactions of dibutylstannylene acetals of glucal derivative^?'^.^,^^^

TABLE IX Reactions of Dibutylstannylene Acetals and Trihutyltin Ethers of Terminal 12- or l,3-Diols ~

~~

~~

Yield (%) Reaction Conditions Compound I,2 Diols 1,2-Propanediol

1-Phenyl-l,2-ethanediol

1,2-Hexanediol 12.4-Butanetriol

1,2,6-Hexanetriol 1-0-Methylglycerol 1-0-(p-Methoxyphenyl) glycerol

Acetal or Ether

Solvent

Nuc.” Temp. (“C)

Acetal Acetal

CHCI3 CHCI3

Acetal Acetal Acetal

DMF CHC1, CHC13

CsF

Acetal Acetal Acetal Acetal Acetal Acetal Acetal Acetal Acetal Acetal

DMF CHC13 Benzene Benzene DMF CHCI3 Benzene Benzene DMF CHC13

CsF

Ether Acetal Acetal Acetal

Toluene CHC13 DMF DMF

Amb. Amb.

Et3N Et3M CsF Et3N EQN CsF

Amb. Amb. Amb. Amb. Amb. 0 0 Amb. Amb. 0 0 Amb. Amb.

0 CsF CsF

Amb. Amb. Amb.

Electrophile

Benzoyl chlorideb 1-Butyldimethylsilyl chloride Benzyl iodide Benzoyl chlorideh r-Butyldimethylsilyl chloride Benzyl bromide Benzoyl chloride” Acetyl chloride Tosyl chloride Benzyl bromide Benzoyl chloride‘ Acetyl chloride Tosyl chloride Benzyl bromide t-Butyldimethylsilyl chloride Benzoyl chloride Benzoyl chlorided Benzyl iodide 1-Bromohexadecane

Secondary Site

Terminal Site

Ref.

71 0

13 74

84 87

9 86

91

69

5

84

0

97

87

10

0 - 2 86 7 70 82

69

55

0 0 0 60 0 0 0 0

0 55

10 8

80 24 0 - 1 71 0-1 72 0-1 70 0-4 99

0-1 67 17 67 90

84

12 12 12 84 12 12 12 87 14 84

69 294

(continues)

TABLE IX (Continued) Yield (YO) Reaction Conditions Compound 1-0-Benzylglycerol

3 +

N

Methyl 2,3dihydroxypropanoate 12-O-Isopropylidene-Lthreitol (160) 2-O-Benzyl-l-O-rbutyldiphenylsilyl-L-threitol (161) 3,4-Di-O-benzyl-~-mannito1

12:3,4-Di-O-isopropylidene-

Acetal or Ether

Solvent

Nuc'

Temp. ("C)

Acetal Acetal Acetal Acetal Acetal

CH2ClZ-THF 4 : 1 DMF DMF DMF DMF CsF

Acetal

Toluene

Acetal

CHIC12

Acetal

Toluene

Acetal

CHC13

Acetalc Acetal

CHC13 CHC13

Acetalc Acetal

CHCL Dioxane

Acetal

Toluene

TBAI

20

Acetal Acetal

Toluene Toluene

TBAB TBAB

70 111

TBAI

TBAI

0 90 100

90 Amb.

Electrophile Acetyl chloride 1-Bromododecane 1-Bromohexadecane I-Bromooctadecane Benzyl iodide

Secondary Site

Terminal Site

Ref.

0 0 0 0 14

65 71 71 62

294 295 296 295 69

84

70

Benzyl bromide

0

84

297

40

Tosyl chloride

0

85

298

70

0

20

Benzyl bromide (4 equiv) Tosyl chloride

20 20

Tosyl chloride Tosyl chloride

1,6 74

299

2

96

20

58 12

38 80

20 20

60 1,6 46

17 1.5 20

20 300

1,6 67

Cyclized 15 301

1,6 60 1,6 54

302 300

D-mannitol 3,4-Di-O-benzylll,2-0-

isopropylidene-D-mannitol (2S,5S)-12,5,6-Hexanetetraol

20 Amb.

(162)

Tosyl chloride Benzoyl chloride (2.2 equiv) Tosyl chloride (2.1 equiv) Benzyl bromide Benzyl bromide (4 equiv)

(2S,3E,5S)-Hex-3-ene-l,2,5,6tetraol (163) (2S,4Z,6S )-7-)tButyldimethy1silyloxy)-hept4-ene-1,2,6-triol (164)

Acetal

Toluene

Acetal

MeOH

(2R,3S,4E)-3-Methyl-S-phenyl-Acetal 4-pentene-1,2-diol (165) 1,2-O-Isopropylidene-3-0Acetal methyl-a-D-glucofuranose

3-0-Benzyl-1,2-0isopropyhdene-a-Dglucofuranose c W

3-O-Benzoyl-1.2-0isopropyhdene-a-Dglucofuranose

1,2-O-Isopropylidene-3-O-ptoluenesulfonyl-a-Dglucofuranose 3-O-Benzyl-l,2-0isopropylidene-a-Dglucofuranose 3-Deoxy-3-fluoro-1,2-0isopropylidene-a-Dglucofuranose 3-Deoxy-3-iodo-l.2-0isopropylidene-a-Dallofuranose

Toluene

EtjN

O + 25

Tosyl chloride (2.1 equiv) Tosyl chloride

1,6 83

Tosyl chloride

0

20

301

303

1 68

82

14

0

76

Benzene

Amb.

Bromine

48

Acetal Acetal Acetalf Acetal

CHC13 Benzene CHC13 Toluene

Arnb. Amb. 20 20

NBS Benzoyl chloride Tosyl chloride Tosyl chloride

95 7.5 89 20

0 38' 5 78

82 76 20 20

Acetal Acetalf Ether

CHC13 CHC13 Benzene

20 20 Amb.

Tosyl chloride Tosyl chloride Bromine

39 95 65

59 4 0

20 20 304

Ether

Benzene

Amb.

Bromine

70

0

304

Acetal

CHC13

Amb.

NBS

90

0

82

Acetal

MeOH

0

75

305

Ether

Benzene

57

0

304

Et3N

0

Amb.

Benzoyl chloride

Bromine

(continues)

TABLE IX (Continued) ~

Yield (YO) Reaction Conditions Compound

Acetal or Ether

Solvent

Nuc" Temp. ("C)

Electrophile

Secondary Site

Tenninal Site

Ref.

3-O-Benzoyl-1,2-0isopropylidene-a-~allofuranose

Acetal

Pyridine

20

Benzoyl chloride

0

>65

80

1,2-O-Isopropylidene-3-0-

Acetal

CHC13

20

Tosyl chloride

0

98

20

Acetal

DMF

CsF

Amb.

8

85

306

3-Deoxy-l,2-O-isopropylidene- Acetal

DMF

CsF

Amb.

Benzyl bromide, TBAI Benzyl bromide

0

66

307

Amb.

Bromine

92

0

304

Tosyl chloride Tosyl chloride Bromine

5 51 5 92

94

0

20 20 77

Bromine NBS Benzoyl chloride Tosyl chloride Tosyl chloride

5 50

50

0 0 75 98 90

308 82 106 106 20

me thyl-a-o-allofuranose

3-C-methyl-a-~allofuranose (166) 1,2-0-Isopropylidene-3-deoxy- Ether a-D-ribo-hexofuranose (167) Acetal Acetalf 1,2-O-Isopropylidene-a-~Ether glucofuranose Acetal Acetal Acetal Acetal 1,2-O-Isopropylidene-a-~Acetal allofuranose Methyl 2.3-0-isopropylideneAcetal a-D-mannofuranose Acetalf

Benzene CHC13 CHCl3 CHC13 CHZCIz CHCl3 Dioxane Dioxane CHCl3

20 20 0

0 Amb. Arnb. Amb. 20

584 50 50

48

CHC13

20

Tosyl chloride

0

98

20

CHCl3

20

Tosyl chloride

69

28

20

+ L

Ethyl 2,3-di-O-benzyl-P-~galactofuranose (168) [2R(S),3S,5R(S)]-2-(1Benzyloxy-2-propyl)-5-(2,2dideuterio-l.2dihydroxyethyl) 3-methyltetrahydrofuran (169) Methyl (methyl 3-deoxy-4,50-isopropyfidene-a-Dmanno-2octu1opyranoside)onate (170) Methyl (methyl 4-0-benzoyl5-O-benzyl-3-deoxy-a-~manno-2octu1opyranosid)onate (17l)

1,3-Diols 1.3-Butanediol

Acetal

MeOH

Et3N

Acetal

MeOH

Et3N

Acetal

Benzene

TBAB

80

Acetal

Benzene

TBAB

100

Acetal Acetal

CHC13 CHCl3

(2S,3S,4R)-2,4-Dimethylhex-5-Acetal

0 Amb.

Amb. Amb.

Benzene

Etfi

Benzene Benzene CHzCl

EtjN TBAI

Benzene Toluene

Amb.

Tosyl chloride

0

81

309

Tosyl chloride

0

81

310

Benzyl bromide

0

8 81

252

Methyl iodide

0

873

311

63 0

17 99

87

0

77

12

88 98 0

12 12 78

Benzoyl chlorideb r-Butyldimethylsilyl chloride Benzoyl chloride

84

ene-1,3-diol (172) Acetal Acetal Ether

Methy 2,3-O-isopropylidene-aD-mannopyranoside Ethyl 2,3-dideoxy-a-~-eryfhro-Acetal hexopyranoside (173) 1,3-O-Ethylidene-~-erythritol Acetal (174)

0

0 0 0 - 4 768

0

Tosyl chloride Benzyl bromide Bromine

TBAB

80

Benzyl bromide

0

82

312

TBAI

70

Benzyl bromide

0

55

313

50

(continues)

TABLE IX (Continued) ~~~~

Yield (YO) Reaction Conditions

Compound

+

c)

QI

Benzyl 2-Acetamido-3-0benzyl-2-deoxy-a-~glucopyranoside t-Butyldimethylsily 2-azido-2deoxy-B-D-glucopyranoside Benzyl 2-acetamido-3-0benzyl-2-deoxy-P-~glucopyranoside Ally1 3-0-benzyl-2-deoxy-2phthalimido-P-Dglucopyranoside 2,2,2-Trichloroethyl 2-deoxy-2phthalimido-Paglucopyranoside f-Butyldimethylsilyl 2-azido-3O-benzyl-2-deoxy-P-~glucopyranoside Methyl-3-azido-3-deoxy-2-0methyl-P-Dglucopyranoside (175) Benzyl 2,3-di-O-benzyI-a-oglucopyranoside Tigogeninyl 2,3-di-O-benzyl-PD-galactopyranoside

A c e d or Ether

Solvent

Nuc" Temp. ("C)

Electrophile

Secondary Site

Terminal Site

Ref.

Ether

Toluene

TBAB

80

Benzyl bromide

All 0

86

314

Ether

Toluene

TBAI

95

Benzyl bromide

All 0

70

315

Ether

Toluene

TBAI

111

Benzyl bromide

All 0

78

316

Ether

BnBr

90

Benzyl bromide

All 0

76

317

Ether

BnBr

80

Benzyl bromide

AU 0

60

156

Acetal

Benzene

TBAI

50

Benzyl bromide

0

77

12

Acetal

CHiCN

TBAB

80

Benzyl bromide

0

81

318

Acetal

Benzene

Amb.

Benzoyl chloride

0

90

76

Acetal Acetal

Benzene Toluene

80 111

Benzyl bromide Benzyl bromide

0 0

80 91

63 319

TBAI NMI

Benzyl 3-O-benzyl-a-~galactopyranoside Benzyl 3-O-allyl-a-ogalactopyranoside Ally1 2-acetamido-3-0-benzyl2-deoxy-a-~galactopyranoside Ethyl 2,3-O-isopropylidene-lt hio-a-o-mannopyranoside Methyl 2,3,6,2’,3’-penta-Obenzyl-B-D-lactoside (176) a-Cyclodextrin

Acetal

Benzene

TBAI

80

Benzyl bromide

0

72

63

Acetal

Benzene

TBAI

80

Ally1 bromide

0

60

63

Acetal

Toluene

TBAI

70

Benzyl bromide

0

73

320

Acetal

DMF

CsF

Amb.

Benzyl bromide

0

75

218

Ether

CH,CN

NMI

45

Methyl iodide

0

Ether Ether

Toluene Toluene

50 50

Methyl B-D-glucopyranoside

Acetal Ether Acetal

1,CDioxane Toluene 1,4-Dioxane

Acetal Acetal Acetal

1,4-Dioxane 1,4-Dioxane Toluene

Acetal

Toluene

Acetal Acetal Acetal

DMF DMF DMF

Et3N

Amb. Amb. Amb.

Acetal

DMF

Et,N

Amb.

Acetal

Toluene

Tosyl chloride 2-NaphthalenesuLfonyI chloride Benzoyl chloride Benzoyl chloride Phenoxythiocarbonyl chloride Tosyl chloride Tosyl chloride f-Butyldimethylsilyl chloride Trimethylsilyl chloride Decanoic anhydride Decanoyl chloride Octadecanoyl anhydride Octadecanoyl chloride t-Butyldimethylsilyl chloride

Methyl a-D-glucopyranoside

Sucrose (48)

Methyl a-D-mannopyranoside

Amb. 0 Amb.

DMAP

Amb. Amb. 100 100

100

6’ 78

119

Penta 6 9 Hexa 6 32 Hexa 6 78

321 321

All 0 All 0 All0

86 19 85

130 130

All 0 All 0 AUO

92 92 90

70 70 88

All0

93

88

70

0 0 0

6 Mh 6 6Sh 6 Mh

322 322 322

0

6 47h

322

All 0

84

88

(continues)

TABLE IX (Continued) Yield (YO) Reaction Conditions Compound

A c e d or Ether

Secondary Solvent

Nuc" Temp. ("C)

Methyl a-D-galactopyranoside

Acetal

Toluene

100

Ethyl 1-thio-P-D-lactoside (79)

Ether Acetal

Toluene THF

0 Amb.

Phenyl 2,3-dideoxyl-l-thio-aAcetal ~-threo-hex-2enopyranoside (177) Ethyl 2,3-dideoxy-a-~-eryrhro- Acetal hex-2-enopyranoside (178) D-GIu~ Acetal Uridine (l26)

Acetal

Cytidine (130)

Acetal

Adenosine (131)

Acetal

CHCl3

TBAB

Amb.

Benzene

TBAB

80

Toluene DMF-1,C Dioxane' DMF-1,4DioxaneJ DMF-1,4Dioxanej

100 Amb. Amb. Amb.

Electrophile r-Butyldimethylsilyl chloride Benzoyl chloride r-Butyldimethylsilyl chloride Tosyl chloride

Benzyl bromide r-Butyldimethylsilyl chloride t-Butyldimethylsilyl chloride f-Butyldimethylsilyl chloride t-Butyldimethylsilyl chloride

Added nucleophile; for abbreviations of nucleophile names, see Table IV. Followed by reaction with chlorodimethylphenylsilane. Followed by reaction with oxalic acid. Followed by reaction with chlorotrimethylsilane. ' Plus 24% 5,6-di-O-benzoyl derivative. 'Hexamethylenestannylene acetal. Plus 20% of the dimeric ester. Longer reaction times gave slightly increased yields plus small (2-5%) amounts of the 3-0-substituted derivatives. ' Plus 32% of a mixture of the 2,6- and 3.6-di-0-benzoyl derivatives. Solvent ratio DMF to 1.4-dioxane. 1 to 4. a

Terminal Site

Ref.

92

88

59'

130 86

0

86

210

0

86

323

All 0

67

88

Site

All 0 All 0 All 0

6' 96

All 0

5 91

85

All 0

5 82

85

All 0

5 80

85

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

119

determining the regiochemistry of the reaction considered. The complicated factors that influence regiochemistry in reactions of these organotin intermediates are understood best for the derivatives of these terminal diols, as outlined in Section VI. From a synthetic point of view, the most important observation is that dibutylstannylene acetals and tributylstannyl ethers can be used to effect terminal substitution of diols in excellent yields, often better than can be obtained by direct reaction at low temperatures, even for benzoylation or p-toluenesulfonylation, where direct reaction is reasonably effective. Terminal 0-alkylation, which cannot be performed directly, is routine through choice of the appropriate conditions, as outlined in the sections following. These types of reactions are considered first, followed by reactions where the nonterminal oxygen atom is favored.

OBn

OH

162 160

161

163

164 H O l

166

Ho "7c 167

OMt?

170

T. BRUCE GRINDLEY

120

Bn&

BzO

H

C0,Me

171 OMe

O

173

172

W OMe

174 OH

OH

boMe N3

BnO h

175

o

OBn &

Brio &

OBii OM

176

Hoe -

I

177

SPh

178

OEt

Both tributylstannyl ethers and dibutylstannylene acetals of terminal triols yield in most cases the product of reaction with 1,2-diolsin preference to other hydroxyl groups, as shown in Figs. 47 and 48. Figure 47 also illustrates the tendency of t-butylchlorodimethylsilane to react with terminal 1,3-diols in preference to terminal 1,2-diols.” Figure 48 shows that the preference for reaction at terminal oxygen atoms ,is considerably stronger than the preference for reaction next to unsubstituted centers, discussed in the previous section. As the numerous examples in Table IX demonstrate, this selectivity is maintained over a wide range of structural features. The two sets of conditions most employed for benzylation of dibutylstannylene acetals are benzyl bromide with cesium fluoride in DMF at room temperature and benzyl bromide with tetrabutylammonium iodide or bromide in toluene or benzene at elevated temperatures. Although there are no examples with careful analysis of the product mixtures where the same substrate has been allowed to react under both sets of conditions with terminal 12-diols, examination of Table IX suggests that the latter condi-

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

121

OH H

0

L

O

H 2a. TsCI, Et,N-benzene,

0 OC

2b. BnBr, CsF-DMF 2c. TBDMSCI-CHCI,

Rl = TBDMS, R2 = H 99%

OH

1. (Bu,Sn),O

FIG. 47.-Reactions

R' = H, R2 = Ts 72% R1 = H, R2= Bn 70%

-

OH

of dibutylstannylene a c e t a l ~ ' ~and " ~ a tributylstannyle ether74 of

two triols.

tions provide more selective reactions for this type of substrate. Numerous examples have appeared in which the CsF conditions yielded mixtures containing small proportions of the secondary products, but no examples have been noted in which the latter conditions yielded mixtures. Figure 49 shows an example of methylation of a sensitive substrate under the latter condition^.^'' Dibutylstannylene acetals and tributylstannyl ethers of terminal 1,3-diols also react preferentially with most electrophiles on the terminal oxygen atom. The terminal 1,3-diol can be acyclic, or the secondary oxygen atom can be on a ring adjacent to an hydroxymethyl group, such as 0 - 4 and 06 of aldohexopyranoses or 0 - 3 and 0- 5 of aldopentofuranoses. Figures 50 to 53 show some examples. C&OBn HO 4 ' O H

1 . BySnO y

r

OH CyOH

162 FIG.4d.-Benzylation

*

2

2. BnBr, Bu,NBr

-

toluene, 70 "C, 5h

Hoi 7%

POH

CH,OBn

60%

of the dibutylstannylene acetal of 3,4-dideoxy-~-rhreo-hexitol.'"'~~

122

T. BRUCE GRINDLEY

pvoMe

Bn I

1. Bu,SnO

C0,Me

c

2. MeI, Bu,NBr benzene, 100 OC

BzO

I 171

FIG.49.-Methylation vessel?"

OMe

73%

OMe

of the dibutylstannylene acetal of a Kdo derivative in a sealed

I . BySnO

benzene, 0 "C

172

2b. BnBr, Bu,NI benzene, 50 "C

FIG.50.-Reactions

6 OMe

NHAc

OH

-

2. BnBr, Bu,NI-

Ho&/

NHAc OMe

BnO

toluene, 11 I "C

78%

of the tributylstannyl ether of a terminal 1,3-diol from a p-D-

OM.

2. BnBr, Bu,NBr CH,CN, 80 OC

175

R = B n 98%

1. (Bu,Sn),O

OH

N3

-

of the dibutylstannylene acetal of an acyclic terminal 1,3-diol.l2

HO BnO

FIG. 51.-Benzylation glucopyranoside

R = T s 88%

OH

OBn

k

O

M

e

N3

8 1%

FIG.52.-Benzylation of the dibutylstannylene acetal of a terminal 1.3-diol from a 0-0gulopyranoside derivative."'

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

123

OH CH,OTs

OH CH,OH I. B y S n O

b

-b

2. TsCI, Bu,NBr-CHCI,

SPh SPh 86% FIG.53.-p-Toluenesulfonylation of the dibutylstannylene acetal of the terminal 1,3-diol in phenyl 2,3-dideoxy- l-thi0-a-o-rhreo-2-enopyranoside.~"

As previously noted, dibutylstannylene acetals of all compounds that have a free primary hydroxyl group, including such compounds as methyl a-D-mannopyranoside or uridine, which have cis-1,2-diols unprotected, react with t-butylchlorodimethylsilane to give substitution on the primary oxygen atom in high ~ i e l d . There ~ ~ - ~is no evidence of any products of substitution on secondary oxygen atoms in these reactions. Oxidation of both dibutylstannylene acetals76~xz2.30x and tributylstannyl of terminal 1,2- and 1,3-diols with bromine or Nbromosuccinimide occur at the more substituted oxygen atom. The causes of this preference were discussed in Section VI. Two types of reaction conditions from stannylene acetals have been developed that effect preferential substitution on the oxygen at the more substituted carbon atom. The method of Roelens and his co-workers has been applied to a wide range of simple non-carbohydrate 1,2- and 13-diols. The dibutylstannylene acetals of these compounds are treated with benzoyl chloride followed by a chlorosilane, normally chlorodimethyphenylsilane, but chlorotrimethylsilane is nearly as effective (see Fig. 54). The two esterdibutylstannyl ether intermediates from the first stage can equilibrate. The bulky silylating agent has a strong preference for reaction at the primary oxygen atom, and equilibration takes place during the second step of the reaction sequence. Thus, products having the ester on the secondary or tertiary oxygen are obtained, with good r e g i o ~ p e c i f i c i t y It . ~has ~ ~ ~not ~~~~ yet been demonstrated that the dimethylphenylsilyl or trimethylsilyl groups

I . Bu,SnO

H O T P h OH

2 BzCI-CHCI,, RT, Ih

B z 0 y p h

OSiM5Ph 5

3 PhMe$CI-CHCI,, O°C, 1.5 h

FIG.54.-Benzoylation

+

Pm%SiO/YPh OBz 95 (59% isolated)

of 2-phenyl-I.2-enthanediolwith reversed regioselectivity?'R4

T. BRUCE GRINDLEY

124 HO

1. R,SnO D

2. TsCI-CHCI,

R=Bu 2R=(C&),

43% 5%

52% 91%

FIG. 55.-Tosylation of 3-O-benzyl-l,2-O-isopropylidene-cr-~-glucofuranose with reversed regioselectivity?"

can be removed without causing isomerization of the ester. For some substrates, oxalic acid in chloroform, which is presumably an aggregate, also gives preferential quenching at the primary center. A second method can be used for p-toluenesulfonylation reactions performed in the absence of added nucleophiles. As outlined in Section VI, dialkylstannylene acetals of terminal 12-diols are present mainly as dimers that have the secondary oxygen atom dicoordinate, and thus these oxygen atoms are more nucleophilic. In other less populated dimers, the primary oxygen atom is dicoordinate, and its inherently greater reactivity than the secondary oxygen atom makes this less populated dimer more reactive. If the population of the more populated dimer is sufficiently greater than that of the less populated (but more reactive) dimer, reaction at the secondary oxygen atom is preferred. These conditions are not met with dibutylstannylene acetals, but use of hexamethylenestannylene acetals leads to substitution on the secondary oxygen atoms with fair to excellent regioselectivity, depending on the substrate (see Fig. 55).'9.20337The starting materials for the latter type of stannylene acetal, hexamethylenetin oxide, is not available commercially but can be prepared conveniently.2' 6. Glycoside Formation

Some of the most exciting developments in the applications of organotin derivatives to carbohydrate chemistry have come in their use for the synthesis of glycosides. These intermediates have served as both glycosyl donors and glycosyl acceptors. Applications in the former area are discussed first and are listed in Table X. 1,2-cis-Methyl glycosides have been formed in variable yields from partially protected free sugars.224,325,326 For instance, the dibutylstannylene reacts with methyl iodide in acetal of 3,4,6-tri-0-benzyl-~-mannopyranose DMF at 45°C to give the 6-glycoside in 94% yield, or with ally1 bromide

TABLEX Glycoside Formation Using Dibntylstannylene Acetals as Glycosyl Donors Yield (YO)

Reaction Conditions Compound

Solvent

Nuc."

DMF 3,4,6-Tri-O-benzyl-~-mannopyranose 3,4.6-Tri-O-benzyl-o-mannopyranose DMF 3,4,6-Tri-O-benzyl-~-mannopyranose Benzene TBAI 3,4.6-Tri-O-benzyl-~-gIucopyranose DMF 3,5-Di-O-benzyl-~-ribofuranose DMF 3,5-Di-O-benzyl-o-ribofuranose KzC03 DMF Pyridine o-Mannose 4,rid in e D-Mannose Pyridine L-Rhamnose Pyridine L-Rhamnose Pyridine D-Lyxose 6-0-Trityl-D-talose Pyridine CH&N BbNF 3-O-Benzyk-~-mannose

Temp. ("C) 45 75 80 45 38 Amb. Amb. Amb. Amb. Amb. Amb. Amb. 25

3-O-Benzyl-o-mannose

DMF

CsF

25

D-Mannose

CH3CN

Bu~NF

25

o-Mannose

DMSO

L-Rhamnose

DMF

CsF

-5

L-Rhamnose

DMF

CsF

25

25

Electrophile

a

0 Methyl iodide 0 Ally1 bromide 0 Benzyl bromide 10 Methyl iodide 49 Methyl iodide 83 Benzyl bromide 0 Acetic anhydride 0 Benzoyl chloride 0 Acetic anhydride 0 Benzoyl chloride 0 Acetic anhydride 0 Acetic anhydride Methyl 2,3,4-tri-O-benzoyl-6-0-triflyl-a-~- 0 glucopyranoside Methyl 2,3,6-tri-O-benzoyl-4-0-triflyl-a-~0 galactopyranoside Methyl 2,3,4-tri-O-benzoyl-6-0-tnflyl-a-o0 glucopyranoside 0 Methyl 2.3,6-tri-0-benzoyl~-O-triflyl-a-~galactopyranoside 0 Methyl 2,3,4-tri-O-benzoyl-6-O-triflyl-a-~glucopyranoside Methyl 2,3,6-tn-O-benzoyl-4-0-triffyl-cY-~- 0 galactopyranoside

Added nucleophile; for abbreviations of nucleophile names, see Table IV. F'yranose form isolated as the pentaacetate. Pyranose form isolated as the pentabenzoate. Pyranose form isolated as the tetraacetate. ' 1.2.3,5-Tetra-O-acetyl-6-O-tntyl-~-~-talofuranose was accompanied by 13%of the a-furanose anomer.

p

Other

Ref.

94

0 0 0 2 70 243 2 13

224 224 325 224 326 326 327 327 327 327 327 327 230

Loo 70 0 0 0 85 72' 95 9w 85d 40d 75

8-f 13'

65

230

57

230

59

230

88

230

78

230

126

T. BRUCE GRINDLEY

at 75°C to give the P-glycoside in 100%yield.224However, the dibutylstannylene acetal of 3,4,6-tri-0-benzyl-~-glucopyranose, on treatment with methyl iodide in DMF at 45"C, mainly gives the 2-methyl ether (70% yield) and only 10% of the 1,2-cis-glycoside,the (Y a n ~ m e r . ~ ~ ~ cis-Glycosyl esters, either acetates or benzoates, can be formed with good stereochemical control from free sugars having axial hydroxyl groups at C2 by reaction of the dibutylstannylene acetals, formed in methanol, with acetic anhydride or benzoyl chloride in ~ y r i d i n e . ~ The '~ 1,2-0dibutylstannylene acetal is probably the major species present in solution,'27 but this useful result presumably arises because 0-1 in this species is the most nucleophilic oxygen atom in the mixture of stannylene acetals present (see Fig. 56). These reactions give mixtures if 0 - 2 is oriented e q ~ a t o r i a l l y . ~ ~ ~ A most promising development is the observation that dibutylstannylene acetals of L-rhamnose and D-mannose derivatives having 0-1 and 0 - 2 unprotected react with primary and secondary triflates of sugars under mild conditions to give in good yields cis-(1+2)-linked disaccharides with inversion in the glycosyl acceptor (see Fig. 57).230As noted in Table X, L-rhamnose derivatives give better yields than shown for the mannose derivatives in Fig. 57. Tributylstannyl and dibutylstannylene derivatives have also been employed as glycosyl acceptors. In particular, tributylstannyl groups have often been used to increase the nucleophilicity of oxygen and sulfur atoms. Simple alkyl and aryl glycosides and thioglycosides can.be prepared in useful yields by reaction of glycosyl acetates, halides, or sulfoxides with tributyltin ethers and thioethers in the presence of such Lewis acids as trimethylsilyl trifluoro m e t h a n e ~ u l f o n a t e or ~ ~tin '~~~~ The reaction has been applied to the synthesis of S-glycosylatedpep tide^.^^ Dibutyltin derivatives [ B u ~ S ~ ( S RR) = ~ ,Ph, Me, cyclohexyl,t-Bu; Bu2Sn(SePh),] have also been found to react in the same way, particularly when Bu2Sn(0Tf)* is used as the Lewis acid catalyst.336 Glycosyl acetates react with tributyltin methoxide to give glycosyl tributylstannyl ethers. As with glycosyl anions,337-339 the anomeric effect causes

PH c''lOri~ B

"

W

J

,

B ' O

U

z

~

W

Pyridine OBz

'Bu Bu

90%

Bu FIG.

O

56.-Formation of a cis-glycosyl ester from a dibutylstannylene acetal.'*'

B

z

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

H HO O

1. BySnO

a

O

BzO %

Bz 0

59%

Bz.0 BZO

127

OMe

I OMe

DMSO. 25 "C, 48 h

1 Bu,SnO

* HBnO O

a

O

%

BzO BzO

67%

Bz 0

DMF, CsF, 25 "C, 18 h FIG.57.-Formation of cb-1,2-linked disaccharides by reactions of glycosyl dibutylstannylene acetals with secondary triflate~.~~"

the axial orientation to be favored. Hydrolysis on workup is then a convenient method for freeing the anomeric center of a poly-0-acetyl derivative for conversion into a more reactive glycosyl d ~ n o r . ~Reaction ~ ' , ~ ~ with allyl acetate in the presence of catalytic palladium(0) compounds gives allyl glycosides with predominant retention of anomeric configuration, even in the presence of participating This type of reaction has also been used for the formation of disaccharides and oligosaccharides. Liu and Danishefsky have achieved very good regioselectivity for the primary oxygen atom in the reaction of the tributylstannyl ether of a terminal, 1,3-diol with a glycosidic oxirane in the presence of a Lewis acid catalyst, Zn(OTf)*, and also obtained good trunsstereoselectivity (see Fig. 58).343A number of other examples of this type of reaction have appeared, using this and other active glycosyl don o r ~ . ~ ~ ~Choice - ~ ~ of ' *a~different ~ " . ~ Lewis ~ ~ acid can lead to cis-(1+2) glycosidic linkages (Fig. 59).344In an interesting application, Danishefsky et ~ 1 . ~have ~ ' reacted tributylstannyl ethers derived from 6-0-tbutyldimethylsilyl-D-galactal and 6,6'-di-O-t-butyldimethylsilyl-lactalwith glyglycal-derived iodosulfonamides to give trans-2-deoxy-2-sulfonylamino

OMe

T. BRUCE GRINDLEY

128

TESo

a

A

1. 2,2-Dimethyldioxirane acetone, 0 "C

o

~

TESO

b

y3

OTES

2. 2eq. B

u

,

S

n

I OH

O\ w (CHZ),*CH,

2 eq. Zn(OTf), -THF, 0 "C to RT

oms TESO

TESO OTES

OH

OH 44% after desilylation and acetylation

FIG.58.-Formation of a fruns-(l-+ 2)-linked glycoside by a Lewis acid-catalyzed reaction of a glycosyl oxirane with a tributyltin either.'4'

cosides in yields of 52 and 42%,respectively (Fig. 60). It should be emphasized that, in most of these reactions, the role of the tributyltin ether is simply to enhance the nucleophilicity of the ethereal oxygen, and tributylstannyl ethers are used only when the reaction with the alcohol is slow.346 Peracetylated and perbenzylated glycosyl chlorides and acetates were investigated some years ago as glycosyl donors toward dibutylstannylene

&

N 3

2 eel

B Y s n o ~ ( c % ) , , c % OH

BnO BnO

0

2 eq. AgBF4- THF, 0 "C to RT b

BnO BnO

y3

o-i--(c%)'2cq OH

41% after acetylation

FIG.59.-Formation of a cis-( 1+2)-linked glycoside by a silver tetrafluoroborate-catalyzed reaction of glycosyl oxirane with a tributyltin either.j4'

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

129 OTBDMS

AcO AcO

10 eq.

I OBn

Bn 0

- %:& 5 eq. AgBF,

OTBDMS

AcO

AcO

THF

AcO

OAC

:&

I

I

NHR

52%

Bn 0

FIG.60.-Reaction of tributylstannyl ethers with iodos~lfonamides~~’

acetals, both in the absence and presence of Lewis acids, but the results were mixed.347In a few cases, disaccharides and trisaccharides were obtained, but, in the case of peracetates, orthoesters were often the major products and the products obtained were the same as those formed in the absence of organotin activation. However, it has since been demonstrated that (1+6)-glycosyl linkages can be formed efficiently in this manner. Martin-Lomas and his co-workers used the tributylstannyl ether of methyl P-lactoside as a glycosyl acceptor, with 2,3,4,6-tetra-O-benzyl-au-~-galactosyl bromide in toluene containing tetraethylammonium bromide, to give the a-(1+6)-linked trisaccharide in 58% yield plus a further 14% of the a-(1+6)-linked trisaccharide and also glycosylated 1,6-anhydro-P-~-galactopyranose.~~* Subsequently, Garegg et al. demonstrated that this procedure is general; dibutystannylene acetals of methyl a- and 0-D-galactopyranosides and methyl j3-D-glucopyranosides act as glycosyl acceptors toward glycosyl halides, with tetrabutylammonium iodide and glycosyl thioglycosides activated by DMTST, to form (1-6)linkages in yields of 4441% (see Figs. 61 and 62).349 7. Miscellaneous

Table XI lists results on acyclic diols whose structures cannot be characterized into one of the foregoing categories. The observations on the benzylation of the dibutylstannylene acetal of 2,3-dihydroxybutanoic acid derivatives in DMF in the presence of cesium fluoride, where more product is

130

T. BRUCE GRINDLEY

&

BnO BnO

OBn Bu,SnOOMe MeOH, reflux

HO

Bu,NI-CH,CI,, RT, 4 days

-

OH

Br

c

BnO BnO OHO O

78% "

N

k

O

M

e

OH

FIG.61.-Formation of a (1+6)-linked disaccharide by reaction of a dibutylstannylene acetals of unprotected glycosides with a glycosyl br0rnide.3~'

&

SEt

AcO AcO

-

B%snoOMe MeOH, reflux

HO

OH

DIVITST -CH,CI,, RT, 10 h

NPhth

C

, OAc

AcO NPhth HO 81%

OMe OH

FIG.62.-Formation of a (1+6)-linked disaccharide by reaction of a dibutylstannylene acetal of an unprotected glycoside with a thioglycoside and DMTST?5'

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

131

obtained on 0-3, is probably due the greater nucleophilicity of this oxygen atom in the monocoordinated dimer, although the original authors offered a different explanation>' The preference for reaction on 0 - 4 of 2-methyl2,4-pentanediol is simply due to steric hindrance. The results on benzoylation of the dibutylstannylene acetal of 5-0benzoyl-L-arabinose dialkyl dithioacetals and related compounds are interesting (see Fig. 63).350For the dialkyl dithioacetals and for the benzyloxime, there is a marked preference for reaction at 0-4, adjacent to the existing benzoyl group, followed by reaction at 0-2, adjacent to the C-1 group. The first preference is similar to that noted earlier for P-D-xylopyranoside derivatives, where replacement of a 4-0-benzyl group by a 4-0-benzoyl group caused the regioselectivity of the reaction to change drastically from close to a 1 : l mixture to reaction exclusively at 0-3.'32 However, the regioselectivity of these reactions on acyclic diols may be controlled by the rate of quenching.53Therefore, comparison with direct benzoylation may be more relevant, and it is interesting that preferences for the direct reaction are similar: For example, D-galactose diethyl dithioacetal forms the 5,6-dibenzoate, and then the 2,5,6-tri-benzoate under these ~onditions.3~~ In the dibutylstannylene acetal reaction, replacement of a dialkyl dithioacetal by a dimethyl acetal reverses the two regioselectivitiesjust mentioned, in line with the argument on electron-withdrawing effects. An interesting reaction that does not fit into any of these categories has been reported by Hodosi and K o v ~ i EThey . ~ ~ noted that, when aldoses and ketoses having 0 - 2 unprotected are heated at >60°C for an extended period of time (2 to 24 h) with dibutyltin oxide in methanol, ethanol, or benzene, epimerization occurs at C-2.73The products obtained contain much more of those compounds having 0-2 in an axial orientation than would be expected on thermodynamic grounds, and also more than that obtained in

WR),

HO{ HO

CHCR),

OH

1 . Bu,SnO 2. BzCI- benzene

HOToR1 R20

C%OH

CqOH

179

R-SEt

R = S E t R ' = H R 2 = B z 75%

180

R=OMe

R = O M e R 1 = B z R 2 = H 97%

FIG. 63.-Benzoylation arabinose?'*

of dibutylstannylene acetals of acyclic triols derived from L-

TABLE XI Reactions of Dibutylstannylene Acetals and Tributyltin Ethers of Acyclic Polyols

Compound

Solvent

Nuc

Temp. ("C)

Methyl (2S,3R)-2,3-dihydroxybutanoate N,N-Dimethyl (2S,3R)-2,3-dihydroxybutanamide 2-Methyl-2,4-pentanediol 5-O-Benzoyl-~-arabinosediethyl dithioacetal (179)

Acetal Acetal Acetal Acetal

DMF DMF DMF Benzene

CsF CsF CsF

Amb. Amb. Amb. Amb.

Acetal

Benzene

Amb.

Acetal

Benzene

Amb.

Acetal

Benzene

Amb.

5-O-Pivaloyl-~-arabinosediethyl dithioacetal

Acetal

Benzene

Amb.

5-O-Benzoyl-~-arabinosebenzyloxime 5-O-Benzoyl-~-arabinosedimethvl acetal (180)

Acetal Acetal

Benzene Benzene

Amb. Amb.

5-0-Benzoyl-L-arabinose dibenzyl dithioacetal

Yield (YO)

Reaction Conditions

A c e d or Ether

Electrophile

Site 1

Benzyl iodide 0 - 2 30 Benzyl iodide 0 - 2 17 Benzyl iodide 0-2 0 Benzoyl chloride 0 - 4 75 (1 equiv) Benzoyl chloride (2 equiv) Benzoyl chloride 0-480 (1 equiv) Benzoyl chloride (2 equiv) Benzoyl chloride 0 - 2 18 (1 equiv) 0-4 23 Benzoyl chloride 0-4 91 Benzovl chloride 0 - 2 97

Site2

Ref.

0 - 3 55 0-3 75 0-450 2.4-Di-12

69 69 69 350

2,4-Di 98

350

2.4-Di 8

350

2.4-Di 98

350

2,4-Di 29

350

2.4-Di 4

350 350

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

133

epimerization using molybdenum salts.352-354 This observation most likely arises from equilibration of the dibutylstannylene acetals, which are most stable if 0-1 and 0 - 2 are cis. Thus, epimerization of 6-O-trityl-~-galactose gave 6-O-trityl-~-talosein yields of 60-70%?3

REFERENCES (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) (29) (30) (31) (32)

D. Wagner, J. P. H. Verheyden, and J. G. Moffatt, J. Org. Chem. 39 (1974) 24-30. S. David, C. R. Acad. Sci., Ser. C, 278 (1974) 1051-1053. S. David and S. Hanessian, Tetrahedron, 41 (1985) 643-663. M. Pereyre, J. P. Quintard, and A. Rahm, Tin in Organic Synthesis, Chap. 11. Butterworths, London, 1987. S. J. Blunden. P. A. Cusack, and P. J. Smith, J. Organomet. Chem. 325 (1987) 141-152. T. B. Grindley, in P.KovaE (Ed.), Synthetic Ofigosaccharides: Indispensable Probes for the Life Sciences. Chap. 4. ACS, Washington, D.C., 1994. S . David, in S. Hanessian (Ed.), Preparative Carbohydrate Chemistry, Chap. 4. Marcel Dekker, New York, 1996. Nomenclature of Carbohydrates, Pure Appf. Chem., 68 (1996) 1919-2110 Adv. Carbohydr. Chem. Biochem., 52 (1997) 47-171. 0 . Kjdberg and K. Neumann, Acta Chem. Scand., 47 (1993) 721-727. P. Kovai: and K. J. Edgar, J. Org. Chem., 57 (1992) 2455-2467. G. Yang, F. Kong, and S. Zhou, Carbohydr. Res., 211 (1991) 179-182. G.-J. Boons, G. H. Castle, J. A. Clase, P. Grice, S. V. Ley, and C. Pinel, Synfett (1993) 913-914. G.-J. Boons, G. H. Castle, J. A. Clase, P. Grice, S. V. Ley, and C. Pinel, Synfett (1994) 764. R. A. Barrow, T. Hemscheidt, J. Liang, S. Paik, R. E. Moore, and M. A. Tius, J. Am. Chem. Soc. 117 (1995) 2479-2490. A. Morcuende, S. Valverde, and B. Herradon, Synfett (1994) 89-91. B. Herradon, A. Morcuende, and S. Valverde, Synfert (1995) 455-458. A. Morcuende, M. Ors, S. Valverde. and B. Herradbn, J. Org. Chem., 61 (1996) 52645270. C. W. Holzapfel, J. M. Koekemoer, and C. F. Marais, S. Afr. J. Chem. 37 (1984) 19-26. T. B. Grindley and X. Kong, Tetrahedron Lett., 34 (1993) 5231-5234. X. Kong and T. B. Grindley, Can. J. Chem., 72 (1994) 2396-2404. X. Kong and T. B. Grindley, P. K. Bakshi, and T. S. Cameron, Organometaffics,12 ( 1993) 4881-4886. V. S. Petrosyan, Progress NMR Spectrosc. 11 (1977) 115-148. P. J. Smith and A. P. Tupciauskas, Ann. Rep. NMR Spectrosc., 8 (1978) 291-370. B. Wrackmeyer. Ann. Rep. NMR Spectros., 16 (1985) 73-186. J. D. Kennedy and W. McFarlane, in J. Mason (Ed.), Multinucfear NMR, Chap. 11. Pergamon Press, London, 1988. Y. K. Puskar, T. A. Saluvere, E. T. Lippmaa, A. B. Permin, and V. S. Petrosyan, Dokl. Akad. Nauk. SSR, 220 (1997) 19-21. R. R. Sharp, J. Chem. Phys., 57 (1972) 5321-5330. R. R. Sharp, J. Chem. Phys., 60 (1974) 1149-1157. C. R. Lassigne and E. J. Wells, Can. J. Chem., 55 (1977) 927-931. S. Chapelle and P. Granger, J. Mugn. Reson., 76 (1988) 1-13. A Laakonsen and R. E. Wasylishen, J. Am. Chem. Soc. 117 (1995) 392-400. S. J. Blunden, A. Frangou, and D. G. Gillies, Org. Magn. Reson. 20 (1982) 170-174.

134

T. BRUCE GRINDLEY

(33) T. B. Grindley, R. D. Curtis, R. Thangarasa, and R. E. Wasylishen, Can. J. Chem. 68 (1990) 2102-2109. (34) P. J. Smith, R. F. M. White, and L. Smith, J. Organomet. Chem., 40 (1972) 341-353. (35) S. J. Blunden, P. J. Smith, P. J. Beynon, and D. G. Gillies, Curbohydr. Res., 88 (1981) 9-18. (36) C. Cruzado, M. Bernabe, and M. Martin-Lomas, J. Org. Chem., 54 (1989) 465-469. (37) X. Kong and T. B. Grindley, Can. J. Chem. 72 (1994) 2405-2415. (38) T. B. Grindley and R. Thangarasa, J. Am. Chem. SOC.112 (1990) 1364-1373. (39) T. B. Grindley, R. E. Wasylishen, R. Thangarasa, W. P. Power, and R. E. Curtis, Can. J. Chem., 70 (1992) 205-217. (40) P. A. Bates, M. B. Hursthouse, A. G. Davies, and S. D. Slater, J. Organornet. Chem., 363 (1989) 45-60. (41) R. Thangarasa and T. B. Grindley, unpublished results. (42) T. B. Grindley, R. Thangarasa, P. K. Bakshi, and T. S. Cameron, Can. J. Chem., 70 (1992) 197-204. (43) S. David, A. Thieffry, and A. Forchioni, Tetrahedron Lett., 22 (1981) 2647-2650. (44) T. B. Grindley and R. Thangarasa, Can. J. Chem., 68 (1990) 1007-1019. (45) S. KBpper and A. Brandenburg, Liebigs Ann. Chem., (1992) 933-940. (46) J. HoleEek, K. Nidvornik, K. Handlii, and A. LyEka, J. Organomet. Chem. 315 (1986) 299-308. (47) J. Holetek and A. LyEka, Inorg. Chim. Acta, 118 (1986) L15-Ll6. (48) T. P. Lockhart and W. F. Manders, J. Am. Chem. SOC.,109 (1987) 7015-7020. (49) G. Domazetis, R. J. Magee,and B. D. JamesJ. Inorg. Nucl. Chem., 41 (1979) 1547-1553. (50) S. Roelens and M. Taddei, J. Chem. SOC.,Perkin Trans. I1 (1985) 799-804. (51) C. W. Holzapfel, J. M. Koekemoer, C. F. Marais, G. J. Kruger, and J. A. Pretorius, S. Afr. J. Chem., 35 (1982) 80-88. (52) A. G . Davies, A. J. Price, H. M. Dawes, and M. B. Hursthouse, J. Chem. Soc., Dalton Trans. (1986) 297-302. (53) S. Roelens, J. Org. Chem.. 61 (1996) 5257-5263. (54) A. M. Domingos, and G. M. Sheldrick, Acta Crystallogr., Sect. B, 30 (1974) 519-521. (55) N. Kasa, K. Yasuda, and R. Okawara, J. Organornet. Chem., 3 (1965) 172-173. (56) R. K. Harris, K. J. Packer, P. Reams, and A. Sebald, J. Magn. Reson. 72 (1987) 385-387. (57) J. Alais and A. Veyribres, J. Chem. SOC.,Perkin Trans. I (1987) 377-381. (58) J. D. Kennedy, J. Chem. SOC.,Perkin Trans. I1 (1977) 242-248. (59) S. David, C. Pascard, and M. Cesario, Nouv. J. Chim., 3 (1979) 63-68. (60) T. S. Cameron, P. K. Bakshi, R. Thangarasa, and T. B. Grindley, Can. J. Chem., 70 (1992) 1623-1630. (61) C. Luchinat and S. Roelens, J. Org. Chem., 52 (1987) 4444-4449. (62) A. G . Davies and A. J. Price, J. Organornet. Chem., 258 (1983) 7-13. (63) S. David, A. Thieffry, and A. Veyri&res,J. Chem. SOC.,Perkin Trans. I(1981) 1796-1801. (64) S. J. Danishefsky and R. Hungate, J. Am. Chem. SOC., 108 (1986) 2486-2487. (65) N. Nagashima and M. Ohno, Chem. Lett. (1987) 141-144. (66) M. A. Nashed and L. Anderson, Tetrahedron Lerr., 39 (1976) 3505-3506. (67) T. Ogawa and M. Matsui, Carbohydr. Rex, 62 (1987) Cl-C4. (68) C. Cruzado and M. Martin-Lomas, Carbohydr. Res., 175 (1988) 193-199. (69) N. Nagashima and M. Ohno, Chem. P a m . Bull., 39 (1991) 1972-1982. (70) M. E. Haque, T. Kikuchi, K. Kanemitsu, and Y. Tsuda, Chem. Pharm. Bull., 35 (1987) 1016-1029. (71) A. Grouiller, V. Buet, V. Uteza, and G. Descotes, Synlett (1993) 221-222.

APPLICATIONS OF TIN-CONTAINING INTERMEDIATES

135

(72) C. W. Holzapfel, J. J. Huyser, T. L. van der Menve, and F. R. van Heerden, Heterocycles, 32 (1991) 1445-1450. (73) G. Hodosi and P. KovaE, J. Curbohydr. Chem. (1998) in press. (74) T. Ogawa and M. Matsui, Tetrahedron, 37 (1981) 2363-2369. (75) T. Ogawa, Y. Takahashi, and M. Matsui. Curbohydr. Res., 102 (1982) 207-215. (76) S. David and A. Thieffry, J. Chem. SOC., Perkin Trans. I (1979) 1568-1573. (77) Y. Tsuda, M. Hanajima, N. Matsuhira, Y. Okuno, and K. Kanemitsu, Chem. Phurm. Bull., 37 (1989) 2344-2350. (78) H.-M. Liu, Y. Sato, and Y. Tsuda, Chem. Phurm. Bull., 41 (1993) 491-501. (79) A. Martin, M. Pays, and C. Monneret, Curbohydr. Rex, 113 (1983) 21-29. (80) S. David and G. de Sennyey, Curbohydr. Rex, 77 (1979) 79-97. (81) L. den Drijver, C. W. Holzapfel, J. M. Koekemoer, G. J. Kruger, and M. S. van Dyk, Curbohydr. Rex, 155 (1986) 141-150. (82) X. Kong and T. B. Grindley, J. Curbohydr. Chem., 12 (1993) 557-571. (83) S. Roelens. J. Chem. Soc., Perkin Trans. I1 (1988) 2105-2110. (84) G. Reginato, A. Ricci, S. Roelens, and S. Scapecchi,J. Org. Chem., 55 (1990) 5132-5139. (85) V. Gopalakrishnan, H. Mereyala, A. G. Samuel, and K. N. Ganesh, Tetrahedron Lett., 31 (1990) 1613-1614. (86) A. Glen, D. A. Leigh, R. P. Martin, J. S. Smart, and A. M. Truscello, Curbohydr. Res., 248 (1993) 365-369. (87) D. A. Leigh, R. P. Martin, J. S. Smart, and A. M. Truscello, J. Chem. Soc., Chem. Commun. (1994) 1373-1374. (88) M. W. Bredenkamp, S. Afr. J. Chem., 48 (1995) 154-156. (89) A. H. Haines, Adv. Curbohydr. Chem. Biochem., 33 (1976) 11-109. (90) R. Thangarasa, Ph.D. Thesis, Dalhousie University, 1990. Jenkins and B. V. L. Potter, Curbohydr. Res., 265 (1994) 145-149. (91) D. .I. (92) P. J. Garegg, T. Iversen, and S. Oscarson, Curbohydr. Res., 50 (1976) C12-C14. (93) A. Shanzer, Tetrahedron Lett., 21 (1980) 221-222. (94) T. Mukaiyama, I. Tomioka, and M. Shimizu, Chem. Lett. (1984) 49-52. (95) Y.Shibata. Y. Kosuge, and S. Ogawa, Curbohydr. Res., 199 (1990) 37-54. (96) T. Mukaiyama, Y. Tanabe, and M. Shimizu, Chem. Lett. (1984) 401-404. (97) J. AubC, C. J. Mossman, and S. Dickey, Tetrahedron, 48 (1992) 9819-9826. (98) A. V. R. Rao, S. V. Mysorekar, M. K. Gurjar, and J. S. Yadav, Tefruhedron Lett., 28 (1987) 2183-2186. (99) J. S. Yadav, S. V. Mysorekar, S. M. Pawar, and M. K. Gurjar, J. Curbohydr. Chem., 9 (1990) 307-316. (100) G. Gogjoian, V. R. Wang, A. M. Ayala, R. V. Martinez, R. Martinez-Bernhardt, and C. G. GutiCrrez, Tetrahedron Lett., 37 (1996) 433-436. (101) E. A. Mash, L. T. Kantor, and S. C. Waller, Synth. Commun., 27 (1997) 507-514. (102) P. Rochet, J.-M. VatL?le,and J. Gore, Synthesis (1994) 795-799. (103) K. C. Reddy, H.-S. Byun, and R. Bittman, Tetrahedron Lett., 35 (1994) 2679-2682. (104) J. Green and S. Woodward, Synlett (1995) 155-156. (105) R. M. Manavu and H. H. Szmant, J. Org. Chem., 41 (1976) 1832-1835. (106) Y. Tsuda, M. Nishimura, T. Kobayashi, Y. Sato, and K. Kanemitsu, Chem. Phurm. Bull., 39 (1991) 2883-2887. (107) S. Langston, B. Bernet, and A. Vasella, Helv. Chim., Actu, 77 (1994) 2341-2353. (108) T. Ogawa and T. Kaburagi, Curbohydr. Rex, 103 (1982) 53-64. (109) F. Dasgupta and P. J. Garegg, Synthesis (1994) 1121-1123. (110) H. Qin and T. B. Grindley, J. Curbohydr. Chem., 15 (1996) 95-108. (1 11) J. E. T. Corrie, J. Chem. Soc., Perkin Trans. I(1993) 2161-2166.

136

T. BRUCE GRINDLEY

(112) H. H. Baer and X. Wu, Curbohydr. Res., 238 (1993) 215-230. (113) B. Guilbert, N. J. Davis, M. Pearce, R. T. Aplin, and S. L. Flitsch, Tetrahedron: Asymmetry, 5 (1994) 2163-2178. (1 14) A. Fernandez-Mayoralas, M. Bernabe, and M. Martin-Lomas, Tetrahedron, 44 (1988) 4877-4882. (115) D. D. Manning, C. R. Bertozzi, P. Beck, and L. L. Kiessling, J. Am. Chem. Soc., 119 (1997) 3161-3162. (116) T. L. Lowary and 0. Hindsgaul, Curbohydr. Res., 249 (1993) 163-195. (117) M. Nilsson. J. Westman, and C.-M. Svahn, J. Curbohydr. Chem., 12 (1993) 23-37. (1 18) A. Fernandez-Mayoralas, A. Marra, M. Trumtel, A. Veyriirres, and P. Sinay. Curbohydr. Res., 188 (1989) 81-95. (119) P. Fernhndez, J. JimCnez-Barbero, and M. Martin-Lomas, Carbohydr. Res., 254 (1994) 61-79. (120) Z. Zhang and G. Magnusson, J. Org. Chem., 60 (1995) 7304-7315. (121) E. Bousquet, L. Lay, F. Nicotra, L. Panza. G. Russo, and S. Tirendo, Curbohydr. Res., 257 (1994) 317-322. (122) H. Paulsen, F. Reck, and I. Brockhausen, Curbohydr. Res., 236 (1992) 39-71. (123) H. Paulsen, M. Springer, F. Reck, E. Meinjohanns, I. Brockhausen. and H. Schachter, Liebigs Ann. Chem. (1995) 53-66. (124) S. Iacobucci and M. d’Alarcao, Synth. Commun., 24 (1994) 809-817. (125) D.-M. Gou, Y.-C. Liu, and C.-S. Chen. Carbohydr. Rex, 234 (1992) 51-64. (126) K.-L. Yu and B. Fraser-Reid, Tetrahedron Lett., 29 (1988) 979-982. (127) L. Schmitt, B. Spiess, and G. Schlewer, Tetrahedron Lett., 34 (1993) 7059-7060. (128) P. J. Garegg, B. Lindberg, I. Kvarnstrom. and S. C. T. Svensson. Curbohydr. Rex, 173 (1988) 205-216. (129) S.-K. Chung and Y. H. Ryu, Carbohydr. Rex, 258 (1994) 145-167. (130) Y. Tsuda, M. E. Haque, and K. Yoshimoto, Chem. Phurm. Bull., 31 (1983) 1612-1624. (131) M. E. Haque, T. Kikuchi, K. Yoshimoto, and Y. Tsuda, Chem. Phurm. Bull., 33 (1985) 2243-2256. (132) R. F. Helm, J. Ralph, and L. Anderson, J. Org. Chern., 56 (1991) 7015-7021. (133) K. Takeo and K. Shibata, Curbohydr. Res., 133 (1984) 147-151. (134) Z. Zhang and G. Magnusson, J. Org. Chem. 61 (1996) 2383-2393. (135) H. M. Zuurmond, P. A. M. van der Klein, G. A. van der Marel, and J. H. van Boom, Tetrahedron, 49 (1993) 6501-6514. (136) R. Verduyn, M. Douwes, P. A. M. van der Klein, E. M. Mosinger, G. A. van der Marel. and J. H. van Boom, Tetrahedron, 49 (1993) 7301-7316. (137) V. Pedretti, A. Veyrikres, and P. Sinay, Tetrahedron, 46 (1990) 77-88. (138) K. Takeo, T. Nakaji, and K. Shinmitsu, Carbohydr. Rex, 133 (1984) 275-287. (139) R. Tsang and B. Fraser-Reid, J. Org. Chem., 57 (1992) 1065-1067. (140) C. W. Holzapfel, J. M. Koekemoer, and C. F. Marais. S. Afr. J. Chem., 37 (1984) 57-61. (141) Y. Ichikawa, R. Monden, and H. Kuzuhara, Curbohydr. Rex, 172 (1988) 37-64. (142) A. Fernandez-Mayoralas and M. Martin-Lomas, Carbohydr. Res., 154 (1986) 93-101. (143) D.-M. Gou and C.-S. Chen, Tetrahedron Lett., 33 (1992) 721-724. (144) N. Chida, M. Yoshinaga, T. Tobe, and S. Ogawa, J. Chem. Soc., Chem. Comrnun. (1997) 1043-1044. (145a) T. B. Grindley and R. Thangarasa, Curbohydr. Rex, 172 (1988) 311-318. (145b) T. B. Grindley and H. Namazi, Tetrahedron Lett., 37 (1996) 991-994. (145c) H. Namazi and T. B. Grindley, Can. J. Chem., 75 (1997) 983-995.

APPLICATIONS O F TIN-CONTAINING INTERMEDIATES

137

(146) S.-K. Chung, Y. Ryu, Y.-T. Chang, D. Whang, and K. Kim, Carbohydr. Rex, 253 (1994) 13-18. (147) S. J. Lee, S. J. Cho, K. S. Oh, C. Cui, Y. Ryu, Y.-T. Chang, K. S. Kim, and S.-K. Chung, J. Phys. Chem., 100 (1996) 10111-10115. (148) Y. Ichikawa, R. Monden, and H. Kuzuhara, Tetrahedron Len., 27 (1986) 611-614. (149) T. B. Grindley, A. Cude, J. Kralovic, and R. Thangarasa, in Z. J. Witczak (Ed.), Levoglucosenone and Levoglucosun, Chemistry and Applications, Chap. 11. ATL Press, Mount Prospect, IL, 1994. (150) T. Nakano, Y. Ito, and T. Ogawa, Curbohydr. Res., 243 (1993) 43-69. (1.51) H. Qin and T. B. Grindley, J. Curbohydr. Chern., 13 (1994) 475-490. (152) D. J . Jenkins and B. V. L. Potter, Curbohydr. Res., 287 (1996) 169-182. (153) K. Koch and R. J. Chambers, Curbohydr. Res., 241 (1993) 295-299. (1.54) J. Gigg, R. Gigg, and E. Martin-Zamora, Tetrahedron Lett., 34 (1993) 2827-2830. (155) G. Blatter and J.-C. Jacquinet, Curbohydr. Rex, 288 (1996) 109-125. (156) T. Ogawa. S. Nakabayashi, and K. Sasajima, Curbohydr. Res. 96 (1981) 29-39. (157) K. Takeo and S. Tei, Curbohydr. Res., 141 (1985) 159-164. (158) R. H. Furneaux, G. J. Gainsford, J. M. Mason, P. C. Tyler, 0. Hartley, and B. G. Winchester, Tetrahedron, 51 (1995) 12611-12630. (159) R. H. Youssef, B. A. Silwanis, R. I. El-Sokkary, A. S. Nematalla, and M. A. Nashed, Curbohydr. Rex, 240 (1993) 287-293. (160) R. D. Groneberg, T. Miyazaki. N. A. Stylianides, T. J. Schulze, W. Stahl, E. P. Schreiner, T. Suzuki, Y. Iwabuchi, A. L. Smith, and K. C. Nicolau, J. Am. Chem. Soc., 115 (1993) 7593-761 1. (161) J.-C. Jacquinet and P. Sinay. Curbohydr. Rex, 159 (1987) 229-253. (162) C. Vogel. W. Steffan, A. Y.Ott, and V. I. Betaneli, Carbohydr. Res., 237 (1992) 115-129. (163) J. E. M. Basten, C. A. A. van Boeckel, G. Jaurand, G. Petitou, N. M. Spijker, and P. Westerduin, Bioorg. Med. Chem Lett., 4 (1994) 893-898. (164) V. Pozsgay and H. J. Jennings, Curbohydr. Res., 197 (1988) 61-75. (165) H. M. Zuurmond, G. H. Veeneman, G. A. van der Marel, and J. H. van Boom, Crrrbohydr. Res., 241 (1993) 153-164. (166) K. Zegelaar-Jaarsveld, G. A. van der Marel, and J. H. van Boom, Tetrahedron, 48 (1992) 10133-10148. (167) P. Wetzel, H. P. Bulian, A. Maulshagen, D. Muller, and G. Snatzke, Tetrahedron, 40 (1984) 3657-3666. (168) M. A. Nashed and L. Anderson, Curbohydr. Rex, 56 (1977) 419-422. (169) M. A. Nashed, M. S. Chowdhary, and L. Anderson, Curbohydr. Res., 102 (1982) 99-110. (170) M. A. Nashed and L. Anderson, Curbohydr. Res., 56 (1977) 325-336. (171) H. A. El-Shenaway and C. Schuerch, Curbohydr. Res., 131 (1984) 227-238. (172) C. AugC, S. David and A. Veyrikres, J. Chem. SOC. Chem. Commun. (1976) 375-376. (173) U. Moller, K. Hobert, A. Donnerstag, P. Wagner, D. Muller, H. W. Fehlhaber, A. Markus, and P. Welzel, Tetrahedron, 49 (1993) 1635-1648. (174) K. Takeo, G. 0. Aspinall, P. J. Brennan, and D. Chatterjee, Curbohydr. Res., 150 (1986) 133-150. (175) H. H. Baer. F. H. Mateo, and L. Siemsen, Curbohydr. Res., 187 (1989) 67-92. (176) P. Smid, G. A. de Ruiter. G. A. van der Marel, F. M. Rombouts, and J. H. van Boom, J . Cnrbohydr. Chem., 10 (1991) 833-849. (177) M.-H. Du. U. Spohr, and R. U. Lemieux, GlycoconjuguteJ., 11 (1994) 443-461. (178) F.-Y. Dupradeau, J . Prandi, and J. M. Beau, Tetrahedron, 51 (1995) 3205-3220. (179) V. Ferro, B. W. Skelton, R. V. Stick, and A. H. White, Austral. J. Chem. 46 (1993) 787-803.

138

T. BRUCE GRINDLEY

(180) S.-H. Chen, R. F. Horvath, J. Joglar, M. Fisher, and S. J. Danishefsky, J. Org. Chem., 56 (1991) 5834-5845. (181) C. W. Slife, M. A. Nashed, and L. Anderson, Carbohydr. Rex, 93 (1981) 219-230. (182) T. K. Park, I. J. Kim, S. H. Hu, M. T. Bilodeau, J. T. Randolph, 0. Kwon, and S. J. Danishefsky, J. Am. Chem. Soc., 118 (1996) 11488-11500. (183) A. Lubineau and R. Lemoine, Tetrahedron Lett., 35 (1994) 8795-8796. (184) S.4. Nishimura, S. Murayama, K. Kurita, and H. Kuzuhara, Chem. Lett. (1992) 14131416. (185) D. D. Manning, C. R. Bertozzi, S. D. Rosen, and L. L. Kiessling, Tetrahedron Lett., 37 (1996) 1953-1956. (186) W. Liao, Y. Liu, and D. Lu, Carbohydr. Res., 260 (1994) 151-154. (187) P. Mu, M. Fujie, and Y. Matsui, Bull. Chem. Soc. Jpn., 66 (1993) 2084-2087. (188) P. KoviE, C. P. J. Glaudemans, and R. B. Taylor, Carbohydr. Rex, 142 (1985) 158-164. (189) K. Kohata, S. A. Abbas, and K. L. Matta, Curbohydr. Res., 132 (1984) 127-135. (190) U. Nilsson, A. K. Ray, and G. Magnusson, Carbohydr. Res., 252 (1994) 117-136. (191) J. Alais, A. Maranduba, and A. Veyrikres, Tetrahedron Lett.. 24 (1983) 2383-2386. (192) F. A. W. Koeman, J. W. G. Meissner, H. R. P. van Ritter, J. P. Kamerling, and J. F. G. Vliegenthart, J. Carbohydr. Chem., 13 (1994) 1-25. (193) T. Ekberg and G. Magnusson, Curbohydr. Res., 246 (1993) 119-136. (194) H. Shimizu, Y. Ito, 0.Kanie. and T. Ogawa, Bioorg. Med. Chem. Lett., 6 (1996) 28412846. (195) A. Lubineau, J. Le Gallic, and R. Lemoine,J. Chem. Soc., Chem. Commun. (1993) 14191420. (196) J. M. Coteron, K. Singh, J. L. Asensio, M. Dominguez-Dalda, A. Fernindez-Mayoralas, J. Jimtnez-Barbero, M. Martin-Lomas, J. Abad-Rodriguez. and M. Nieto-Sampedro, J. Org. Chem., 60 (1995) 1502-1519. (197) S. K. Das, R. Ghosh, and N. Roy, J. Carbohydr. Chem. 12 (1993) 693-701. (198) J. C. Prodger, M. J. Bamford, P. M. Gore, D. S. Holmes, V. Saez, and P. Ward, Tetrahedron Lett., 36 (1995) 2339-2342. (199) L. A. Mulard, P. KoviE, and C. P. J. Glaudemans, Curbohydr. Res., 251 (1994) 213-232. (200) A. K. M. Anisuzzaman, L. Anderson, and J. L. Navia, Curbohydr. Res., 174 (1988) 265 -278. (201) M. A. Nashed, Carbohydr. Res., 60 (1978) 200-205. (202) A. Arasappan and B. Fraser-Reid, J. Org. Chem., 61 (1996) 2401-2406. (203) X. Wu and F. Kong, Carbohydr. Rex, 162 (1987) 166-169. (204) M. K. Gurjar and K. R. Reddy, J. Chem. SOC.,Perkin Trans. I(1993) 1269-1272. (205) G. 0. Aspinall and K. Takeo, Carbohydr. Res., 121 (1983) 61-77. (206) S. Kosemura, S. Yamamura, J. Amano, J. Mizutani, and K. Hasegawa, Tetrahedron Lett., 34 (1993) 2653-2656. (207) N. Hong, M. Funabashi, and J. Yoshimura, Carbohydr. Res., 96 (1981) 21-28. (208) R. Mahajan, S. Dixit, N. K. Khare, and A. Khare, J. Carbohydr. Chem., 13 (1994) 63-73. (209) M. K. Gurjar and A. S. Mainkar, Tetrahedron, 48 (1992) 6729-6738. (210) R. L. Halcomb, S. H. Boyer, M. D. Wittman, S. H. Olson, D. J. Denhart, K. K. C. Liu, and S. J. Danishefsky, J. Am. Chem. Soc., 117 (1995) 5720-5749. (211) R. L. Halcomb, S. H. Boyer, and S. J. Danishefsky, Angew. Chem. Inr. Ed. Engl., 31 (1992) 338-340. (212) M. K. Gurjar and U. K. Saha, Bioorg. Med. Chem. Lett., 3 (1993) 697-702. (213) A. Borbis and A. Liptik, Carbohydr. Res., 241 (1993) 99-116. (214) M. J. Eis and B. Ganem, Carbohydr. Res., 176 (1988) 316-323. (215) P. J. Garegg, L. Olson, and S. Oscarson, J. Carbohydr. Chem., 12 (1993) 955-967.

APPLICATIONS O F TIN-CONTAINING INTERMEDIATES

139

(216) T. Oshitari, M. Tomita, and M. Kobayashi, Tetrahedron Lett., 35 (1994) 6493-6494. (217) T. Oshitari and S. Kobayashi, Tetrahedron Lett., 36 (1994) 1089-1092. (218) K. Zegelaar-Jaarsveld, H. K. Duynstee, G. A. van der Marel, and J. H. van Boom, Tetrahedron, 52 (1996) 3575-3592. (219) K. Zegelaar-Jaarsveld, S. A. W. Smits, N. C. R. van Straten, G. A. van der Marel, and J. H. van Boom, Tetrahedron, 52 (1996) 3593-3608. (220) R. Lau, G. Schtile, U. Schwaneberg, and T. Ziegler, Liebigs Ann. Chem. (1995) 17451754. (221) S.-H. Kim, D. Augeri, D. Yang, and D. Kahne,J. Am. Chem. Soc., 116(1994) 1766-1775. (222) H. M. Zuurmond, P. A. M. van der Klein, J. de Wildt, G. A. van der Marel, and J. H. van Boom, J . Carbohydr. Chem., 13 (1994) 323-339. (223) A. J. Varma and C. Schuerch, J. Org. Chem., 46 (1981) 799-803. (224) V. K. Srivastava and C. Schuerch, Tetrahedron Lett., 35 (1979) 3269-3272. (225) Y. Shin, K. H. Chun, J. E. N. Shin, and G. 0. Aspinall, Bull. Kor. Chem. Soc., 16 (1995) 625-630. (226) S. S. Rana, J. J. Barlow, and K. L. Matta, Carbohydr. Res., 85 (1980) 313-317. (227) W. B. Severn and J. C. Richards, J. Am. Chem. Soc., 115 (1993) 1114-1120. (228) P. Kovif, Carbohydr. Rex, 245 (1993) 219-231. (229) P. K. Richter. M. J. Tomaszewski, R. A. Miller, A. P. Parton, and K. C. Nicolaou, J . Chem. Soc., Chem. Commun. (1994) 1151-1155. (230) G. Hodosi and P. KovAE, J. Am. Chem. Soc., 119 (1997) 2335-2336. (231) H. Namazi and T. B. Grindley, unpublished results. (232) F. Dasgupta and P. J. Garegg, Synthesis (1989) 626-628. (233) M. K. Gurjar and U. K. Saha, Tetrahedron Lett., 33 (1992) 4979-4982. (234) R. Baker, J. J. Kulagowski, D. C. Billington, P. D. Leeson, I. C. Lennon, and N. Liverton, J. Chem. Soc., Chem. Cornmun. (1989) 1383-1385. (235) D. A. Sawyer and B. V. L. Potter, J. Chem. Soc., Perkin Trans. Z(1992) 923-932. (236) C. E. Dreef, J.-P. Jansze, C. J. E. Elie, G. A. van der Marel, and J. H. van Boom, Carbohydr. Res., 234 (1992) 37-50. (237) C. J. J. Elie, R. Verduyn, C. E. Dreef, D. M. Brounts, G. A. van der Marel, and J. H. van Boom, Tetrahedron, 46 (1990) 8243-8254. (238) J. Gigg, R. Gigg, S. Payne, and R. Conant,J. Chem. Soc., Perkin Trans. Z(1987) 423-429. (239) J. Gigg, R. Gigg, S. Payne, and R. Conant, J. Chem. SOC.,Perkin Tram. Z(1987) 17571762. (240) A. P. Kozikowski, G. Powis, A. H. Fauq, W. Tuckmantel, and A. Gallegos, J. Org. Chem., 59 (1994) 963-971. (241) D. Lampe, S. J. Mills, and B. V. L. Potter, J. Chem. Soc., Perkin Trans. I(1992) 28992906. (242) J. F. Marecek and G. D. Prestwich, Tetrahedron Len., 32 (1991) 1863-1866. (243) K. K. Reddy, J. R. Falck, and J. Capdevila, Tetrahedron Lett., 34 (1993) 7869-7872. (244) N. Schnetz-Boutand, B. Spiess, and G. Schlewer, Curbohydr. Res., 259 (1994) 135-140. (245) A. P. Kozikowski, J. J. Kiddle, T. Frew, M. Berggren, and G. Powis, J. Med. Chem., 38 (1995) 1053-1056. (246) A. Zapata, R. F. de la Pradilla, M. Martin-Lomas, and S. PenadBs, J. Org. Chem., 56 (1991) 444-447. (247) I. lzquierdo Cubero, M. T. Plaza Lopez-Espinosa, and P. L. Tornel Osorio, An. Quim., 84 (1988) 340-343. (248) S.-H. Chen and S. J. Danishefsky, Tetrahedron Lett., 31 (1990) 2229-2232. (249) M. Yoshikawa, Y. Yokokawa, Y. Inoue, S. Yamaguchi, N. Murakami, and I. Kitagawa, Tetrahedron, 50 (1994) 9961-9974.

140

T. BRUCE GRINDLEY

(250) H. Boshagen, F.-R. Heiker, and A. M. Schiiller, Carbohydr. Res., 164 (1987) 141-148. (251) S. Hanessian, J. W. Pan, A. Carnell, H. Bouchard, and L. Lesage, J. Org. Chem., 62 (1997) 465-473. (252) F.4. Auzanneau, D. Charon, L. Szabo, and C. Merienne, Carbohydr. Rex, 179 (1988) 125-136. (253) FA. Auzanneau, D. Charon, L. Szilagyi, and L. Szabo, J. Chem. Soc., Perkin Trans. I (1991) 803-809. (254) G . J. P. H. Boons, F. L. Van Delft, P. A. M. van der Klein, G. A. van der Marel, and J. H. van Boom, Tetrahedron, 48 (1992) 885-904. (255) H. Paulsen and E. C. Hoffgen, Tetrahedron Lett., 32 (1991) 2747-2750. (256) M. E. Schwartz, R. R. Breaker, G. T. Asteriadis, J. S. deBear, and G. R. Gough, Bioorg. Med. Chem. Lett., 2 (1992) 1019-1024. (257) G. R. Gough, T. J. Miller, and N. A. Mantick, Tetrahedron Lett., 37 (1996) 981-982. (258) N. Ikota, Chem. Pharm. Bull., 37 (1989) 3399-3402. (259) S. J. Danishefsky and J. Y. Lee, J. Am. Chem. Soc., 111 (1989) 4829-4837. (260) K. Kiyoshima, M. Sakamoto, T. Ishikura, Y. Fukagawa, T. Yoshioka, H. Naganawa, T. Sawa, and T. Takeuchi, Chem. Pharm. Bull., 37 (1989) 861-865. (261) S. Nishiyama, S. Yamamura, K. Hasegawa, M. Sakoda, and K. Harada, Tetrahedron Lett., 32 (1991) 6753-6756. (262) H. Paulsen and C. Krogmann, Liebigs Ann. Chem. (1989) 1203-1213. (263) T. Ogawa, T. Nukada, and M. Matsui, Carbohydr. Res., 101 (1982) 263-270. (264) K.4. Sato, A. Yoshitomo, and Y. Takai, Bull. Chem. Soc. Jpn., 70 (1997) 885-890. (265) C. Liu, S. R. Nahorski, and B. V. L. Potter, Carbohydr. Res., 234 (1992) 107-115. (266) R. S. Coleman and J. R. Fraser, J. Org. Chem., 58 (1993) 385-392. (267) J.-M. Beau, G. Jaurand, J. Esnault, and P. Sinay, Tetrahedron Lett., 28 (1987) 1105-1 108. (268) D. P. Getman, G. A. DeCrescenzo, and R. M. Heintz, Tetrahedron Lett., 32 (1991) 56915692. (269) C. Monneret, R. Gagnet, and J.-C. Florent, J. Carbohydr. Chem., 6 (1987) 221-229. (270) J. S. Brimacombe and K. M. M. Rahman, J. Chem. Soc., ferkin Trans. I(1985) 10671069. (271) C. Monneret, R. Gagnet, and J.-C. Florent, Carbohydr. Rex, 240 (1993) 313-322. (272) L. Chahoua, M. Baltas, L. Gorrichon, P. Tisnts, and C. Zedde, J. Org. Chem., 57 (1992) 5798-5801. (273) P. Jutten, J. Dornhagen, and H.-D. Scharf, Tetrahedron, 43 (1987) 4133-4140. (274) F. Animati, F. Arcamone, M. Berettoni, A. Cipollone, M. Franciotti, and P. Lombardi, J. Chem. Soc., ferkin Trans. I(1996) 1327-1329. (275) J. Yoshimura, A. Aqeel, N. Hong, K.4. Sato, and H. Hashimoto, Carbohydr. Res., 155 (1986) 236-246. (276) S. Hanessian and R. Roy, Can. J. Chem., 63 (1985) 163-172. (277) E. A. Mash and S. K. Nimkar, Tetrahedron Lett., 34 (1993) 385-388. (278) A. Wei and Y. Kishi, J. Org. Chem., 59 (1994) 88-96. (279) J. R. Falck and A. Abdali, Bioorg. Med. Chem. Lett., 3 (1993) 717-720. (280) W. K. Anderson, R. A. Coburn, A. Gopalsamy, and T. J. Howe, Tetrahedron Lett., 31 (1990) 169-170. (281) R. H. Furneaux, G. J. Gainsford, J. M. Mason, and P. C. Tyler, Tetrahedron, 50 (1994) 2131-2160. (282) R. H . Furneaux, J. M. Mason, and P. C. Tyler, Tetrahedron Lett., 35 (1994) 3134-3146. (283) H. Hashimoto, K. Araki, Y. Saito, M. Kawa, and J. Yoshimura, Bull. Chem. Soc. Jpn., 59 (1986) 3131-3136. (284) S. Rio, J.-M. Beau, and J.-C. Jacquinet, Carbohydr. Rex, 219 (1991) 71-90.

APPLICATIONS O F TIN-CONTAINING INTERMEDIATES

141

(285) A. K. Sarkar and J. D. Esko, Carbohydr. Res., 279 (1995) 161-171. (286) H. B. Mereyala and V. R. Kulkarni, Carbohydr. Res., 187 (1989) 154-158. (287) J . Prandi and J.-M. Beau, Tetrahedron Lett., 30 (1989) 4517-4520. (288) J . Pan, 1. Hanna, and J.-Y. Lallemand, Bull. Soc. Chim. Fr., 131 (1994) 665-673. (289) M. W. Bredenkamp, C. W. Holzapfel, and F. Toerien, Synth. Commun., 22 (1992) 24592477. (290) E. Da Silva, J. Prandi, and J.-M. Beau,J. Chem. Soc., Chem. Commun. (1994) 2127-2128. (291) S. Czernecki, C. Leteux, and A. Veyribres, Tetrahedron Lett., 33 (1992) 221-224. (292) T. K. Park, J. M. Peterson, and S. J. Danishefsky, Tetrahedron Lett., 35 (1994) 2671-2674. (293) A. J. Blacker, R. J. Booth, G. M. Davies, and J. K. Sutherland, J. Chem. Soc., Perkin Trans. I (1995) 2861-2870. (294) J. R. Marino-Albernas, R. Bittman, A. Peters, and E. Mayhew, J. Med. Chem., 39 (1996) 3241-3247. (295) F. Bauer, K.-P. Ruess, and M. Lieflander, Liebigs Ann. Chem., (1991) 765-768. (296) T. Ogawa and T. Horisaki, Carbohydr. Res., 123 (1983) Cl-C4. (297) J. A. Marco, M. Carda, F. Gonzalez, S. Rodriguez, and J. Murga, Liebigs Ann. Chem. (1996) 1801-1 810. (298) F. Carreaux, A. DurCault, and J. C. Depezay, Synlett (1992) 527-529. (299) A. Dureault, M. Portal, and J. C. Depezay, Synlett (1991) 225-226. (300) N. Machinaga and C. Kibayashi, Synthesis (1992) 989-994. (301) J. Fitremann, A. DurCault, and J. C. Depezay, Tetrahedron, 51 (1995) 9581-9594. (302) M. Marzi and D. M , Tetrahedron Lett., 30 (1989) 6075-6076. (303) R. J. Maguire and E. J. Thomas, J. Chem. Soc., Perkin Trans. I (1995) 2477-2485. (304) J. L. Marco-Contelles, C. Fernindez, N. Martin-Lebn, and B. Fraser-Reid, Synlett (1990) 167-168. (305) M. H. Kim, J. W. Yang, B. J. Lee, H. 0. Kim, and M. W. Chun, Soul Taehakkyo Yakhak Nonmunjip, I 1 (1986) 71-73. (306) S. Knapp and S. R. Nandan. J. Org. Chem., 59 (1994) 281-283. (307) N. Chida, J. Takeoka, N. Tsutsumi, and S. Ogawa. J. Chem. Soc., Chem. Commun. (1995) 793-794. (308) A. B. Reitz and E. W. Baxter, Tetrahedron Lett., 31 (1990) 6777-6780. (309) J. Thiem and H.-P. Wessel. Liebigs Ann. Chem., (1983) 2173-2184. (310) (3.4.Boons, J. A. Clase, I. C. Lemon, S. V. Ley, and J. Staunton, Tetrahedron, 51 (1995) 5417-5446. (31 1) F.4. Auzanneau, D. Charon, and L. Szab6.J. Chem. Soc., Perkin Trans. Z(1991) 509-517. (312) R. Pontikis and C. Monneret, Nucleosides Nucleotides, 12 (1993) 547-558. (313) M. Carda, P. Casabo. F. Gonzalez, S. Rodriguez, L. R. Domingo, and J. A. Marco, Tetrahedron-Asymmetry, 8 (1997) 559-571. (314) A. Veyrikres, J. Chem. Soc., Perkin Trans. I (1981) 1626-1629. (315) A. Toepfer and R. R. Schmidt, J. Carbohydr. Chem., 12 (1993) 809-822. (316) P. Szab6, J. Chem. Soc., Perkin Trans. I(1989) 919-924. (317) T. Ogawa, T. Kitajima, and T. Nukada, Carbohydr. Res., 123 (1983) C5-C7. (318) S. Knapp, C. Jaramillo. and B. Freeman, J. Org. Chem., 59 (1994) 4800-4804. (319) J. T. Randolph and S. J. Danishefsky, J. Am. Chem. Soc., 117 (1995) 5693-5700. (320) M. A. Nashed, R. I. El-Sokkary, and L. Rateb, Carbohydr. Res., 131 (1984) 47-52. (321) K. Fujita, K. Ohta, K. Masunari, K.-I. Obe. and H. Yamamura. Tetrahedron Lett., 33 (1992) 5519-5520. (322) I. R. Vlahov, P. 1. Vlahova, and R. J. Linhardt, J. Carbohydr. Chem., 16 (1997) 1-10. (323) V. Pedretti. J.-M. Mallet, and P. Sinay, Carbohydr. Res., 244 (1993) 247-257.

142

T. BRUCE GRINDLEY

(324) A. Ricci, S. Roelens, and A. Vannucchi, J. Chem. Soc., Chem. Commun., (1985) 14571458. (325) A. Dessinges, A. Olesker, G. Lukacs, and T. T. Thang, Carbohydr. Res., 126 (1984) C6-C8. (326) T.-L. Su, R. S. Klein, and J. J. Fox, J. Org. Chem., 47 (1982) 1506-1509. (327) G. Hodosi and P. KovfiE, Carbohydr. Rex 303 (1997) 239-243. (328) T. Ogawa, K. Beppu, and S. Nakabayashi, Carbohydr. Res., 93 (1981) C6-C9. (329) T. Ogawa and M. Matsui, Carbohydr. Rex, 51 (1976) C13-Cl8. (330) T. Ogawa, K. Katano, K. Sasajirna, and M. Matsui, Tetrahedron, 37 (1981) 2779-2786. (331) T. Ogawa and S. Nakabayashi, Curbohydr. Res., 97 (1981) 81-86. (332) T. Ogawa, S. Nakabayashi, and K. Sasajima, Carbohydr. Res., 95 (1981) 308-312. (333) T. Ogawa and M. Matsui, Curbohydr. Rex, 86 (1977) C17-C21. (334) M. Gerz, H. Matter, and H. Kessler, Angew. Chem. Int. Ed. Engl., 32 (1993) 269-271. (335) F. Clerici, M. L. Gelmi, and S. Mottadelli,J. Chem. Soc., Perkin Trans. I (1994) 985-988. (336) T. Sato, Y. Fujita, J. Otera, and H. Nozaki, Tetrahedron Lett., 33 (1992) 239-242. (337) R. R. Schmidt, Angew. Chem. Int. Ed. Engl., 25 (1986) 212-235. (338) R. R. Schmidt, Pure Appl. Chem., 61 (1989) 1251-1270. (339) K. Vogel, J. Serling, Y.Herzig, and A. Nudelman, Tetrahedron, 52 (1996) 3049-3056. (340) A. Nudelman, J. Herzig, H. E. Gottlieb, E . Kerinan, and J. Sterling, Curbohydr. Res., 162 (1987) 145-152. (341) M. K. Gurjar and U. K. Saha, Tetrahedron, 48 (1992) 4039-4044. (342) E. Keinan, M. Sahai, Z. Roth, A. Nudelman, and J. Herzig, J. Org. Chem., 50 (1985) 3558-3566. (343) K. K.-C. Liu and S. J. Danishefsky, J. Am. Chem. Soc., 115 (1993) 4933-4934. (344) K. K.-C. Liu and S. J. Danishefsky, J. Org. Chem., 59 (1994) 1895-1897. (345) S. J. Danishefsky, K. Koseki, D. A. Griffith, J. Gervay, J. M. Peterson, F. E. McDonald, and T. Oriyama, J. Am. Chem. Soc., 114 (1992) 8331-8333. (346) S. J. Danishefsky and M. T. Bilodeau, Angew. Chem., Int. Ed., 35 (1996) 1380-1419. (347) C. AugC and A. Veyrihes, J. Chem. Soc., Perkin Trans. I(1979) 1825-1832. (348) C. Cruzado, M. Bernabe, and M. Martin-Lomas, Curbohydr. Res., 203 (1990) 296-301. (349) P. J. Garegg, J.-L. Maloisel, and S. Oscarson, Synthesis (1995) 409-414. (350) M. W. Bredenkamp, C. W. Holzapfel, and A. D. Swanepoel, Tetrahedron Lett., 31 (1990) 2759-2762. (351) T. B. Grindley and R. Ponnampalam, Can. J. Chem., 58 (1980) 1365-1371. (352) V. Bflik, L. Petrus, and V. Farkas, Chem. Zvesti, 29 (1975) 690-696. (353) V. Bflik, Chem. Listy, 77 (1983) 496. (354) M. L. Hayes, N. J. Pennings, A. S. Serianni, and R. Barker, J. Am. Chem. Soc., 104 (1983) 6764-6769.

ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL. 53

SYNTHETIC APPLICATIONS OF SELENIUM-CONTAINING SUGARS BY ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI* Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 62690, USA; and Laboratoire de Chimie des Glucides, Universiti Pierre el Marie Curie, F-7S00S, Paris, France 1. Introduction ....................................................... 11. Preparations of Seleno Sugar Derivatives.. ............................... 1. Early Work ..................................................... 2. Nucleophilic Displacement.. ........................................ 3. Opening of 1.2-Anhydro Sugar Derivatives.. ........................... 4. Addition to Protected Glycals ....................................... 111. Application of Seleno Sugars in Synthesis 1. Utilization of Selenoglycosides in Glycosylation Reaction. ................. 2. Organoselenium-Mediated Alkenylation: Synthesis of Unsaturated Sugars. 3. Cyclization-Mediated Reactions: Synthesis of Deoxy Sugars. IV. Conclusion ........................................................ References ........................................................

143 145 145 148 150 154 167 167 180 186 193 195

................................ .... ...............

I. INTRODUCTION Selenium and its compounds are by no means new in organic chemistry. For many years, organoselenium chemistry was regarded as quite specialized and was consequently largely ignored by organicchemists. Over the past decade, however, this situation has changed with the recognition that organoselenium reagents provide convenient tools for organic synthesis. The new wave of selenium-based methodology has provided useful routes for the introduction of alkenic bonds, as well as for performing many other transformations utilized in numerous syntheses of natural products, including alkaloids, antibiotics, steroids, terpenoids, and carbohydrates. In carbohydrate chemistry, the first article' reporting on the introduction of a selenium atom into a sugar derivative was published in this series in 1945. Since then, a number of reports dealing with the synthesis of deoxy and unsaturated sugars through organoselenium intermediates have been published.

*

Deceased October 16, 1997. 143

Copyright 8 1998 by Academic Press. All rights of reproduction in any form reserved.

144

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

Selenium is the chalcogen below sulfur in the periodic table. The general chemistry of seleno sugars resembles that of thio sugars,la and they are named by the same general principles.Ib However, the differences already evident between oxygen and sulfur progress further when sulfur and selenium are compared: Selenium is less basic but more nucleophilic than sulfur, the selenium atom is larger and more polarizable than sulfur, and the carbon-selenium bond is weaker and less polar than the carbon-sulfur bond. The acidity of the proton alpha to the chalcogen increases markedly from oxygen to sulfur to selenium, and selenoxides eliminate several orders of magnitude faster than sulfoxides.Formation of the very stable diselenides may be an important driving force in reactions, and the low polarity of the C-Se bond enhances the utility of free-radical methodology. Consideration of these fundamental factors offers the possibility of applying rational design rather than empirical experimentation in the optimization of synthetic targets. Accordingly, many useful reactions originally developed using sulfur chemistry may be effected more conveniently by using the selenium analogs; this is particularly the case for reactions introducing alkene functionality and for deoxygenation. In other situations, the use of selenium reagents offers totally new methodology for important synthetic targets, as in glycosidic coupling and the construction of carbon-linked sugars. Whereas the importance of sulfur in biomolecules has long been known, the first indication of the natural occurrence of seleno sugars, in the “selenium indicator plant” Astragalus racernosus, was not demonstrated until 1997. Generally, there was little early information on the specificity of selenium reagents3-$ however, the first one used in the synthesis of a seleno sugar (“selenoisotrehalose”),7 in 1917, was hydrogen selenide. Since then, a number of selenium reagents have been used in organic s y n t h e ~ i s . ~ - ~ Among them, the most common ones used in synthetic carbohydrate chemistry are benzyl selenide (PhCH2SeH), benzylselenol (PhCH2SeOH), phenyl selenide (PhSeH) and its salts, diphenyl selenide (PhSeSePh), phenylselenyl chloride (PhSeCl), phenyl selenocyanate (PhSeCN), o-nitrophenyl selenocyanate (SeCN-c6H4No2-o), potassium selenocyanate (KSeCN), selenium dioxide (Se02),N-phenylselenophthalimide(N-PSP), selenourea (MSBT), dimeth[H2NC(Se)NH2],3-methyl-2-selenoxo-1,3-benzothiazole ylaluminum methaneselenolate (CH3)2AlSeCH3,and phenylselenyl trifluoromethanesulfonate. Many of these reagents are now commercially available, and this circumstance should encourage their use. This article collates information on the reactivity of various organoselenium reagents in modern, synthetic carbohydrate chemistry. It illustrates some of the chemical properties that have contributed to the synthesis of

SELENIUM-CONTAINING SUGARS

145

seleno sugars and their application in the synthesis of unsaturated and deoxy sugars. 11. PREPARATIONS OF SELENO SUGARDERIVATIVES

1. Early Work The pioneering work of Wrede and co-w0rkers,7-~~ performed between 1917 and 1925, was rediscovered almost 30 years later by Bonner and RobinsonI4 during a synthetic approach to several selenoglycosides; they used benzeneselenol in a classic Koenigs-Knorr reaction with tetra-0acetyl-a-D-glucopyranosyl bromide (1). Oxidation of the selenoglycoside 3 with either hydrogen peroxide or potassium permanganate gave not the corresponding selenoxide, but exclusively the product (D-glucose) of C-Se bond cleavage, together with diphenyl selenide. Wagner and c~-worker'~-*~ applied the additional methodology of Wrede7-I3 and Bonner and Robinson14 in the preparation of a number of additional 1-seleno-P-D-glycosides.A similar approach, with a deacetylation step, was employed for the preparation of 0,Se bis(g1ycosides) such as 10 from 4-hydroxybenzeneselenol (7), and N-[(4a-D-g~ucopyranosy~se~eno)pheny~]-~-~-g~ucopyranosy~amine from 4arninobenzeneselenol" (8). Wagner and Nuhn" also detailed treatment of the 1-seleno-P-Dglucoside"*'2 with thiophosgene, a reaction which yielded a thiocyanato derivative after reaction with various classes of amine.

Rh R3

Q-se,

P

MeSO

AcO

Br

I R'=OA~.R~=H 4 R' = H I Rz= OAc

SCHEME1 .

ACO Sa-Sb 6a-6b

R' = Y me,4c1,ZAe

146

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

10

SCHEME 2.

Kocourek and co-workersZ4reported an alternative approach to selenoglycosides that starts from 1 and proceeds supposedly by SN2nucleophilic displacement of bromine with potassium selenobenzoate (PhCOSeK) and formation of 14 with inversion of configuration. Treatment of 14 with sodium methoxide produced the sodium salt of 6-O-acetyl-l-seleno-Dglucose (W), a good precursor in the preparation of selenoglycosides and other derivatives. Similarly, the potassium salt of 1-seleno-D-glucose has been prepared through a selenopseudoureido derivative, as reported by Wagner and Nuhn.” These approaches started with the per-0-acetyl-a-D-glucopyranosy1 bromide (1) and per-0-acetyl-a-D-xylopyranosyl bromide (16). Treatment of potassium salts 19 and 20 with sodium borohydride, followed by deacetylation, produced the diselenides 23 and 24 which, on treatment with metallic potassium in methanol, underwent cleavage of the Se-Se bond with formation of potassium salts 25 and 26. Products 19 and 20 are excellent precursors in the synthesis of symmetrical and unsymmetrical sugar selenides 27-32, as reported by Wagner and N ~ h n . ’ ~ It is noteworthy that all of the methods for the synthesis of selenoglycosides mentioned lead preferentially to the formation of the 1,2-trans prod-

Acb

AcO

11

12 R=N=C=S 13 R = NHCSNH~ R‘ = H. Me, Ph

SCHEME 3.

147

SELENIUM-CONTAINING SUGARS

14

15

SCHEME4.

21 R’ = CHSAc 22 R‘ = H

d

2~ R‘ = CWH

25 = C W H 26R1=H

24d=H

SCHEME5.

R!

\

-m ACO

la

R1= CHSAc

20 R1 = H

Acb

27 R1= R z = C W A c , R3= H, R4= OAc IRI =w=c%oAc,rn=OAc,W=H 29 Rc = CHPAC, w = rn= y R4= OAC 30 RI = R = H, W=-, R4 = OAc S1 Rc = R4= H, W = , RS = OAc S2 Rc = rtZ = RS= H, R4 = OAc

SCHEME6.

148

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

CHzOAc

PhSeH

+:A c*

+

AcfllPyridine

Ac

ePh

33 34 SCHEME

7.

ucts, presumably under kinetic control. However, Wagner and Frenze126 found that formation of both anomers of selenoglycosides occurs during opening of the epoxide ring of the Brig1 anhydride 33 with benzeneselenol. The ‘H NMR spectra of 2 and 34 showed that the signals of protons cis to the aglycon are shifted to lower field compared with those of the glycosides and 1-thioglycosides.

2. Nucleophilic Displacement Potassium selenocyanate is the best-known selenium compound used in synthetic carbohydrate chemistry, and it has traditionally been employed for introduction of a selenocyanate group into the sugar moiety through s N 2 nucleophilic displacement of a sulfonyloxy group, as in the conversion 35 436. Depending on the reaction conditions (solvent and temperature), the major product may be, however, (as reported by Van Es and cow o r k e r ~ ) ? ~either - ~ ~ the 3,6-anhydro derivative, an unsaturated sugar,27or the diselenide. In a fully protected system37,s N 2 displacement of the p tolylsulfonyloxy group by benzyl selenolate ion in methanolic sodium methoxide produced methyl 5-(Se-benzyl)-2,3-O-isopropylidene-5-seleno-a-~ribofuranoside (40) in high ~ i e l d . ~ ’ - ~ ~ In a number of reports, Zingaro and c o - ~ o r k e r s ~ ~ described -~’ several transformations in seleno sugars that involved the application of such selenium reagents as selenourea and potassium selenocyanate in this synthesis of diselenides 43,46, and 49. The first approach involves the SN2 displace-

KSCN ____)

EtOH

35

36 SCHEME 8.

149

SELENIUM-CONTAINING SUGARS

2 M e O k ,MeOH

PhCweH MeONa, MeOH

40

37

H ‘cM/a2

38

SCHEME 9.

ment of the p-tolylsulfonyloxy group in 41 by the selenocyanate ion:’ Subsequent comparable to the earlier reports of Van Es and ~o-workers.”~~’ reduction with sodium borohydride gave diselenide 43. Two alternative approaches to this class of compound (6-6’-diselenides) were also reported.36The first proceeded through selenoureido derivative 45, followed by reduction with sodium hydrogensulfite, and led to the formation of 46. The second approach proceeded by use of iodine oxidation and conversion of the product into diselenide 49. Analogously, Daniel and Zingar040-41 prepared diselenides 52 and 53 as convenient precursors for the synthesis of dimethylselenoarsine derivatives 54 and 55, investigated as potential carcinostatic agents against the P388 system (mouse lymphocyticleukemia). prepared by the method Another example of this class of previously employed in the synthesis of 1-seleno-D-galactose,is the synthesis of 2-acetamido-2-deoxy-1-(dimethylarsino)-l-seleno-c~-~-glucopyranoside (59) and a 6-substituted analog 62. Related examples of the application of

SCHEME 10.

150

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

48

49

SCHEME 11

similar ideas have been r e p ~ r t e d . ~ For ~ - ~example, ’ a-D-glycosyl bromides 1 and 4 have been shown43to react with the triethylammonium salt of 5,5-dimethyl-2-seleno-2-thio-1,4,3,2-dioxyphosphorinane (63) to yield two types of product: 64 and 65, and 66 and 67. These results on the glycosylation reaction of thio and selenothio organophosphorous acids led to two valuable transformations. The first is anomerization of the selenoate 68 by heating in boiling xylene. The second is a selenono-selenolo rearrangement of the seleno ester 70 to the selenoate 71. 3. Opening of l,2-Anhydro Sugar Derivatives

The reaction of 3,4,6-tri-0-acetyl-1,2-anhydro-a-~-glucopyranose (72) with the triethylammonium salt of 5,5-dimethyl-2-0x0-seleno-1,3,2dioxaphosphorinane leads to formation of the diselenide 74 and 3,4,6-

50 R1=OAc,RZ=H 51 Rl=H,RZ=OAc

52 R1= OH,RZ-H 53 R1= H,RZ=OH

SCHEME 12.

54 55

SELENIUM-CONTAINING SUGARS

Cl

56

OAc

60

SCHEME13.

63

66 RI=OAc,RZ=H 67 R ~ = H , R Z = O A C SCHEME14.

151

152

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

68

69

SCHEME15.

tri-U-acetyl-D-glucal (75) in quantitative yield. The generalization of the reaction for other, model anhydro sugars constitutes a potential new entry into the unsaturated sugars, as exemplified by the conversion of 76 via 77 into diselenide 78, the 2,3-alkene 79, and the reagent by-product 80. Another class of seleno sugars derivatives is exemplified by the D-glucosyl selenophosphates. These are readily ~ynthesized~~ by the action of dicyclohexylammonium 0,O-di-tert-butylphosphoroselenoate(82) or its thio counterpart 81on glycosyl bromide 1 at low temperature (because of the thermal instability of the synthesized products 83 and 84). 0-dealkylation of derivatives 83 and 84 was effected with boiling toluene for 5 min or by the catalytic influence of trifluoroacetic acid (TFA) in benzene for 24 h at room temperature. It is noteworthy that both the thio compound 83 and the selenophosphate 84 exist only as /3 anomers under the reaction conditions, as well as during the dealkylation reactions.46Michalska’s continuing research on the sugar phosphoroselenoates, thio- and selenophosphates, and diselenides has been published in two review article^.^^,^' Various physicochemical properties of sugar diselenides, circular dichroism such as spectra, have been d i s c u ~ s e d .The ~ ~ *selenophosphorylation ~~ of 2-deoxy sugars and a seleno-selenolo isomerization which proceeds through an intermediate 2-deoxyglycosyl chloride have been p ~ b l i s h e d .Combination ~~ of the SN2 displacement of a p-tolylsulfonyloxy group by PhSe, with cleavage of the epoxide ring and simultaneous removal of the PhSe group, was used by

70

71

SCHEME 16.

SELENIUM-CONTAININGSUGARS

A

c Ac

0

v

.

-

L

72

33

153

+

B

75 74

SCHEME 17.

JoulliC and ~ o - w o r k e r sin~ the ~ * ~synthesis ~ of such muscarine analogs as Disoepiallomuscarine (90) from sulfonate 87 via intermediate 87a, 88, and 89, and the antibiotic turanomycin (94) via the route 89 + 91 + 92 + 93 + 94. The phenylselenyl group has also been found to be an excellent 95 and leaving group during the photolysis of 1-seleno-D-glycopyranosides

-Thp

OMe

+

72

79

I8

SCHEME 18.

80

154

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

CbOAc

85 X-S 86 X e S e

SCHEME19.

97 in the presence of trimethyltin radicals in toluene solutions4 to form Dglycosyl radicals 96 and 98. The radicals generated in these reactions exist

in conformations established by electron-spin In contrast, the 0-glycoside epoxide 99 under comparable reaction conditions gave simply the alkene 100 rather than radical products.

4. Addition to Protected Glycals a. Hydroxy- and Alkoxy-phenylseleny1ation.-The general procedure used for alkoxyphenylselenylation of both acyclic and cyclic vinyl was employed for alkoxyphenylselenylation of 3,4,6-tri-0-benzyl-~-glucal (99).60Since monosaccharide units were employed as the alkoxy groups (Scheme 22), this reaction afforded a new synthetic route to oligosaccharides. The glycal was first treated with an excess of phenylselenyl chloride in acetonitrile, and the protected monosaccharide (A, B, or C) was then added, together with 2,4,6-trimethylpyridine. A mixture of a-manno and p-glum disaccharides (100 and 101) was obtained, the product of antiaddition, tentatively explained as the result of regiospecific opening of an episelenonium ion. In the case of the selected glucal (99) and under the experimental conditions used, generation of the episelenonium ion that allows diaxial ring opening is favored and the a-manno derivative is predominant. The 2’-Se-phenyl-2’-selenodisaccharides (100a-100c) and (101a-101c) thus synthesize were reduced by triphenyltin hydride to give the correspond-

155

SELENIUM-CONTAINING SUGARS

I

I

NaH ,THF

p)IseN.

90

OMe

/

PhSeNs

I

TsO&

OH

-

87

87.

.OM0

&""' /

a"" /

PhSeHS

AH

91

""1

OH

89

Prh

PhCNCHMe

I

94

93

SCHEME20.

ing 2'-deoxy disaccharides (102a-102c) and (103a-103c) in high yields (9095%). Several years later, hydroxyphenylselenylation of 3,4,6-tri-O-benzylmglucal(99) and also D-galactal(lO4) was realized under similar conditions (phenylselenyl chloride in THF, water, and triethylamine).61The observed

156

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

97 X=SePh

98

hv

-

OMe

100

99 SCHEME 21.

stereochemistry of the reaction differed from that reported by Sinay and co-workers!' The isolated product (-65%) resulted from phenylselenylation from the (Y face. The authors did not report whether another isomer was formed (Scheme 23). The resultant 2-deoxy-2-phenylselenoglycopyranoses105 and 106 were oxidized with m-chloroperoxybenzoic acid in methanol.6' A stereospecific ring-contraction (see 109) occurred, affording respectively the aldehydo derivatives 107 and 108 (no yields reported). Following the same line, studies were undertaken attempting to favor trans-diequatorial opening of the intermediate 12-episelenonium ion, a procedure which could afford, after reduction, a selective route to 2-deoxy-/3-glycosides. Preliminary attempts to produce P-linked glycosides from glycals in a one-step procedure by modifying the previously employed conditions (which afforded a-linked glycosides6'), gave uncontrollable a/P mixtures with low efficiency.60The

SELENIUM-CONTAININGSUGARS

99

lOOa R1= SePh,R2 = A (80%) lOOb R1= SePh,R2 = B (69%)

lOOc R1= SePh,R2 = C (61%) 102a R ~ = H , R ~ = A 102b R1=H,R2=B 1 0 2 ~R ~ = H , R ~ = c

157

lOla R1= Seph, R2 = A (5%) lOlb R1= SePh,R2 = B (@A) lOlc R1= SeF'h, R2 = C (8%) 103a R l = H , R 2 = A 103b R 1 = H, R2 = B 103c R1=H,R2=C

SCHEME 22.

trans-diequatorial 2-Se-phenyl-2-seleno-~-glucopyranosides were, however, prepared with high selectivity by a two-step procedure:* In the first step, 2-Se-phenyl-2-seleno-/3-~-glucopyranosyl acetates were obtained by treatment of the protected D-glucal derivatives 99 and Wa with phenylselenyl chloride and silver acetate in a nonpolar solvent (toluene). Good yields (60-80%) and selectivity (P/a = 9/1) were obtained in the presence of benzyl ethers (Scheme 24). Although the results have not been rationalized, dramatic changes in the stereochemical course of this reaction were observed with different protecting groups. The ability of compounds 109 and 109a to function as glycosyl donors has been evaluated.62The choice of solvent was of prime importance to avoid formation of the (Y anomer. For example, reaction of 109 with monosaccharide derivatives B and D in diethyl ether, in the presence of a catalytic

158

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

=E

99 R ~ = o B ~ , R ~ = H

105 R1= OBn, R2 = H (67%)

107 ~

104 R1= H, R2 = OBn

106 R1= H,R2 = OBn (65%)

108 R1= H, R2 = OBr

1O= B ~~2 ,

amount of trimethylsilyl trifluoromethanesulfonate (Me3SiOTf) afforded the @-linkeddisaccharides 110 and 111 in good yield (92%) and selectivity (Pla = 16/1). Reductive removal of the phenylseleno group of 110 and 111by triphenyltin hydride led to the 2’-deoxy-@-~-disaccharides 112 and 113. Although these methodologies were reported several years ago, they have not often been employed to prepare a-to @-linked2-deoxy disaccharides.

b. Preparation of 2’-Deoxy Nuc1eosides.-A methodology similar to the foregoing was evaluated for the synthesis of 2’-Se-phenylselenonucleosides, which may be converted into 2’-deoxy nucleosides.h”@ Furanoid glycal derivatives 115 and 115 were successively treated with phenylselenyl chloride and silylated uracil or thymine in the presence of silver trifluoromethanesulfonate (AgOTf) as activator. The @-nucleoside derivatives 117a,b and 118a,b were obtained in good yield (90%), but they were contaminated by around 10% of the a anomers. Removal of the 2’-phenylseleno group was effected by reaction with tri-n-butyltin hydride, to afford 2’-deoxy

4 mFq

SELENIUM-CONTAINING SUGARS

159

Bn BnJ &

99 R=OBn 99a R = H

110 R=OBn llOa R=H

111 Rl=B,R2=SePh 112 R1= D, R2 = SePh 113 R ~ = B , R ~ = H 11.1 R ~ = D , R ~ = H

SCHEME24.

nucleosides 1l9a,b and l20a,b. Excellent stereoselectivity was obtained in this reaction because the two diastereofaces of the starting “threo” glycals were strongly differentiated by the presence of the two bulky groups on the same side. It is not immediately apparent if such a high diastereoselectivity could be obtained with “eryrhro” furanoid glycals, precursors of natural 2‘-deoxy-ribo-nucleosides,since the bulky group at C-3 is on the a face. An extension of this approach for the synthesis of 2’-deoxyglycopyranosyluracil derivatives was reported by the same group.@ Peracetylated and perbenzylated D-glucal(99,99b), D-galactal(104,104b) and D-arabinal(120, 120b) were employed as starting materials. The stereoselectivity of the reaction was shown to be dependent on the protecting groups present in the glycal, the structure of the starting glycal, the phenylselenyl reagent used, and the solvent. The best results were obtained with perbenzylated glycals in diethyl ether, using phenylselenyl chloride (PhSeC1) as the activating agent in the presence of AgOTf at low temperature. Under these conditions, 2’4e-phenyl-2’selenoglycopyranosyluracil derivatives (121-127) were obtained in 70-85% yield. The stereoselectivity was high (80 :20) and nucleosides of the p-Dgluco (121), p-D-gafacto (123) and a-D-arabino (127) configurations were principally obtained. A rationalization of these results was presented following the one proposed by Horton et aL6’ for NIS-mediated addition of alcohols to glycals.

160

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

115R=Bn,R1=

117a R=Bn, R1=

116 R = Bn, R1= -CH2OBn 117bR=Bn,R1=

118a R = Bn, R1= -CH20Bn, R2 = H 118b R = Bn, R1= -CH20Bn, R2 = CH3

dy

% ,R~=H

119a R = B ~~, 1 =

o,yQ 119b R = Bn, R1=

,R2=CH3

l2Oa R = Bn, R1= -CH20Bn, R2 = H 120b R = Bn, R1= -CH20Bn, R2 = cH3 SCHEME25.

SELENIUM-CONTAININGSUGARS

161

Q R

99 R = B n 75 R = A c

122 R = B n 122b R = A c

125 R = B n 125b R = A c

104 R = B n 104b R = A c

121 R = B n 121b R = A c

123 R=Bn 123b R-Ac

124 R = B n 124b R = Ac

J2 @ 126 R=Bn 126b R=Ac

127 R = B n 127b R = Ac

u = uracil- 1-yl SCHEME26.

The 2’-phenyl-2’-selenoglycopyranosyluracil derivatives obtained by this method were efficiently transformed into the corresponding 2’-deoxy nucleosides by tri-n-butyltin hydride. of double c. Azido-phenylselenylation.-Azido-phenylselenylation bonds is very powerful and versatile reaction because it allows the one-

162

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

step introduction of two functionalities in a m o l e c ~ l e .Moreover, ~ ~ * ~ ~ the regioselectivity can be controlled with unsymmetrical alkenes. When the reaction is initiated by electrophilic phenylselenium species (such as PhSeC1) in the presence of azide ion, Markovnikov adducts are prevalent.66 Anti-Markovnikov addition products can be obtained by treatment of an alkene with sodium azide and diphenyl diselenide in the presence of (diacetoxyiodo)benzeneF7These two methods of azido-phenylselenylation have been applied to diverse protected glycals, affording respectively 2-Sephenyl-2-selenoglycosyl azides or phenyl2-azido-2-deoxy selenoglycosides (Scheme 27). The overall stereochemical outcome is controlled by the conformation of the starting glycal derivative and the reaction conditions.

(i) Preparation of 24e-phenyl-%seknoglycosyl Azides.-Azido-phenylselenylation of tri-0-acetyl-D-glucal (75) with azide ion in the presence of phenylselenyl chloride in a polar solvent is very slow6' because of the withdrawing effect of the acetyl groups and the ionic mechanism proposed by Hassner.& With perbenzylated glycals, the reaction proceeds smoothly, and glycals 99,104, and 128 were efficiently transformed into 2-Se-phenyl-2-selenoglycosy1 a~ides.6'-~~ As solvent, N,N-dimethylformamide (DMF) was found to be superior to dimethyl sulfoxide (Me2SO), the solvent recommended by Hassner.@The addition was stereoselective and gave the trans-addition products, in agreement with a mechanism involving an episelenonium ion or a related bridged intermediate, which subsequently captures azide ion.

W k "Markovnikov"

seph

W k

"Anti-Markovnikov" SCHEME27.

SELENIUM-CONTAININGSUGARS

163

From tri-0-benzyl-D-glucal (W), a mkture of p-D-gluco- (129) and a-Dmanno (130) pyranosyl azides was ~ b t a i n e d .The ~ . ~same ~ regioselectivity, affording 129 and 130 in similar proportions, was observed when N phenylselenophthalimide (N-PSP) was employed instead of PhSeCl in the presence of sodium azide.68The same outcome was observed with the rhamnal derivative 128,which afforded 131 and 132, whereas only isomer 133 was detected in the ‘H NMR spectrum of the product of addition to glycal 104.69

(ii) Preparation of Phenyl Zazido-2deoxy-se1enoglycosides.-Azidophenyl-selenylation of glycal derivatives by reaction with (diacetoxyiodo) benzene and sodium azide in the presence of diphenyl diselenide was r e p ~ r t e d ~by ” ~two ’ different groups in 1993. The results for glycals 75,99, 104, 104b, 128b, and 134 are listed in Table I. Good yields were obtained with peracetylated glycals 75,104b, and 128b, and the reaction was regiospecific,affording phenyl2-azido-2-deoxy-l-selenoglycopyranosides. From 75 and U?b, inseparable mixtures of gluco and manno derivatives (135-136 and 137,138) were obtained. Galactal triacetate 104b afforded exclusively the gulucto derivative 139 in high yield. Interestingly, in every case, only the a anomer was formed.

Blld

99 R1= OBn,R2 = H

129 R1= N3, R2 = R3 = H, R4 SePh

128

130 R1= R4=H, R2 =N3, R3 SePh

104 R1 =H, R2= OBn

Bn

131 R1 =R4=H, R2 =N3, R3 S e P h 132 R1= N3, R2 = R3 = H,R4 S e P h

133 SCHEME 28.

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

164

99 R=Bn 75 R = A c

104 R=Bn 104b R=Ac

134

128b

CHzOR

I

135 R = Ac, R1 =N3, R2 = H 136 R=Ac,Rl=H,R2=Ng

137 R1 =N3, R2 = H 138 R1= H, R2 =N3

139 R = Ac 144 R=Bn

142 R=Bn,R1 = N j , R 2 = H 143 R = Bn, R1= H, R2 = N3

%-bph fiPh CHflAc

ph

I

\

A

dAc

dAc

140

141 SCHEME 29.

These results are in good agreement with a rapid addition of an electrophilic radical7*(generated by oxidation of azide ion in situ) to C-2 of the electron-rich double bond, affording an anomeric radical stabilized in the (Y configuration by the anomeric effect. Further homolytic reaction with diphenyl diselenide affords the a-selenoglycoside. Extension of this methodology to disaccharidic glycals was reported later.'3 In contrast with the earlier results, only the manno configuration was obtained in the addition product and, although the (Y-D anomer was preponderant, some p-Danomer was formed. In all cases, reactions were

165

SELENIUM-CONTAINING SUGARS TABLE I Azido-phenylselenylation of Glycal Derivatives

Glycal 99 99 75 75 104 104b 104b l2Sb 134

Method"

Product(s)

Yield* (YO)

142 + 143' 142 + 143' 135 + 136c 135 + 136' 144 138 138 137 + 1388 140 + 141

4gd 82e 74d 88f

76 87d

92' 66d 26 + 47d

" Method A: PhI(OAc)z, (PhSe)2, CH2C12, rt. Method B: N-PSP. (CH&SiN,, (nBu)4NF, CH2C12,rt. " Calculated on isolated products. ' gluco/manno = 1/1. ,IRef. 71. ' Ref. 69. f Ref. 12. Rgluco/manno = 112.

slower and afforded lower yields (22-45%) as compared to monosaccharidic glycals. Because of the presence of a strong oxidant, these conditions of azidophenylselenylation did not give satisfactory yields when oxidatively cleav-

d R=R~ R=R~ R=R3

R=R~ R=R~ R=R3

SCHEME 30.

13 : 1 6 : 1 6 : 1

R = R1 (22%) R = R2 (45%) R = R3 (33%)

166

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

able protective groups (such as benzyl ethers or benzylidene acetals) were present in the glycal (see Table 1). With glycall34, cleavage of the benzylidene acetal occurred, as indicated by the resulting mixture of 140 (26%) and 141 (47%) after acetylation of the reaction mixture.” Interestingly, azido-phenylselenylation of perbenzylated glycals 99 and 104 was possible, with the same regioselectivity, when N-PSP was employed in the presence of trimethylsilyl azide and tetra-n-butylammonium fluoride in dichloromethane (see Table I).68771From 99, a mixture of phenyl 2azido-2-deoxy-l-seleno-a-~-gluco(142) and munno-pyranosides 143 was obtained in 82% yield.6*As before, from 104 the a-gulucto isomer 144 was obtained as the sole product.” Although the mechanism of this reaction is not yet fully understood, it should be pointed out that only the cy anomers were obtained, as was the case in reactions with (diacetoxyiodo)benzene. It was verified6*that the regio- and stereo-selectivity were the same for these different conditions of azido-phenylselenylation, by deacetylation of 139 followed by benzylation to furnish 144. The compatibilityof this methodology with many protecting groups was further demonstrated with diversely protected D-galactal derivatives (l&a-e).6R974 CH2OR

145a 145b 145c 145d 145e

qH20R

R=H R=Ac R=Bn R = Bu-t-Me 2% R=Allyl

146a 146b 146c 146d 146e

R = H (59%) R = Ac (91%) R = Bn (84%) R = Bu-t-Me $3(66%) R = Ally1 (74%)

148a R = H (68%) 148b R = A c (73%) 148c R=Bn (76%)

147a R = H 147b R=Ac 147c R=Bn SCHEME 31.

SELENIUM-CONTAININGSUGARS

167

When a silyl ether was present (145d), tetra-n-butylammonium fluoride was omitted and the reaction time was longer than with other glycals, and the yield slightly lower. Furthermore, it was verified that the reaction proceeds faster with electron-rich double bonds and, therefore, can be successfully carried out in the presence of an ally1 ether (145e). Less than 3%of product resulting from double azido-phenylselenylation was isolated. Azido-phenylselenylation was also possible in the presence of one unprotected hydroxyl group (145a and 147a). The compatibility with the benzylidene acetal group, which is very sensitive to oxidation and radical reactions, was also d e m ~ n s t r a t e dwith ~ ~ glycal derivatives 147a-c. Azido-phenylselenylation of a furanoid glycal was also possible under these conditions and afforded exclusively the gluco isomer, which was transformed into a 2-azido-2-deoxy glucopyranosyl donor (see p. 170). In conclusion, these phenyl 2-azido-2-deoxy-l-seleno-~-glucopyranosides could serve as, or be transformed (see p. 170) into, glycosyl donors bearing a nonparticipating group at C-2. For complementarity, their transformation into glycosyl donors bearing a participating N-acetyl group at C-2 was realized by reduction of the azido followed by acetylation.68 OF SELENO SUGARS IN SYNTHESIS 111. APPLICATION

1. Utilization of Selenoglycosides in Glycosylation Reaction and Furana. Preparationof Protected 2-Azido-2-deoxy-glucopyranoses oses.-Protected 2-azido-2-deoxy derivatives of galactose and glucose are extensively used for the synthesis of biologically important 2-amino-2deoxy-D-galactose (and glucose)-containing oligosa~charides.~~*~~ Depending on the leaving group and the promoter employed, they can be directed toward either the 1,2-cis-ora 1,2-truns stereo~hemistry,7~ and regeneration of the amino function is possible under mild conditions. A new and very efficient access to this important class of compounds from diversely protected glycals has been disclosed in which azido-phenylselenylation afforded phenyl2-azido-2-deoxyl-selenoglycopyranosidesin which the anomeric hydroxyl group can be regenerated by hydrolysi~?~.~~ Owing to the soft nature of the selenium atom, sop catalysts such as heavy metal salts were employed for hydrolysis. When ethers or acetals were present as protecting groups, hydrolysis was rapid in the presence of mercury trifluoroacetate in wet tetrahydrofuran, and the protected 2-azido2-deoxyglycopyranoseswere obtained in good yield (Table 11). When mercuric acetate was employed, some 1-0-acetyl derivative was also formed. Hydrolysis of the glucolmunno mixture 142 and 143 resulting from azidophenylselenylation of tri-0-benzyl-D-glucal(99) afforded a mixture of 142a

168

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

W2OR

I

I

142 R=Bn, R1 =N3, R2 = H

142a R = Bn, R 1 = N3, R2 = H

143 R = B n , R l = H , R z = N - j

143a R = Bn, R 1 = H ,R2 = N 3

135 R = A c , R l = N 3 , R 2 = H

1351 R = Ac, R 1 = N3, Rz = H

136 R = Ac, R 1 = H,R2 = N3

136a R = Ac, R 1 = H, R 2 = N 3 CHZOR I

CHBR

I

139 R = A c 144 R = Bn

139a R = Ac 144b R = B n

146a R = Bn 146b R = Ac 146e R = Ally1

149a R = B n 149b R = A c 149e R = Ally1

4 148a R = Bn 148b R = A c

150a R = B n 150b R = Ac

SCHEME32.

169

SELENIUM-CONTAINING SUGARS TABLE I1 Preparation of Variously Protected 2-Azido-2-deoxy-glycopyranoses

Entry

Phenyl selenoglycoside

Method

Product

142 + 143 135 + 136 144 139

A'

142a + 143a 13% + 136s 144a 139a 149s 149b 149e l50a 150b

146C

146b 146e 148a 148b

BC A

B A

A A

A A

Yield 93h

90 87 87 87 79 88 82 86

"Method A: (CFKO&Hg (1.5 equiv), THF-H20, 30 min rt. " 142a was isolated in 66% yield by chromatography. 'Method B: NIS ( 5 equiv). THF-H20, 12 h. rt.

and 143a that could be separated by chromatography, and the gfuco derivative 142a was obtained crystalline (66%).Hydrolysis of the gafacfoderivative 144 proceeded smoothly, and 144a was obtained in 87% yield. Under these conditions, hydrolysis of peracetylated derivatives 135,136, and 139 was very slow, presumably because of the electron-withdrawing effect of the acetoxy groups. When N-iodosuccinimide was employed instead of mercury trifluoroacetate, the reaction was complete in 12 h at room temperature and the yield was good (Table 11). The complete stereochemical control obtained for the azido-phenylselenylation in the gafacfo series (139, 144) makes this procedure especially attractive. For convenience, the two steps can be carried out without purification of the intermediate phenyl 2-azido-2-deoxy-1-selenogalactopyranoside, and the resulting phenyl 2-azido-2-deoxy-1-selenogalactopyranoside is obtained in 72% yield from the galactal derivative. The mild conditions of hydrolysis are compatible with many protecting groups currently employed in oligosaccharide synthesis (see Table 11). To obtain this type of D-glucosamine donor in a stereocontrolled manner, another glycal derivative, namely 3-O-benzyl-2-deoxy-5,6-O-isopropylidene-D-arabino-l,4-anhydro-hex-l-enitol(151), was chosen as starting material because it is easily prepared from D-mannose and because the p-face of the double bond is very hindered.'9 As anticipated, azido-phenylselenylation of 151 afforded an alp mixture of phenyl 2-azido-2-deoxy-l-seleno-~glucofuranosides 152 in high yield. In order to obtain the glucosamine equivalent in pyranose form, compound 152 was treated under acidic conditions in the presence of mercury acetate to effect simultaneous cleavage of

170

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

the acetal group and the selenoglycoside. After acetylation, an culp mixture of 153 was obtained in high yield (83%). Selective deacetylation of the anomeric hydroxyl group afforded 154,which could be activated for glycosidic coupling as a trichloroacetimidate. This transformation of protected glycals into 2-azido-2-deoxyglycopyranoses constitutes a new and efficient method for the preparation of these compounds which are important intermediates in oligosaccharide synthesis. This methodology is compatible with a variety of protecting groups, including acetates, acetals, ally1 ethers, benzyl ethers, benzylidene acetals, and silyl ethers. The mild conditions employed would allow extension of this methodology to glycals derived from disaccharides.

b. Selenoglycosides as Glycosyl Donors.-(i) 0-Glycosidation with Selenog1ycosides.-Phenyl selenoglycosides have been introduced as glycosyl donors and acceptors in glycosidation rea~tions,8’-~~ and the most interesting application is the selective activation of one of the two partners. This may be realized in two different ways: by modulating the reactivities of the partners by suitable choice of protecting g r o ~ p s ~ or - ~by ’ using different types of glycosyl donors and acceptors, which can be activated by different promoters. The latter strategy was employed by Mehta and Pinto.80,82 Glycosylation of the methyl glycoside acceptor 157 with phenyl selenoglycosides 155 and 156 in the presence of AgOTf and potassium carbonate afforded the 1,2-truns-linked disaccharides 158 and 159 in good yield. This reaction was extended to other methyl glycosides acceptors, as depicted and as listed in Table 111. It was also established that, under the same conditions, neither the peracetylated nor the benzylated thioglycoside derivatives were activated. Consequently, the “armed” thioglycoside acceptors 160, 161, and 162 were efficiently glycosylated with “disarmed” selenoglycoside donors 155 and 156.

151

152 SCHEME 33.

153 R = h 154 R = H

SELENIUM-CONTAININGSUGARS

CHZOAc

2R*‘

171

a2oR3

AcO A d

yo%

Ac

155 ~ 1 se=ph, ~2 = H

156

R1 R2 160 H SEt 161 SEt H 162 SEt H -0

A dn+Bgo+

+ r ; +g cA

R1 R2 R3 157 H OMe H 163 SePh H Bn

R3 R4

Bn H H Bn

Bn H

CXZOAc

BnO

AcO A

158 ~ 1 y= ~2 = OM^

159 Rl=H,R2=OMe

163 R1= H,R2 = SEt 164 R1= SEt, R2 = H

165 R1= SEt, R2 = H

Bnb

166 SCHEME 34.

As expected, such a selective activation of per ,enzylatec (“armed”) phenyl selenoglycoside 163 was also possible in the presence of the benzylated thioglycoside acceptor 162. In this case, an cr/p mixture (ratio 2.5 : 1) of disaccharide 166 was obtained in excellent yield (Table 111). The fact that phenyl selenoglycosides are rendered unreactive if an organic base such as collidine or 1,1,3,3-tetramethylurea is employed instead

R1

112

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

TABLE Ill Glycosylation With Selenoglycoside Donors ~

Entry

Donor

1

155 156 155 155 156 163

2 3 4 5 6

Acceptor Product Yield (%) 157 157 160 161 162 162

158 159 163 164 165 157

85 84 80

ia 84 90

of potassium carbonate was also exploited. Under these conditions, selective activation of the glycosyl bromide donor 167in the presence of selenoglycoside acceptors 168 and 169 was possible. The corresponding disaccharides 170 and 171 were obtained in -60% yield.

167 X = Br 172 X = O C o C C l 3

169

168

170

171

173

SCHEME35.

SELENIUM-CONTAININGSUGARS

173

The selective activation of glycoside trichloroacetimidates over phenyl selenoglycosideswas also demonstrated by glycosidation of phenyl selenoglycoside acceptors 168 and 169 with glycosyl trichloroacetimidate 172. In the presence of catalytic amounts of triethylsilyl trifluoromethanesulfonate at -78”C, the disaccharide derivatives 170 and 171 were obtained in respectively 84 and 90% yields. The versatility of phenyl selenoglycosides in oligosaccharide synthesis was further illustrated by the synthesis of the trisaccharide 173. Compound 171 was directly employed as a glycosyl donor for the glycosidation of “armed” thioglycoside acceptor 162 in the presence of AgOTf and K2C03. The thioglycoside product 173 could be directly activated by thiophilic promoters for further glycosidation. The use of phenyl selenoglycosides as glycosyl donors in glycosidation reactions was also studied by Zuurmond et a1.81.83Activation was achieved by iodonium ions generated from Niodosuccinimide and a catalytic amount of trifluoromethanesulfonic acid (NIS-TfOH) or iodonium di-sym-collidine perchlorate (IDCP). Glycosidation of several glycoside acceptors 174,175, and 176 with perbenzoylated phenyl selenoglycoside 177 was possible in the presence of NIS-TfOH (Table IV). The expected 1,2-truns-disaccharides 178, 179, 180, and 182 were obtained in moderate to good yields. Selective activation of the selenoglycoside under these conditions was possible in the presence of benzoylated thioglycoside acceptor 181, and the corresponding disaccharide 182 was obtained in 79% yield (Table IV). Glycosylation with perbenzylated “armed” phenyl selenoglycoside 183 of the same glycoside acceptors (174,175,and 176) was efficient and an a/ /3 mixture of disaccharides 184, 185, and 186 was obtained (Table IV). Since a weak thiophilic promotor (IDCP) was employed in this case, glycosylation of “armed” ethyl thioglycoside acceptor 187 was also possible, affording an alp mixture of 188 (Table V). Furthermore, selective activation of differently protected selenoglycosides was also possible with IDCP as promoter. Perbenzylated “armed” phenyl selenoglycoside 183 was selectively activated in the presence of “disarmed” acceptor 189 and an alp mixture of disaccharide 190 was obtained. With the less-reactive secondary hydroxyl group of 191,the yield of 192 was lower. Some disappointing results were reported later by the same group in an attempt to use phenyl selenoglycoside donors for the synthesis of a tetrasaccharide.86No glycosylation was possible with phenyl selenoglycoside 193 in the presence of NIS-TfOH, whereas 40% yield was obtained with the corresponding trichloroacetimidate 194. The previously discussed selective activation methodologies80*81 were also evaluated with phenyl2-0-benzoyl-2,3-di-0-benzyl-l-seleno-~-~-ribofuranoside (195)as the ribofuranosyl donor.87

174

ZBIGNIEW J. WITCZAK A N D STANISLAS CZERNECKI

R20 -0Me \

OR1

L3

H

174R1 = R2=R3 = Bn, R4= H 175R1= H R2=R3= (CMe)z,R4=Tr

176

(OH R10

SePh

181 R-Bz 187 R-Bn

177 R1= R2 = Bz 183 R I = R ~=BII 180 R1 =Bz, R L H

191 SCHEME36.

Glycosylation of ribofuranoside 195 with pyranoside acceptors 197 and 1% in the presence of AgOTf-K2C03 afforded the &linked disaccharides 198 and 199 in 60% yields, but the condensation was accompanied by the formation of the dimer 200 in appreciable amount (Table VI). Attempted

193X = SePh 194R = O C O C C 1 3 SCHEME 37.

175

SELENI UM-CO NTAINING SUGARS

TABLE IV Glyeosidation with Perbenzoylated Phenyl Selenoglycoside 177 Entry

Donor

Acceptor

Disaccharide

Yield (YO)

0

91

BzO

1

177

174

Bzoa

n

O BnO

h

O BnO

M

e

178

2

177

67

175

179

3

177

50

176

180

4

177

181

BzO&T7P

0

19

BzO BzO 182

glycosylation of ribofuranoside derivatives 201-205 was also disappointing. With terminal ethyl P-D-ribofuranoside 201, the formation of dimer 200 was also apparent (Table VI). Selective activation of the phenyl selenoribofuranoside 195 in the presSurprisingly, ’ reacence of 1-thioribofuranoside acceptors was also s t ~ d i e d . ~ tion of 195 with benzylated ethyl 1-thio-P-D-ribofuranoside (202) afforded the product of trans glycosidation, 203 (Table VI). The same phenomenon

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

176

TABLEV Glycosidation with Perbenzylated Phenyl Selenoglycoside 183

Yield (YO) Entry Donor Acceptor

1

183

Disaccharide

(a//.ratio) ?

82 (2%)

175 BnO BnO 184

2

183

176

185

3

183

176

186

Bno BnO

4

183

187

79 (5/1)

BzO

tE&-+fozBonB

BzO 188

BnO BnO

S

5

183

B

z

O 87

189

BzO O 190

t

s BzO

L SePh

(4/1)

SELENIUM-CONTAINING SUGARS

177

TABLE V (Continued) Yield (YO)

Entry Donor Acceptor

6

183

(a@ ratio)

Disaccharide

191

SePh

45 (911)

192

was previously reported with ethyl thioglycosides as acceptor^.^*-^^ When phenyl 1-thio-P-D-ribofuranoside(204) was employed as acceptor, the trunsglycosylation was suppressed, but the yield of disaccharide 208 was low because the dimer 200 was also formed (Table VI). Activation of 195 with iodonium species82did not significantly improve the results. Glycosidation with the weakly thiophilic IDCP gave exclusively (albeit in poor yield) the ortho-ether derivative 210. In the presence of a strong thiophilic promoter (NIS-TfOH), a mixture of 208 and 200 was obtained. Similar results were obtained with the 4-nitrophenyl 1-thioribofuranoside acceptor 205 (Table VI). On account of side reactions, glycosidation with selenoribofuranoside donors is not very efficient under the conditions presently employed87and further work is needed to find better conditions. (ii) Preparation of Seleno-disaccharides.-In recent years, much effort has been devoted to the synthesis of unnatural di- and oligosaccharides in which the bridging oxygen atom of the glycosidic linkage is replaced by a nitr0gen,9'-~' or carbon at0rn,9~.~~ because such compounds could act as glycosidase inhibit01-s~~ and might exhibit interesting biological properties including antidiabetic, anti-inflammatory, and antiviral activities. A versatile methodology for the preparation of a new class of such compounds in which the bridging atom is selenium has been reported.95 To achieve this goal two strategies were evaluated: Method A, condensation of a glycosyl selenoate of known anomeric configuration with a protected deoxyhalo sugar, by analogy with the method employed for the synthesis of thio-disaccharide~~'; and Method B, condensation of a selenosugar derivative with a glycosyl halide. A perbenzylated a-glucopyranosyl selenoate was generated by reduction of the protected diglycosyl diselenide 211. Further reaction with methyl

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

178

X = SePh; R = Bz X=OEt;R=H X=SEt;R=H X = SEt; R = Bz X=SPh;R=H X = SPhN%; R = H

195 201 202 203 204 205

BJ B~

A

196R=H 1 9 8 R = BnO

197R=H

BnO 206 x = O E t 207 X=SEt

-pJ ;;; U

BJ

+h 210

ABZ

SCHEME38.

2,3,4-tri-O-benzyl-6-deoxy-6-iodo-a-~-glucopyranoside~~ (212) afforded the a-seleno-disaccharide213 in 70%yield. The same sequence of reactions was not effective with the peracetylated diglycopyranosyl diselenide.

SELENIUM-CONTAINING SUGARS

179

TABLE VI Glycosidations with Phenyl Selenoribofuranoside 195

Entry

Acceptor

Promoter

1 2 3

1% 197 201 202 204 204 204 205 205

AgOTF-K2CO3

4 5

6 7 8 9

Temp "C 20

0 20 20 20 20 -50

IDCP NIS-TfOH

Yield (YO) 60 56 52 (19) 66 25 (22) 34 20 (8) 39 (40) 55 (30)

Method B was evaluated with the diglucosyl diselenide 216,prepared in two steps by reaction of the 6-deoxy-6-iodo derivative 214 with selenourea and transformation of the pseudourea resulting 215 and 217.The selenoate was generated by reduction of 216 and allowed to react with 2,3,4,6-tetra0-acetyl-a-D-glucopyranosyl bromide in DMF, affording protected disaccharide 217. The free (1 + 6)-P-linked 6-selenodisaccharide 218 was obtained in 70% yield after deacetylation. This methodology could find

Method A:

bMe

Method B:

SCHEME 39.

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

I80

1 2

211

212 R = B n , Y = I 214 R = A c , Y = I 215 R = A c , Y C S e <

mz+,1M Z

CHzOBn

*

:

*

%

R

CHZOR

e

217R=Ac 218R=H SCHEME 40.

application for the synthesis of a variety of selenodisaccharides from other diglycosyl diselenides and other acetylated glycosyl halides.

2. Organoselenium-Mediated Alkenylations: Synthesis of Unsaturated Sugars Reactions leading to the formation of alkenic or a,@-unsaturated bonds are very important in synthesis. This type of functionality is synthetically versatile, and of wide utility in the carbohydrate field. The use of sulfur reagents for conversion of sugar epoxides on vicinal disulfonates into alkenes is well e~tablished~’”.~~”, and subsequent work with selenium reagents provided essentially comparable results. Thus, treatment of methyl 2,3anhydro-4,6-O-benzylidene-a-~-mannopyranoside (219) with potassium selenocyanate in aqueous 2-methoxymethanol afforded methyl 4,6-0benzylidene-2,3-dideoxy-a-~-erythro-hex-2-enopyranoside(22O).” Similarly, treatment of 5,6-anhydro-1,2-O-isopropylidene-a-~-glucofuranose (221) with potassium selenocyanate in methanol at room temperature

181

SELENIUM-CONTAINING SUGARS

OM0

220

219

T-Y

Td+oJ O-CMe2

02

224

223 SCHEME 41.

gave, instead of the expected episelenide, 1,2-O-isopropylidene-5,6dideoxy-a-~-xylo-hex-5-enofuranose (222) in good yield. The same 5enose (222) was formed during the reaction of 1,2-O-isopropylidene-3,6di-0-p-tolylsulfonyl-a-D-glucofuranose (223) in a boiling solution of potassium selenocyanate in N,N-dimethylformamide, along with 3,6anhydro-l,2-0-isopropyl~dene-5-O-p-tolylsulfonyl-a-~-glucofuranose (224) as a c o - p r o d ~ c tFormation .~~ of unsaturated derivatives of acyclic sugars by this methodology has also been reported.” Treatment of 1,2:5,6-di-O-isopropylidene-3,4-di-O-p-tolylsulfonyl-~-mannitol (225) with potassium selenocyanate in refluxing N,N-dimethylformamide gave (E)-1,2:5,6-di-O-isopropylidene-~-fhreo-3-hexene-l,2,5,6-tetrol(226). Similarly,compound 226 was prepared (in better yield) from 3,4-anhydro-1,2:5,6-di-O-isopropylidene-~talitol(227) with potassium selenocyanate in boiling 2-methoxyethanol. Epoxide-ring opening of 5,6-anhydro-1,2:3,4-di-O-isopropylidene-~mannitol (228) occurs under relatively mild conditions with potassium

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

182

225

226

I

7°-cMez ?-OH li$ -SeCN

228

227

-

I

%Me,

I

Hc

d 229

SCHEME 42.

selenocyanate in methanol, leading to 3,4:5,6-di-O-isopropylidene-~arabino-l-he~ene-3,4,5,6-tetrol~~ (229). Paulsen and co-workersg8successfully employed a new organoselenium for conversion of reagent namely, 2-methyl-2-selenoxo-1,3-benzothiazole various anhydro sugars 230-232 and 236 into unsaturated derivatives 233234 and 235. The conversion proceeds during 5 to 10 h at room temperature in generally high yields. Interestingly, during the ring opening of epoxide 236, the formation, albeit in only 4% yield, of diselenide 238 was observed. This possibly occurred through the intermediate 237, which undergoes P-elimination of water and finally dimerization, with the formation of diselenide 238. In the case of formation of compound 235, the reaction probably proceeds by way of episelenide 240, as depicted. It is noteworthy that, under the foregoing reaction conditions, the 1,6-anor 1,6:3,4-dianhydrosugars 241-242 and 245 is unrehydro ring of the 1,6:2,3.-

SELENIUM-CONTAINING SUGARS

-"

183

eo

oh

230 R1 = O , R 2 = H 231 Rl=O,R2=CH3 232 R1= H ,R2 = C&Br

233 @=H 234 R2=CH3

236

I

237

236

232

-

-

1

-SR

-

238

-

1 235

S OH m e

OMe

-

-J

240

239 SCHEME 43.

active, and cleavage of only the 2,3- or 3,4-anhydro ring is observed. This selectivity of the reaction constitutes a new entry to the rare class of unsaturated 1,6-anhydro sugars 243-244 and 246.

a

@-

R

R

243 R = OCHzPh 244 R=N3

241 R = OCHzPh 242 R=N3 SCHEME 44.

in4

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

246

245 SCHEME 45.

Umezawa and c o - ~ o r k e r employed s~~ a similar approach for the stereospecific transformation of a D-sugar unit into an L-sugar in complex aminoglycoside antibiotics. The sequence starts from epoxide 247. Epoxide-ring opening with phenyl selenide (generated, in place, from diphenyl diselenide and sodium borohydride), followed by oxidative elimination of the phenylselenyl group with rn-chloroperoxybenzoic acid (MCPBA), afforded the unsaturated aminoglycoside derivative 252 through intermediates 249251. Sinay and co-workers'm reported a valuable approach to vinyl glycosides involving fragmentation of the corresponding 2-(phenylseleny1)ethyl glycosides generated from 2-(phenylseleny1)ethanol. The synthetic approach starts from glycosyl bromide 1 or 4, or 3,4,6-tri-O-acetyl-~-glucal (75), and proceeds by formation of vinyl glycosides 255, 256, and 258. Thermal rearrangement of 258 leads to the 3-C-substituted glycal259. Another important application of organoselenium reagents in carbohydrate chemistry is formation of unsaturated sugars in reactions employing the N-phenylselenophthalimide (N-PSP)-tributylphosphine system.'"' This approach is exemplified by treatment of an appropriately protected methyl cr-D-glucopyranoside (260) with N-PSP-Bu3P in oxolane solution at O", followed by oxyselenation with H202, with the formation of 262. This transformation allows the formation of an alkene group from a primary alcohol under relatively mild conditions. The N-phenylselenophthalimide (NPSP)-tributylphosphine (Bu3P) system is also a useful reagent for the facile transformation of carboxylic acids into seleno esters, and of alcohols into alkyl phenyl selenides (including some carbohydrate derivatives).'02 The utility of N-phenylselenophthalimide (NPSP) as a selenylating agent has been reviewed by Nicolaou and co-worker~.'"~ Another useful system is o-nitrophenyl selenocyanate and tributylphosphine (Bu3P), developed by Grieco and co-workers,'"-'"6 which has been employed in the synthesis of intermediates leading to the ionophone antibiotic ~alcimycin.'"~ A selenylation-elimination sequence with an ArSeCN-BURPsystem was used in the preparation of the key intermediate 265, from the primary

185

SELENIUM-CONTAINING SUGARS

OR

248

247

-

rNHBoc 1 HNBoc

PhSe

249

%?-r5SGq r

cNHBoc

HO

,NHBoc

1

BocNH OR

OR

252 251

R = BOC = tauocoSCHEME46.

alcohol 263 via the intermediate 264, for the synthesis of sugar portion of antibiotics related to ang~stmycin."~ The Prelog-Djerassi lactone'08 268 has been similarly synthesized'08-'0Yfrom 266 via compound 267. Seleno esters are also produced in good yield by reactions of dimethylaluminim methanoselen~late''~(CH&A1SeCH3, with the protected Cribofuranosyl acetate 269. Treating the selenol ester 270 with either cuprous or mercuric chloride produced the (Gender) lactone."' 271, a product useful in the synthesis of various C-nucleoside antibiotics.' 11~112

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

186

255 256

253 R l = O A c , m = H 184 R1 =H,@=OAc

75 257

I

SCHEME 47.

3. Cyclization-Mediated Reactions: Synthesis of Deoxy Sugars The synthetic versatility of the phenylseleno (PhSe) group is well established in general organic ~ynthesis."~-"*~ Two of the most common and useful transformations of this group are its oxidative and reductive removal, to introduce unsaturation and lead to saturation, respectively. Conceptually, both reactions may involve the intramolecular trapping of a selenium species by a suitably oriented nucleophile, to give different products, depending upon the linking hai in."^-'^^ Kane and Mann"' have applied selenocyclization for the synthesis of Cglycosyl compounds. Treatment of an appropriately protected ribose deriva-

260

261

SCHEME 48.

262

SELENIUM-CONTAININGSUGARS

&

o-NO&R&eCNIBuJP

ws

+? M

Me

Me

187

263

264

265 SCHEME 49.

tive (272) with phenylselenyl chloride gave the P-cyclized product 273 in 40% yield, and subsequent deselenylation with hydrogen peroxide led to the alkene 274. Many other examples of selenocyclization have been reand here only selected reactions are discussed to illustrate the

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

188

coocy

COOCH3

I

I

(CH&AlSeCy

or CuC12

MeOCHzOH 0

0

' cI

'cL2 269

270

82

271

SCHEME 51.

general strategy for utilizing selenium reagents. A related ring-closure approach'20*'21involved stereoselective C-functionalization of the anomeric center of the acyclic precursor 6-O-benzyl-l,2-dideoxy-3,4-o-isopropylidene-D-ribo-hex-1-enitol (275) with the formation of the C-glycosyl product 276. a. Radical Cyc1ization.-Stereoselective C-C bond-formation at the anomeric position of a cyclic sugar, based on an intramolecular radical cyclization or migration reaction, has been rep~rted.'~'-'~'. This particularly convenient approach offers the following advantages in the comparison with the intermolecular processes: first a more efficient C-C bond formation: second, much higher stereoselectivity because of favored formation of a cis ring junction; and third, ready access to both a- and p-C-glycosyl products. However, the approach developed by DeMesmaeker and co-workers,'44starting with compound 277, unexpectedly gave a product having the L-ido configuration (280). This result may be explained by an intramolecular hydrogen-atom transfer of H-5 to the C-lcentered radical by Bu3SnH, either from the p-face leading to the L-ido compound 280 or from the a face to give compound 279 (in 22% yield).

272

273

SCHEME 52.

214

SELENIUM-CONTAININGSUGARS

189

WCH cH2

I1

0

0

PhSeCl

Na H C 4

‘CL,

276

275 SCHEME 53.

These authors also demonstrated that the p-C-glycosyl compounds 283 and 284 could be obtained from the corresponding manno precursor. The configuration at the anomeric center is /3 because of the geometric requirement for cis ring fusion. In another example of the selenide radical cyclization,’uathe benzylidene derivative 286 cyclized to 287 and 288 under photolysis conditions. However, no hydrogen atom migration was observed in this case. The stereo-

QCb 280

279

281

282

SCHEME 54.

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

190

hPh 283

285

284

SCHEME 55.

selectivity increases in favor of the depicted epimer 287, formed in 79% yield. Further examples of radical cy~lization'~~ involve the formation of functionalized heterocycles 290 and 292 from precursors 289 and 291, respectively. The high efficiency of the radical cyclization reaction with the formation of two heterocycles in high yield is noteworthy. All of the radical cyclization reactions mediated by Bu3SnH proceed stereospecifically through intramolecular hydrogen abstraction and are performed at a low concentration of the reducing agent. The formation of products of simple reduction of the phenylselenyl group has not yet been observed under such reaction conditions. However, reduction of acetylated or benzoylated glucosyl selenides with a low concentration of Bu3SnH leads to 2-deoxy sugars.141-143 This particular approach proceeds by an important step in this radical-chain reaction, namely, the &-selective 12-migration of an ester group to the anomeric position, yielding the observed Q anomer in excellent (92%) yield. The reductive elimination reaction of selenides can also be applied to furanosides. These approaches may be regarded as a true general synthetic methodology for the preparation of 2-deoxy sugars.

f

phq*s...

PhMe. hv -700 C

286

/

-nB

287

U**Ic&

R

288

SCHEME 56.

-w

SELENIUM-CONTAINING SUGARS

191

BEts, B@nH, I min. RT.*

Bn

m, 290

289

SCHEME 51.

b. Seleno1actonization.-Benzeneselenyl triflate is highly electrophilic and induces electrophilic-mediated cyclization of a#-unsaturated carboxylic acids with the formation of lactones.'@' The previously mentioned phenylselenyl chloride-mediated cyclization of unsaturated sugars, developed by Nicolaou and c o - ~ o r k e r s ~and ~ * ~commonly ~"~ termed phenylselenolactonization, has also been employed in the synthesis of butenolides as illustrated in the conversion of alkenes 297a-c into lactones 299a-c via adducts

294

AlBN

Bzo

BZO

OBZ

295

296 SCHEME 58.

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

192

PhSeCI CH&

-7WC R

SePh

R

R=Me,Et,Ph

298ac

299a-c

297a-c SCHEME 59.

298a-c. The phenylselenolactonization reaction proceeds with regio- or ring selectivity. For example, 5-membered ring lactones are usually formed preferably over four- or six-membered rings as reported by Liotta and coworkers, (such as 302, formed from 300 via 301).15' These two examples constitute a general strategy for the synthesis of unsaturated lactones. Ley and c o - w o r k e r ~have ' ~ ~ successfully employed the phenylselenoetherification reaction for the synthesis of 1,3-disubstituted tetrahydropyrans 305a,b, starting from enolic hydroxy precursors 303a,b via intermediate 300a,b. c. Tethered Approach Connection.-This temporary connection approach was developed by Stork,154using a phenylthio activating group. This type of synthetic approach to connect two sugar units has tremendous synthetic value, and thus far has been the only stereoselective route to specific carba-disaccharides. Sina)i and c o - w o r k e r ~ ' used ~ ~ - this ~ ~ ~strategy, extending it to the phenylselenyl group in the synthesis of the such 4-carba gluco disaccharides as 310 from precursors 306 and 307, via intermediates 308 and 309. The highly observed selectivity is not a general approach; thus, two isomeric products result from such cyclization when the dimethylsilyl tether is between 0-2 and 0-3. An alternative a p p r ~ a c h ,which ' ~ ~ utilizes a ketal function as a temporary tether, involves treatment of orthoester 311 with benzenselenol and mercuric bromide with the formation of the anomeric selenide 312. Derivatization of the acetate 312 with Tebbe's refollowed by coupling with agent [(~yclopentadienyl)~TiCH~-(Cl)AlMe~],

bOH

I

SePh

300

301 SCHEME 60.

302

SELENIUM-CONTAINING SUGARS

193

R = Me, ChPh

3034 b

305a.b

304a, b

SCHEME 61.

alkene 314, produces the ketal315, which, upon successive reduction with tributyltin hydride to 316 and deprotection, gives the C-(1 -+ 4)-disaccharide 317. A small proportion of the C-manno isomer was detected in the reaction mixture. IV. CONCLUSION

The synthesis and application of selenium intermediates and seleno sugars, and the subsequent study of their transformation into various classes of useful precursors and target derivatives, are witnessing rapid new development. This new field of synthetic carbohydrate chemistry offers new methodologies for general organic and natural-product syntheses, and new cyoBn

n4uU BnO

W

lmidazole

306

308 BnO OMe

307

AIBN

GY

I

HF

-.. --

CH. OH

310

B y SnH

OMS

H

o

V

M

.

309

SCHEME 62.

6Me

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

194

PhSeHMgBrz MeCN

Bn

/

Me

311

312

Tebbe naaent

Bn

314 4 A dews

Bn Bu$nH

AlBN Bn

315

Me 316

317

We

SCHEME63.

selenium analogs with potential biological activity. The multiplicity of methods for functionalizing selenium intermediates provides a number of attractive approaches to various classes of interesting compounds previously unattainable by conventional methods. From the biological point of view, the synthesis and characterization of S- and Se-containing analogs of biomolecules has attracted considerable interest, focused especially on chalcogen derivatives of amino acids, proteins, purines, and pyrimidines. Although the importance of sulfur in biomolecules has long been known, the essential

SELENIUM-CONTAINING SUGARS

195

requirement of selenium for mammalian organisms has not yet been explored. Moreover, the discovery of a Se-dependent enzyme, glutathione p e r oxida~e ?~.~ has again demonstrated the essential role of selenium and its difference from sulfur. Similarly, selenocysteine is now recognized as a genuine biological amino acid with its own t-RNA and DNA codon, stimulating new areas of biomedical research. These two important discoveries, with implications for the biological activity of new derivatives of selenium, should ensure that this rapidly developing field of synthetic carbohydrate chemistry remains a rich area of investigation for many years to come. REFERENCES (1) A. L. Raymond, Adv. Carbohydr. Chem., 1 (1945) 129-145. ( l a ) D. Horton and D. H. Hutson, Adv. Carbohydr. Chem., 18 (1963) 123-199. (lb) IUPAC-IUBMB Nomenclature of Carbohydrates, Adv. Carbohydr. Chem. Biochem., 52 (1997) 43-171, 2-Carb-15. (2) R. A. Zingaro, J. Price, and C. R. Benedict, J. Carbohydr. Nucleos. Nucleof., 4 (1977) 271-292. (3) Information on earlier and modern organoselenium chemistry maybe found in: (a) Houben-Weyl, Methoden der Organischen Chemie, Vol. 9, George Thieme Verlag, Stuttgart, 1955, p. 917; (b) R. A. Zingaro and W. C. Cooper (Eds.), Selenium, Van Nostrand-Reinhold, New York, 1974; (c) D. L. Klayman and H. H. Gunther (Eds.), Organic Selenium Compounds; Their Chemistry and Biology, Wiley, New York, 1972; (d) D. L. J. Clive, Tetrahedron, 34 (1978) 22-30; (e) Z. J. Witczak and R. L. Whistler, Heterocycles, 19 (1982) 1719-1734; (f) Z. J. Witczak, Nucleos. Nucleot., 2 (1983) 295-318; (g) S. V. Ley, Chem. Ind. (London), (1985) 101-106, (h) D. Liotta and R. Monahan, 111, Science, 231 (1986) 356-361; (i) S. Patai and Z. Rappoport (Eds.), The Chemistry of Organic Selenium and Tellurium Compounds, Vol. 1, Wiley, New York, 1986; 0‘) C. Paulmier, Selenium Reagents and Intermediates in Organic Synthesis, Pergamon, Oxford, New York, 1986. (4) K. C. Nicolaou and N. A. Petasis, Selenium in Natural Product Synthesis, CIS Inc. Philadelphia, 1984. (5) E. H. Ganther, in Ref. 3b, pp. 609-611. (6) R. A. Zingaro, Chem. Scr., 8A (1975) 793-804. (7) W. Schneider and F. Wrede, Ber., 50 (1917) 793-804. (8) F. Wrede, Hoppe-Seyler’s 2. Physiol. Chem., 112 (1921) 1-12. (9) F. Wrede, Biochem. Z., 83 (1917) 96-109. (10) F. Wrede, Ber., 52 (1919) 2135-2149. (11) W. Schneider and A. Beuther, Ber., 52 (1919) 2135-2149. (12) F. Wrede, Hoppe-Seyler’s 2. Physiol. Chem., 115 (1921) 284-304. (13) F. Wrede and W. Zimmermann, Hoppe-Seyler’s Z. Physiol. Chem., 148 (1925) 65-68. (14) W. A. Bonner and A. Robinson, J. Am. Chem. SOC.,72 (1950) 354-356. (15) G. Wagner and G. Lehmann, Pharm. Zentralhalle, 100 (1961) 160-169. (16) G. Wagner, E. Fickweiler, P. Nuhn, and H. Pischel, 2. Chem., 3 (1963) 62-64. (17) G. Wagner and P. Nuhn, 2. Chem., 3 (1963) 64-65. (18) G. Wagner and P. Nuhn, Arch. Pharm. (Weinheim, Ger.), 296 (1963) 374-383. (19) G. Wagner and P. Nuhn, Arch. Pharm. (Weinheim, Ger.), 297 (1964) 81-88. (20) G. Wagner and P. Nuhn, Arch. Pharm. (Weinheim, Ger.), 298 (1965) 686-692.

196

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

(21) G. Wagner and P. Nuhn, Arch. Phurm. (Weinheim, Ger.),298 (1965) 692-695. (22) G. Wagner and P. Nuhn, Phurm. Zentrulhulle, 104 (1965) 328-333. (23) G. Wagner and P. Nuhn, fhurmuzie, 22 (1967), 548-553. (24) J. Kocourek, J. Klenha, and V. Jiravek, Chem. Ind. (London) (1963) 1397-1398. (25) G. Wagner and P. Nuhn, Arch. Phurm. (Weinheim, Ger.) 297 (1964) 461-473. (26) H. Frenzel, P. Nuhn, and G.Wagner,Arch. Phurm. (Weinheim, Ger.),302 (1962) 62-72. (27) T. Van Es, Curbohydr. Res., 5 (1967) 282-285. (28) T. Van Es and R. L. Whistler, Tetrahedron, 23 (1971) 2849-2853. (29) T. Van Es and J. J. Rabelo, Curbohydr. Res., 29 (1973) 252-254. (30) J. J. Rabelo and T. Van Es, Carbohydr. Res., 30 (1973) 202-204. (31) J. J. Rabelo and T. Van Es, Curbohydr. Rex, 30 (1973) 381-385. . and T. Van Es, Curbohydr. Res., 32 (1974) 175-179. (32) J. .IRabelo (33) T. Van Es and J. J. Rabelo, Curbohydr. Res., 36 (1974) 408-411. (34) K. Blumberg, A. Fuccello, and T. Van Es, Curbohydr. Res., 59 (1977) 351-362. (35) R. A. Zingaro and J. K. Thompson, Curbohydr. Rex, 29 (1973) 147-152. (36) C. D. Mickey, P. H. Javora, and R. A. Zingaro, J. Curbohydr. Nucleos. Nucleot., 1 (1974) 291-298. (37) C. L. Bairnbridge, C. D. Mickey, and R. A. Zingaro, J . Chem. SOC., Perkin Trans. I (1975) 1395-1397. (38) G. C. Chen, R. A. Zingaro, and C. R. Thompson, Curbohydr. Res., 39 (1975) 61-66. (39) G. C. Chen, J. R. Daniel, and R. A. Zingaro, Curbohydr. Res., 50 (1976) 53-62. (40) J. R. Daniel and R. A. Zingaro, Curbohydr. Res., 64 (1978) 69-79. (41) J. R.Daniel and R. A. Zingaro, Phosphorus Sulfur, 4 (1978) 179-185. (42) G. C. Chen, C. H. Banks, K. J. Irgolic, and R. A. Zingaro, J. Chem. SOC., Perkin Truns. 1, (1980) 2287-2293. (43) M. Michalska, J. Michalski, and I. Orlich-Krezel, Tetrahedron, 34 (1978) 7821-2824. (44)M. Michalska, J. Michalski, and I. Orlich-Krezel, Pol. J. Chem., 53 (1979) 253-264. (45) W. Kudelska and M. Michalska, Tetrahedron, 37 (1981) 2994-2998. (46) P. Lipka and M. Michalska, Curbohydr. Rex, 113 (1983) 317-320. (47) M. Michalska and J. Michalski, Heterocycles, 28 (1989) 1249-1256. (48) M. Michalska, Biouct. MoL, 1987(Biophosphates and Their Analogues) 211-222; Chem. Absrr., 108, (1988) 221-502. (49) M. Michalska and G. Snatzke, Lieb. Ann. Chem., (1987) 179-181. (50) G. Snatzke in S. Patai and Z. Rappoport (Eds.), The Chemistry of Organic Selenium and Tellurium Compounds, Vol. I , Wiley, 1986, pp. 667-676. (51) M. Michalska, J. Borowiecka, P. Lipka, and T. Rokia-Trygub0wicz.J. Chem. SOC.Perkin Trans. 1 (1989) 1619-1622. (52) M. M. Joullie, P. C. Wang, and J. E. Semple, J. Am. Chem. Soc., 102 (1980) 887-889. (53) P. C. Wang, Z. Lysenko, and M. M. JoulliC, Heferocycles, 9 (1978) 753-755. (54) J. Dupuis, B. Giese, D. Ruegge. H. Fischer, H. G. Korth, and R. Sustmann, Angew. Chem., Int. Ed. Engl., 23 (1984) 896-898. (55) M. Petrzilka. Helv. Chim. Acm, 61 (1978) 2286-89 and 3075-3078. (56) R. Pitteloup and M. Petrzilka, Helv. Chim. Acru, 62 (1979) 1319-1326. (57) D. G. Garatt, Can. J. Chem., 56 (1978) 2184-2187. (58) A. P. Kozikowski, K. L. Sorgi, and R. J. Schmiesing, J. Chem. SOC., Chem. Commun. (1980) 477-479. (59) A. P. Kozikowski, R. J. Schmiesing, and K. L. S0rgi.J. Am. Chem. Soc., 102 (1980) 65776580. (60) G. Jaurand, J.-M. Beau, and P. Sinag, J. Chem. Soc., Chem. Commun. (1981) 572-573. (61) A. Kaye, S. Neidle, and C. B. Reese, Tetrahedron Lett., 29 (1988) 2711-2714.

SELENIUM-CONTAINING SUGARS

197

M. Perez and J. M. Beau, Tetrahedron Lett., 30 (1989) 75-78. A. El Laghdach, Y. Diaz, and S. Castillon, Tetrahedron Lett., 34 (1993) 2821-2824. A. El Laghdach, M. I. Matheu, and S. Castillon, Tetrahedron, 50 (1995) 12219-12234. D. Horton, W. Priebe, and M. Sznaidman, Curbohydr. Res., 205 (1990) 71-86. A. Hassner and A. S. Amareseka, Tetruhedron Letr., 28 (1987) 5185-5188. M. Tingoli, M. Tiecco, D. Chianelli, R. Balducci, and A. Temperini, J. Org. Chem., 56 (1991) 6809-6813. (68) S. Czernecki, E. Ayadi, and D. Randriamandimby,J. Org. Chem., 59 (1994) 8256-8260. (69) R. M. Giuliano, R. S. Davis, and J. Boyko, J. Curbohydr. Chem., 13 (1994) 1135-1143. (70) F. Santoyo-Gonzalez, F. G. Calvo-Flores, P. Garcia-Mandoza, F. Hernandez-Mateo, J. Isac-Garcia, and R. Robles-Diaz, J. Org. Chem., 58 (1993) 6122-6125. (71) S. Czernecki and D. Randriamandimby, Tetrahedron Lerr., 34 (1993) 7915-7916. (72) F. Minisci and R. Galli, Tetrahedron Lett., 12 (1962) 533-538. (73) F. Santoyo-Gonzalez, F. G. Calvo-Flores, P. Garcia-Mandoza, F. Hernandez-Mateo, J. Isac-Garcia, and R. Robles-Diaz, Curbohydr. Rex, 260 (1994) 319-321. (74) S. Czernecki and E. Ayadi, Can. J. Chem., 73 (1995) 343-350. (75) H. Bayley, D. N. Stranding, and J. R. Knowles, Tetrahedron Lett., 39 (1978) 3633-3634. (76) H. Paulsen, Chem. SOC. Rev., 13 (1984) 15-45. (77) J. Banoub, P. Boullanger, and D. Lafont, Chem. Rev., 92 (1992) 1167-1195. (78) S. Czernecki, E. Ayadi, and D. Randriamandimby, J. Chem. Soc., Chem. Commun. (1994) 35-36. (79) E. Chelain, S. Czernecki, M. Chmielewski, and Z. Kaluza, J. Curbohydr. Chem., 15 (1996) 571-579. (80) S . Mehta and B. M. Pinto, Tetrahedron Lett., 32 (1991) 4435-4438. (81) H. M. Zuurmond, P. A. M. van der Klein, P. H. van der Meer, G. A. van der Marel, and J. H. van Boom, Rec. Truv. Chim. Pays-Bus, 111 (1992) 365-366. (82) S. Mehta and B. M. Pinto, J. Org. Chem., 58 (1993) 3269-3276. (83) H. M. Zuurmond, P. H. van der Meer, P. A. M. van der Klein, G. A. van der Marel, and J. H. van Boom, J. Curbohydr. Chem., 12 (1993) 1091-1103. (84) D. R. Mootoo, P. Konradsson, U. Udodong, and B. Fraser-Reid, J. Am. Chem. Soc., 110 (1988) 5582-5584. (85) D. R. Mootoo, P. Konradsson, U. Udodong, and B. Fraser-Reid, J. Am. Chem. Soc., 111 (1989) 8540-8542. (86) H. M. Zuurmond, P. A. M. van der Klein, J. de Wildt, G. A. van der Marel, and J. H. van Boom, J. Curbohydr. Chem., 13 (1994) 323-329. (87) L. A. J. M. Sliedregt, H. J. G. Broxterman, G. A. van der Marel, and J. H. van Boom, Curbohydr. Lett., 1 (1994) 61-68. (88) J. Kihlberg, E. Eichler, and D. R. Bundle, Curbohydr. Res., 211 (1991) 59-75. (89) S. Nilsson, H. Lonn, and T. Norberg, Glycoconjugute J., 8 (1991) 9-15. (90) K. Linck, J. Alfoldi, and J. Defaye, Curbohydr. Res., 164 (1987) 195-205. (91) J. M. J. Tronchet, N. Bizzozero and F. Barbalat-Rey, J. Curbohydr. Chem., 6 (1987) 155- 160. (92) For a review see: J. Defaye and J. Gelas in Atta-ur-Rahman (Ed.), Studies in Natural Products Chemistry, Elsevier, Amsterdam, Vol. 8 (1991) 315-357. (93) Y. Wang, S. A. Babirad, and Y. Kishi, J. Org. Chem., 57 (1992) 468-481. (94) P. Laltgerie, G. Legler, and D. M. You, Biochemie, 64 (1982) 997-1005. (95) S. Czernecki and D. Randriamandimby, J. Curbohydr. Chem., 15 (1996) 183-190. (96) P. L. Durette and T. Y. Shen, Curbohydr. Res., 81 (1980) 261-274. (97) P. J. Garegg and B. Samuelson, J. Chem. SOC. Perkin Trans. 1 (1980) 2866-2869. (97a) R. S. Tipson and A. Cohen, Curbohydr. Res., 1 (1965) 338-340. (62) (63) (64) (65) (66) (67)

198

ZBIGNIEW J. WITCZAK AND STANISLAS CZERNECKI

(97b) E. Albano, D. Horton, and T. Tsuchiya, Carbohydr. Res., 2 (1966) 349-362. (98) H. Paulsen, F. R. Heiker, J. Feldmann, and K. Heyns, Synthesis (1980) 636-638. (99) Y.Nishimura, H. Umezawa, and S. Umezawa, Tetrahedron Lett. (1981) 77-80. (100) P. Rollin, V. Verez Bencomo, and P. Sinay, Synthesis (1984) 134-135. (101) J. M. Lancelin, J. R. Pougny, and P. Sinay, Carbohydr. Res., 136 (1985) 369-374. (102) P. A. Grieco, J. Y. Jaw, D. A. Claremon, and K. C. Nicolaou, J. Org. Chem., 46 (1981) 1215-1217. (103) K. C. Nicolaou, N. A. Petasis, and D. A. Clareman, Tetrahedron, 41 (1985) 4835-4841. (104) P. A. Grieco, S. Gilman, and M. Nishizawa, J. Org. Chem., 41 (1976) 1485-1486. (105) P. A. Grieco, Y. Yokoyama, and E. Williams, J. Org. Chem., 43 (1978) 1283-1285. (106) P. A. Grieco, E. Williams, H. Tanaka, and S. GilmanJ. Org. Chem.,45 (1980) 3537-3539. (107) H. Takaku, T. Nomoto, and K. Kimura, Chem. Lett., (1981) 1221-1224. (108) A. P. Kozikowski and A. Ames, Tetrahedron, 41 (1985) 4821-4834. (109) D. J. Morgans, Jr., Tetrahedron Lett., (1981) 3721-3724. (110) M. J. Gender, S. Chan, and D. B. Ball, J. Am. Chem. SOC.,97 (1975) 436-437. (11 1) R. Noyori, T. Sato, and Y. Hayakawa, J. Am. Chem. Soc., 100 (1978) 2561-2563. (112) R. Noyori, T. Sato, Y. Hayakawa, and R. Ito, Tetrahedron Left., (1978) 1829-1830. (113) K. Suzuki and T. Mukaiyama, Chem. Lett, (1982) 683-688. (114) A. B. Reitz, S. 0. Nortey, B. E. Maryanoff, D. Liotta, and R. Monahan, 111, J. Org. Chem., 52 (1987) 4191-4202. (115) R. M. Adlington, J. E. Baldwin, A. Basak, and R. P. Kozyrod, J. Chem. Soc., Chem. Commun. (1983) 944-945. (116) G. E. Keck and J. B. Yates, J. Am. Chem. Soc., 104 (1982) 5829-5831. (117) P. J. Kocienski, Tetruhedron Len., (1980) 1559-1563. (118) K. C. Nicolaou, Tetrahedron, 37 (1981) 4097-4109. (119) P. D. Kane and J. Mann, J. Chem. SOC., Chem. Cornmun. (1983) 226-244; J. Chem. SOC. Perkin Trans. 1 (1984) 657-660. (120) F. Freeman and K. D. Robarge, Curbohydr. Res., 137 (1985) 89-97. (121) F. Freeman and K. D. Robarge, J. Org. Chem., 54 (1989) 346-359. (122) J. L. Fourrey, G. Henry, and P. Jouin, Tetrahedron Lett. (1980) 455-458. (123) R. A. Raphael, I. H. A. Stibbard, and R. Tidbury, Tetrahedron Lett. (1982) 2407-2409. (124) G . Jaurand, J. M. Beau, and P. Sinay, J. Chem. Soc., Chem. Commun. (1981) 701-703. (125) K. Furuichi, S. Yogai, and T. Miwa, J. Chem. Soc., Chem. Commun. (1980) 66-68. (126) T. Sakakibara, J. Takai, E. Ohara, and R. Sudoh, J. Chem. SOC., Chem. Commun. (1981) 261-262. (127) T. Sakakibara, Y. Nomura, and R. Sudoh, Carbohydr. Res., 124 (1983) 53-62. (128) G. Berube, E. Luce, and K. Jankowski, Bull. SOC. Chim. Fr., 2 (1983) 109-111. (129) A. G. M. Barrett, R. W. Read, and D. H. R. Barton, J. Chem. SOC., Perkin Trans. I (1980) 2184-21 90. (130) A. G. M. Barrett and H. B. Broughton, J. Org. Chem., 49 (1984) 3673-3674. (131) B. P. Mundy and W. G. Bornmann, J. Org. Chem., 49 (1984) 5264-5265. (132) S. David, A. Lubineau, and J. M. VatB1e.J. Chem. Soc., Chem. Commun. (1975) 701-702. (133) S. David, A. Lubineau, and J. M. VatB1e.J. Chem. Soc., Perkin Trans. 1(1976) 1831-1837. (134) K. Torssel and M. P. Tyagi, Act0 Chem. Scand., Ser. B, 31 (1977) 297-301. (135) S. David and A. Lubineau, Nov. J. Chem., 1 (1977) 375-379. (136) K. Ikeda, S. Akamatsu, and K. Achiwa, Carbohydr. Rex, 189 (1989) Cl-C4. (137) A. G. M. Barret, H. B. Broughton, S. V. Attwood, and A. A. L. Gunatilka, J. Org. Chem., 51 (1986) 495-503. (138) Y.Ito and T. Ogawa, Tetrahedron Lett., 28 (49) (1987) 5221-5224. (139) M. Solomon, W. Hoekstra, G. Zima, and D. Li0tta.J. Org. Chem.,53 (1988) 5058-5062.

SELENIUM-CONTAINING SUGARS

199

(140) D. Crich and T. J. Ritchie, J. Chem. SOC.,Chem. Commun. (1988) 1461-1463. (141) B. Giese, T. Liuker, and R. Muhn, Tetrahedron, 45 (1989) 935-940. (142) B. Giese, S. Gilges, K. S. Groninger, C. Lamberth, and T. Witzel, Liebigs Ann. Chem. (1988) 615-617. (143) H. G. Korth, R. Sustmann, J. Dupuis, and B. Giese, J. Chem. Soc., Perkin Tram. I1 (1986) 1453-1459. (144) A. DeMesmaeker, P. Hoffman, B. Ernst, P. Hug, and T. Winkler, Tetrahedron Lett., 30 (1989) 6311-6314, and Tetrahedron Lett., 30 (1989) 6307-6310 (a). Synlett (1992) 285-290. (145) S. Czernecki, unpublished data. (146) S. Murata and T. Suzuki, Chem Lett., 5 (1987) 849-852. (147) M. R. Huckstep and R. J. K. Taylor, Tetrahedron Lett., 27 (1986) 5919-5922. (148) T. Wilson, P. Kocienski, A. Faller, and S. Campbell, J. Chem. Soc., Chem. Commun. (1987) 106-108. (149) G. Mehta, H. S. P. Rao, and K. Raja Reddy, J. Chem. Soc., Chem. Commun. (1987) 78-80. (150) A. Kaye, S. Neidle, and C. B. Reese, Tetrahedron Lett., 29 (22) (1988) 2711-2714. (151) A. Kjax and T. Skrydstrup, Acta Chem. Scand., B41 (1987) 29-33. (152) D. Goldsmith, D. Liotta, C. Lee, and G. Zima, Tetrahedron Lett., 19 (1979) 4801-4804. (153) S. V. Ley, B. Lygo, H. Molines, and J. A. Morton, J. Chem. Soc., Chem. Commun. (1982), 1251-1252. (154) G. Stork and G. Kim, J. Am. Chem. Soc., 114 (1992) 1087-1088. (155) Y.C. Xin, J. M. Mallet, and P. Sinafi, J. Chem. Soc., Chem. Commun. (1993) 864-865. (156) B. Vauzeilles, D. Carvo, J. M. Mallet, and P. Sinafi, Synlett (1993) 522-523. (157) A. Mallet, J. M. Mallet, and P. Sinafi, Tetrahedron Asymmetry, 5 (1994) 2593-2608.

This Page Intentionally Left Blank

ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL. 53

ANTI-CARBOHYDRATE ANTIBODIES WITH SPECIFICITY FOR MONOSACCHARIDE AND OLIGOSACCHARIDE UNITS OF ANTIGENS

BY JOHNH. PAZUR Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802

I. Introduction

.......................................................

201

.. . . . . . . . . . . . . . . . . . . . , . . . . .. . . . . . . . . . . . . . . . . . . . . 203 1. Affinity Chromatography. . . . . . . . , . . . . . . . . . . . . . . , . . . . , . , . . .. . . . . . . . . 203 2. Agar Diffusion. .... .. ..................... ..................., ,. . 205 3. Electrofocusing and Electrophoresis . . . . . . . . , . . . . . . . . . . . . . . . .. . . . . . . . . 206 4. Ultracentrifugation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206 5. Inhibition ....................................................... 208 208 6. Other Methods ................................................... 111. Preparation of Antigens Containing Carbohydrate Residues. , . , . . . . . . . . . . . . . . 209 1. Polysaccharides. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . 209 2. Glycoproteins .................................................... 210 211 3. Glycoconjugates .................................................. IV. Immunization Procedure. . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212 V. Preparation and Properties of Anti-carbohydrate Antibodies , , . , . . . . . . . . . . . . . 213 1. Specificity for Monosaccharides: (Y-D-GIC, P-o-Glc, P-D-Gal, a-D-Man, 1-Thio-ao-Man, (Y-L-FUC, P-D-GIcA,p-D-Xyl, P-o-GalA, a-L-Rha, P-D-GIcNAc. . . . . . . . 213 11. Analytical Methods..

2. Specificity for Oligosaccharides: p-o-Gal-( 1 -+ 4)-~-Glc,a-o-Glc-( 1 + 6)-o-Glc (Myeloma), P-o-GlcA-(l + 3)-o-GaI (Gum Arabic), P-L-Ara-(l + 4)-~-GlcA (Gum Arabic), 4,6-Pyruvate-o-Man-(I + 4)-o-GkA (Xanthan), Man,, (Glucoamylase), Fuc,-(Tumor). 3. Specificity for Hexose I-Phosphates and Others: P-o-Glc-1-P, P-o-Glc NAc-1-P, Shigella LPS, Others.. . .. VI. Conclusions........................................................ References ........................................................

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231 . . . . . . . . . . . . . . . .. . . . . . . . . . . .. . . . . . . . . . . . . . 250 254 258

I. INTRODUCTION Anti-carbohydrate antibodies are those antibodies synthesized in the circulatory system of vertebrates that have been immunized by antigens containing carbohydrate units. Such carbohydrate components initiate an immune response and activate a specific number of circulating plasma 036.5-2318198 rE2S.IX)

201

Copyright 0 1998 by Academic Press. All rights of reproduction in any form reSeNed.

202

JOHN H. PAZUR

cells with receptor sites for carbohydrate The antibodies possess specificity for carbohydrate residues present as structural components of the antigen. These antibodies occur in sets of multimolecular forms and may be appropriately called is~antibodies.~ The definition of isoantibodies herein is different from that employed by immunologists,' but is in line with isoenzymes, a terminology which is employed by enzymologists for All members of a set possess the same multimolecular forms of enzyrne~.~ specificitybut differ in molecular s t r ~ c t u r eThe . ~ anti-carbohydrate antibodies discussed in this article are polyclonal,6 and these antibodies, like monoclonal antibodies,7.8have many applications. The antibodies are useful as diagnostic markers for detecting carbohydrate antigens in diseased tissues? as analytical reagents for determining constituents in food items," and as models for studying genetic aspects of the biosynthesis and assembly of the light and heavy chains of antibodies.6 The first step in the preparation of anti-carbohydrate antibodies is the immunization of animals with an antigen containing carbohydrate units in the molecular structure. Several cycles of immunization are required for obtaining serum that contains high levels of anti-carbohydrate antibodies. With the advances in chromatography" it is now possible to isolate and purify anti-carbohydrate antibodies by the affinity chromatography method developed initially for the purification of enzymes.12To isolate the antibodies, the serum is subjected to affinity chromatography on an adsorbent bearing ligands of structure identical to the immunodeterminant group of the antigen. The adsorbents with carbohydrate ligands can be synthesized by attaching carbohydrates or carbohydrate derivatives to insoluble polymeric supports, using the cyanogen bromide13 or the carbodiimide method.I4 The carbohydrate-containing compounds that have been used as antigens include polysaccharides from bacterial cell wallsI5 and from plant gums,I6 glycoproteins from fungi" and from human diseased tissue,I8J9and several types of synthetic glycoconjugates.20The antigens of the first two types were isolated from natural sources. The glycoconjugates are synthesized from bovine serum albumin and various protein carriers and carbohydrate derivatives. Methods for the isolation and synthesis of carbohydrate antigens are given in Section 111. In chemical structure, the antibodies are glycoproteins containing a low percentage of carbohydrate.21 In structure the antigens may be polysaccharides, glycoproteins, glycolipids, nucleic acids, or carbohydrate conjugates.' The purification and characterization of the following anti-carbohydrate antibodies with specificity for monosaccharides, oligosaccharides, and glycosy1 phosphates has been accomplished. The carbohydrate residues are abbreviated by the conventional manner: U-D-GIC,P-D-G~c, P-D-Gal, (Y-DMan, a-1-thio-a-D-Man, P-D-G~cA, a-L-FUC,P-D-Xyl, P-D-GalA, a-L-Rha, P-D-G~cNAc,P-D-Gal-(1 + 4)-~-Glc,a-~-Glc-( 1 + 6)-~-Glc,P-D-G~cA(1 + 3)-~-Gal,P-L-Ara-(l + 4)-~-GlcA,4,6-pyruvate-P-~-Man-(l+ 4)-

ANTI-CARBOHYDRATE ANTIBODIES

203

D-G~cA, p-~-Glc-l-P,p-~-GlcNAc-l-P.The isolation and characterization methods which are used in the author’s laboratory are outlined. Novel aspects of antigen structure and antibody specificity for carbohydrates are stressed. Some medical and technological applications are also recorded. 11. ANALYTICAL METHODS

1. Affinity Chromatography a. General Consideration.-The theoretical aspects and the details of performing affinity chromatography for purifying macromolecules are presented briefly in this section. Affinity chromatography is performed on columns of insoluble adsorbents consisting of a support to which are attached ligands which bind the macromolecules being purified. The method requires the preparation of a suitable adsorbent bearing ligands that form a complex with the substance being isolated. A solvent system which releases the desired substance from the ligand needs to be available or readily prepared. The formation of the complex should be specific and reversible, with the latter being necessary for the release of the antibody at a later stage. The serum containing the antibody is prepared by immunization of selected animals with the antigen. The serum obtained is passed through the column of adsorbent containing ligands specific for the antibody. The compounds in the serum which do not bind to the ligand will pass unretarded through the adsorbent, and those which bind to the ligand are immobilized on the support. The antibody is released later from the complex by the solvent containing an agent with a structure complementary to the active site of the antibody or by a nonspecific chaotropic agent. b. Affinity Adsorbents.-The selection of the type of support material and of the ligand are critical to the successful performance of affinity chromatography. A number of insoluble polymers of carbohydrates or other organic compounds possess the desirable properties. The support material should be insoluble, possess good porosity, and be reactive with the ligands. Sepharose, a p-(1 + 3)-linked polymer of D-galactose and 3,6-anhydro-~-galactose; Sephadex, an a-(1+ 6 ) polymer of D-glucose; cellulose, a p-(1+ 4) polymer of D-glucose; and starch, an a-(1+ 4) and (1-+ 6 ) polymer of D-glucose,are All of these support materials have been used and most are available commercially. The component residues of these polymers have been cross-linked to varying degrees to yield adsorbents with improved properties. Cross linkages are introduced by reacting polymers with such agents as epichlorohydrin, thereby forming a chemical linkage between the hydroxyl groups of carbohydrate units of different chains of the polymer. The degree of cross-linking in different supports is variable. Polyacrylamide gel is another material that has been

204

JOHN H. PAZUR

used effectively as a support material. The coupling of compounds may be enhanced by first attaching an organic group (the arm) to the support and then attaching the ligand. Procedures are available for this atta~hment.’~,’~ Several methods have been devised for attaching ligands to the insoluble supports. Thus, Sepharose is converted to an activated form by reaction with cyanogen bromide.13The product is reactive with many types of carbohydrate derivatives, yielding an adsorbent carrying the desirable ligand. For the attachment of carbohydrate units to the CNBr-activated support, the carbohydrates must contain free primary amino groups or must be converted into derivatives having a primary amino group. p-Aminophenyl glycosides are widely used for this purpose and are available from commercial suppliers. A reaction occurs between the cyanoester of activated Sepharose and the amino group of the glycoside. Another reaction for attaching ligands to supports is the carbodiimide reaction. In this method, activated Sepharose is used to prepare Sepharose containing amino or carboxyl groups. The latter is realized by reacting cyanogen bromide-activated Sepharose with lY6-diaminohexaneor 6-aminohexanoic acid. Ligands containing carboxyl groups will react with the former and ligands having amino groups will react with the latter. The carbodiimide r e a ~ t i o n catalyzes ’~ both types of reactions, yielding an adsorbent with the desirable ligand. Other methods of attaching ligands to insoluble supports have been devised, these include reductive aminati~n?~ epoxy a~tivation?~ alkylglycoside reaction, and reduction.” c. Protocol for Afhity Chromatography.-An illustration of the affinity chromatography method is described in which the isolation of antirhamnose antibodies is achieved. The antibodies are specific for an antigen of a polysaccharide from the cell wall of the Streptococcus mutans.26The antigen was isolated from the cell wall, and methylation analysis showed that the polysaccharide is composed of rhamnose, glucose, and galactose. The immune serum was obtained from a rabbit immunized with nonviable cells of S. mutuns. The serum was used for affinity chromatography as follows. A sample 1 ml of the serum is introduced onto the rhamnosylSepharose column. After adsorption of the serum, the column is washed with 0.02 M phosphate buffer of pH 7 in saline. The unbound proteins and other constituents are removed, and the antibodies are retained. The antibodies are then eluted with 0.1 M L-rhamnose. The eluate is continuously monitored for UV-absorbing components at 280 nm with a UV monitor from the begining of the chromatography. The elution pattern is reproduced in Fig. 1. The UV-absorbing component that is eluted by a solution of L-rhamnose is collected. The sample is mixed with an equal voume of saturated ammonium sulfate. On refrigeration overnight, a precipitate is

ANTI-CARBOHYDRATE ANTIBODIES

205

FIG.1 .-Affinity chromatography elution pattern for anti-rhamnose antibodies in immune serum from Sfrepfococcusm u m s . The arrows indicate the point of application of the serum and of 0.5 M L-rhamnose solution. The inset is an agar-diffusion pattern of the antibodies against the antigen. (Reprinted from CurbohydrufeResearch, Volume 124, J. H. Pazur, M. S. Erikson, M. Tay, and P. Z. Allen, pp. 253-263, copyright 1983, with permission from Elsevier Science Ltd., The Boulevard, Langford Lane, Kidlington OX5 lGB, UK.)

formed in the solution, and this precipitate is recovered by centrifugation. The precipitate is dissolved in a small volume of 0.02 M phosphate buffer, pH 7 in saline. Several such samples are prepared, combined, and then concentrated by ultrafiltration. The latter sample is checked for antibody activity by agar diffusion against the rhamnosyl polysaccharide of S.rnufuns. The results are shown in the inset of Fig. 1. 2. Agar Diffusion

A method used extensively for the identification and characterization of antibodies is agar diffusion. The method was originally devised by Ouchterl ~ n y . ’The ~ procedure is readily performed on a microscope slide. Agarose (0.5 g) is suspended in 50 mL of 0.1 M phosphate buffer of pH 7.0 and 5 mg of merthiolate is added. The mixture is heated to boiling until the agarose is in solution. To prepare a slide, a hot solution of agar is introduced in a thin layer on the slide. The agar is allowed to solidify and wells are punched at appropriate distances apart in a circular fashion on the slide with a well puncher. The plug of agar is withdrawn by suction and immune serum or purified antibodies are placed in the center wells. A solution of the antigen at concentrations of 0.2 to 1%is placed in the outer wells. The slide is placed on moist filter paper in a petri dish, and the dish is covered.

206

JOHN H. PAZUR

Diffusion is allowed to proceed for timevarying from 6 to 24 h. Visible precipitin bands develop on the plate (Fig. 2), and the plate is photographed for a permanent record and for comparison with results obtained in other tests. 3. Electrofocusing and Electrophoresis Gel isoelectrofocusing is performed on the antibody samples in 10% polyacrylamide gels in ampholine-sucrose solutions of pH 5 to 8, 5 to 7, or 4 to 6 gradients by the procedure described in the literature.28 The electrophoresis is performed essentially as described by Davis.29Electrofocusing, or electrophoresis coupled with agar diffusion, was devised to check for the formation of a precipitin complex by the antibody preparation and the antigen. In this procedure, duplicate samples of antibody preparation are subjected to identical isoelectrofocusing or electrophoresis. One finished gel is stained for protein with Coomassie Blue and the other gel is embedded in fluid agar. When the agar solidifies, a trough is cut in the agar about 2 cm from the gel and a 2% solution of the antigen is placed into the trough. Diffusion is allowed to proceed for 24 to 48 h and plates which develop precipitin bands are photographed. Results with a glycoprotein, glucoamylase?' are recorded in Fig. 3.

4. Ultracentrifugation The molecular size and molecular homogeneity of antibodies may be determined by a sucrose density-gradient ultracentrifugation method."'.'* Samples of 0.2 mL of 0.4% solutions of each antibody preparation are placed carefully on top of separate sucrose density-gradient tubes prepared from 5,10,20,30, and 40% sucrose. The tubes are centrifuged in a swinging

FIG.2.-Agar-diffusion pattern of immune serum (Ab) and antigenic polysaccharides from Streptococcus faecafis. Wells 1 and 2 contain a tetraheteropolysaccharide, wells 3 and 4 contain a diheteropolysaccharide,and wells 5 and 6 contain a mixture of the two antigenic polysaccharides. [From J. H. Pazur in Carbohydrate AnalyskA Practicul Approach, (M. F. Chaplin, J. F. Kennedy, eds.) IRL Press, Oxford, England, 1986, pp. 55-96, by permission of Oxford University Press.]

ANTI-CARBOHYDRATE ANTIBODIES

207

FIG. 3.-Gel electrophoresis and agar diffusion. 1 = gel stained for protein; 2 = gel embedded in agar; 3 = precipitin band; 4 = glucoamylase antigen.

bucket SW 65 rotor at 65,000 rpm for 14 h in a Beckman L-65 ultracentrifuge. At the end of this time the tubes are removed and the gradient solutions are fractionated into 0.2-mL samples by means of an ISCO Density Gradient Fra~tionator.~' The UV absorbance of the eluate from the densitygradient columns is determined continuously at 280 nm from the beginning of the fractionation. The sedimentation patterns for anti-fucose antibodies, immune serum, and glucose oxidase are r e p r ~ d u c e din~Fig. ~ 4.The molecu-

f

Glc Ox ,, 1 lj I

0

I

1

I

2

I

3

I

I

4

d

I

S

DETANCE (an) FIG.4.-Ultracentrifugation in sucrose-density gradients: Se = immune serum; Ab = antibody; Glc-Ox = o-glucose oxidase. (Reprinted from Carbohydrate Research, Volume 124, J. H. Pazur, M. S. Erikson, M. Tay, and P. Z. Allen, pp. 253-263, copyright 1983, with permission from Elsevier Science Ltd., The Boulevard, Langford Lane, Kidlington OX5 lGB, UK.)

208

JOHN H. PAZUR

lar weights of the antibodies were calculated using glucose oxidase as a standard (MW = 1.54 X 105)34and an empirical formula35and was found to be 1.5 X lo5.

5. Inhibition The specificity of the antibodies can be verified by hapten-inhibition tests; the results of experiments with anti-lactose antibodies are shown36 in Fig. 5. In this test, a sample of the antibody is first incubated with the potential inhibitor for 2 h at room temperature. Appropriate amounts of the digest and the pure antibody sample are placed in the separate center wells of an agar plate. Decreasing amounts of antigen (20 to 1 pg) are placed in outer wells (1to 6). Agar diffusion is used to detect the formation and the number of precipitin bands. A comparison of the amount of antigen required to give the same amount of precipitin with the native antibody and the antibody treated with inhibitor permits calculation of the percentage of inhibition. 6. Other Methods Immunoglobulin type, reactivity with chemically modified antigens, and carbohydrate content of antibodies may also be determined. In determination of the Ig type it was found that all antibodies react with goat antirabbit IgG and not against rabbit IgA or IgM. The antibodies are therefore of the IgG type of imm~noglobulin.~’Periodate oxidation, oxidation by

FIG.S.-Inhibition of anti-lactose antibodies reacting with an antigenic polysaccharide from a Group D Streptococcus in the presence or absence of inhibitors: well A = anti-lactose antibodies; well B = antibodies with lactose; well C = antibodies with galactose; wells 1-6 contain the antigen at decreasing concentrations from 20 to 1 pg. (Reprinted from Journal oflmmunological Methods, Volume 75, J. H. Pazur, and S. A. Kelly, pp. 107-116, copyright 1984 with kind permission of Elsevier Science-NL, Sara Burgerhartstraat 25, 1055 KV Amsterdam, The Netherlands.)

ANTI-CARBOHYDRATE ANTIBODIES

209

peroxypropanoic acid, acid hydrolysis, and borohydride reduction are used for modifying the antigens. The carbohydrate content of antibodies is determined in acid hydrolyzates by paper c h r ~ m a t o g r a p h yand ~ ~ by standard colorimetric methods3' The details are presented in Section V. 111. PREPARATION OF ANTIGENS CONTAINING CARBOHYDRATE RESIDUES

1. Polysaccharides Many microbial polysaccharides, when mixed with Freund's complete adjuvant and injected into animals, are antigenic. In microorganisms, the polysaccharides are embedded in the outer layer of the cell wall together with glycosaminopeptides and teichoic acids.40Extraction of the polysaccharides from the cell wall may be performed on cell-wall fragments or on whole cells. In the former case the cells must be broken by grinding with glass beads and then isolating the cell-wall fragments by differential centrifugation. The polysaccharides in the cells or fragments may then be extracted with various solvents, such as aqueous trichloracetic acid,"* KClHCI buffer OF*pH 2, or f ~ r m a m i d eThe . ~ ~ resulting extracts are treated with a protease and RNAase to hydrolyze protein and nucleic acid contaminants. The polysaccharide in the extract is then precipitated with several volumes of acetone and purified by fractional precipitation with ethyl alcohol. There are microorganisms that produce extracellular polysaccharides which may be antigenic4 The production of such a polysaccharide for isolation purposes involves serial growth of the organism on the proper medium to obtain a good yield of organisms. The cells are then inactivated by heat and removed. The broth is used for isolating the polysaccharide; it is mixed with several volumes of ethyl alcohol and the precipitate (which contains impurities) is allowed to settle and removed by centrifugation. The alcohol supernatant is concentrated by evaporation and the concentrate is dried by lyophilization. The dried product is the purified polysaccharide. Polysaccharides from plants have been prepared by a number of methods. Polysaccharides are present in the seeds45of the plant or in exudate^^^.^^^ of shrubs. If seeds are used, it is necessary to grind the seed before extraction of the polysaccharides. Extraction by distilled water or a suitable buffer is used. The extracts so obtained may contain a small amount of flocculent material, which is allowed to settle and is removed by centrifugation. The supernatant solution is then treated with several volumes of 95% alcohol. A white precipitate of the polysaccharide is formed, and this precipitate is collected by centrifugation. The precipitate is dehydrated with absolute

210

JOHN H. PAZUR

alcohol and dried in a vacuum for use. Plant gums collected from shrubs may be purified by similar procedures. 2. Glycoproteins

There are many types of glycoproteins in biological materials, and these compounds vary greatly in structure. Accordingly, there are many isolation procedures which have been used. Diseased human tissue often contains unusual glycoproteins.The isolation of such glycoproteins from colon tumor tissue is described. Tumor tissue can be secured from patients with the disease by the attending physician. Samples of normal tissue should also be obtained from the organ. The tumor specimens are dissected as cleanly as possible to remove adhering normal tissue. The sample is extracted by pH 2. In the perchloric 1.2 M perchloric acid’* or by 0.01 M KCl-HC1 acid method the tissue is homogenized in two volumes of 1.2 M perchloric acid in a Waring blender for 10 min. Following the homogenization in distilled water, the suspension is separated from the large tissue fragments by decantation. An equal volume of 1.2 M perchloric acid is added and the resulting suspension is stirred vigorously at room temperature for 5 h. The extract is clarified by centrifugation at 4300 g for 15 min. The precipitate is discarded and the supernatant saved for further treatment. Any lipid particles in the supernatant are also removed by centrifugation at 20,000 g for 15 min and siphoning off by suction. The remaining solution is dialyzed against distilled water at 4°C for 40 h. The clear filtrate is lyophilized to dryness and constitutes the final tumor extract. A similar extraction and treatment of a comparable amount of normal tissue is performed. A second sample of the tumor tissue is extracted with KCl-HCl solution (0.05 M KCl and 0.01 M HC1 of pH 2). First the tissue is homogenized in two volumes of the KC1-HCl solution in a Wanng blender for 15 min. This homogenate is subjected to a treatment similar to that for the perchloric acid homogenate. An extract of normal tissue is also prepared by the KCl-HCl method. Microbial enzymes elaborated by bacteria and fungi often possess glycoprotein structure. Glucoamylase from Aspergilus niger is a valuable enzyme commercially and will be used as an example.” This enzyme is used in commercial production of glucose and high-fructose syrups from starch. These products are used as ingredients in many food items and pharmaceuticals. Glucoamylase is a glycoprotein containing mannose, glucose, and galactose. This enzyme is an excellent model for investigating the synthesis of antibodies initiated by a glycoprotein. To prepare the glucoamylase, A.

ANTI-CARBOHYDRATE ANTIBODIES

21 1

niger is grown on mineral media supplemented with glucose for periods of several days.47The culture contents are pressed through cheesecloth to remove the mycelium, and the filtrate is stirred with four volumes of cold ethyl alcohol for 1 h. The precipitate that forms is collected by decantation and centrifugation. The precipitate from 3.5 L of culture filtrate is dissolved in 200 mL of citrate-phosphate buffer of pH 8.0, and the solution is subjected to chromatography on DEAE-~ellulose.'~ The proteins in the filtrate are adsorbed on the DEAE-cellulose and are then eluted with 500 mL of citrate buffer of pH 6 and finally with 500 mL of citrate buffer of pH 4. Fractions of 10-15 mL of the eluate are collected. Activity and pH measurements show that the glucoamylase is present in fractions of pH 5.5-6.0 and in fractions of pH 4.5-5.0. Evidently A. niger produces two isoenzymesof glucoamylase,and these can be separated by DEAE-cellulose chromatography. Since the enzyme eluted at pH 4.5 is present in greater amount, this isoenzyme has been used as the enzyme representative of the glucoamylase group. The fractions at pH 4.5-5.0 containing the glucoamylase are combined (50 mL) and stirred with four volumes of ethyl alcohol. The precipitate that forms settles on refrigeration and is collected by centrifugation. This precipitate is dissolved in 5 mL of citrate-phosphate buffer at pH 6 and assayed for enzyme activity and used for immunological studies. The enzyme is extremely stable and can be maintained for long periods with little loss of activity.

3. Glycoconjugates The glycoconjugates of carbohydrates and proteins are useful antigenic substances for initiating the synthesis of anti-carbohydrate antibodies. These conjugates may be prepared by a number of reaction routes. A general route utilizes the carbodiimide reaction for couplingp-aminophenyl glycosides to proteins (bovine serum protein, horse serum globulin, ovalbumin, lactoalbumin, or gamma globulin). The carbodiimide is the catalyst for the reaction and promotes the condensation between the free amino group of the glycoside and a free carboxyl group of the protein to form a new peptide bond.I4 Details for the preparation of a glycoconjugate of fucose-bovine serum albumin are given.33 A sample of 40 mg of 2aminophenyl a-L-fucopyranosideis dissolved in 2 mL of water slowly added to 5 mL of a 10% BSA solution. After adjusting the pH to 4.5 with HCI, 0.2 g of CMC l-[cyclohexyl-3-(2-morpholinoethyl)carbodiimidemetho-ptoluenesulfonate] in 2 mL of ethyl alcohol is added to the solution. The mixture is stirred for 16 h at room temperature, during which time coupling of the reactants occurs. The sample is then dialyzed against distilled water

212

JOHN H. PAZUR

for 24 h and the dialyzate is taken to dryness by lyophilization. Analysis of the sample by the cystein-HC1 method39yields a value of 11.5% deoxyhexose in the conjugate. The yield of the coupled product is 0.9 g. The p aminophenyl glycopyranosides of a-D-glucose, P-D-glucose, a-D-mannose, a-D-galactose, and a-L-rhamnose have been used with the protein carriers to prepare different glycoconjugates. IV. IMMUNIZATION PROCEDURE Animals to be used for immunological research show pronounced differences in their capacity to respond to specific antigens, including those containing carbohydrates. Such differences are genetically controlled and the selection of animals for immunization should be on the basis of a preliminary test. It is well to immunize a group of animals for short periods, and select those individuals which give the best response in preliminary trials for futher immunization and for production of antibodies. Immunization procedures vary and are dependent on type of antigen to be used, duration of immunization process, and the amounts of immune product needed. The antigen suspension may be administered intravenously, intramuscularly, or subcutaneously. The amount of antigen injected can range from 1 to 200 mg. The quantity is determined by the availability of and the potency of the antigen. The time schedule also varies. Protocols for the three types of immunizations used to produce anti-carbohydrate antibodies are recorded in the following. For intravenous injection, nonviable cells of microorganisms are used.48 Vaccines of Streptococcus faecalis, strain NC 3, are prepared from 500-mL cultures grown in Todd-Hewitt broth for 20 h at 37°C. Cells are recovered from the media by centrifugation at 6,000 X g for 15 min at 4°C. These cells are washed three times with saline and recovered after each washing by centrifugation. Cells are then shaken in 100 mL of 0.2% formaldehyde for 30 h at 4°C. Following formaldehyde treatment, the cells are recovered by centrifugation, washed twice with 50 mL of sterile saline, and collected by centrifugation. Finally, the cells are suspended in 100mL of sterile saline. The suspension may be diluted for immunization. Prior to immunizations, viability tests are conducted on the vaccines by inoculating different tubes containing 10 mL of sterile Todd-Hewitt broth with 0.1,0.2, and 0.5 mL of vaccine. A tube with a sample of viable streptococcal cells is also prepared. The tubes are incubated at 37°C and growth is monitored by measuring the absorbance at 600 nm after 12, 24, and 48 h of incubation. Growth should be observed in the control, but not in the formaldehyde-treated sample.

ANTI-CARBOHYDRATE ANTIBODIES

213

Four rabbits were used for immunizations with vaccine of equal parts of nonviable cells of S. fuecalis suspension and Freund’s complete adjuvant. Each week the rabbits are injected intravenously with 0.2 mL of the vaccine for 3 consecutive days, followed by a rest period of 4 days. This regime is performed for 5 weeks and is followed by a 1-week rest period. The immunization is performed in the same manner as before for 6 more weeks. Blood samples are drawn weekly after the fourth week of initial immunization. The serum is separated and tested by agar diffusion for the presence of antibodies. The intramuscular immunization is performed as follows!’ A solution containing gum arabic is prepared by dissolving 1 g of the gum in 10 mL of sterile 0.02 M phosphate buffer, pH 7.0 in saline. The resulting solution is mixed with an equal volume of Freund’s complete adjuvant. This suspension is thoroughly mixed and used to immunize rabbits by the following regime. A 0.4-mL sample of the gum-vaccine is injected intramuscularly in the hind leg of a rabbit. The injection is repeated weekly in alternate legs. After 6 weeks, the animals are allowed to rest for 2 weeks, following which the injection schedule is repeated. The schedule is repeated a third cycle. Blood samples are collected weekly in the second and subsequent cycles and sera are prepared by a standard method. The glycoconjugates were used in the subcutaneous method. Vaccines of glycoconjugates are prepared by dissolving 30 mg of the conjugate in 5 mL of sterile 0.1 M phosphate buffer and saline, pH 7.0. The solution is mixed with an equal volume of Freund’s complete adjuvant. The suspension is injected subcutaneously at multi-sites of the back according to the following regime.33Every week, for a period of 6 weeks, rabbits are injected with 2.0 mL of the vaccine distributed among 10 sites on the back of the rabbit. Trial bleedings are taken after the fourth injection. After a rest period of several weeks, the rabbits are given booster injections for a 5week period. Blood samples are drawn weekly after the booster injections. The blood is allowed to clot and serum is separated from the clot by centrifugation. The serum is stored frozen in sterile polypropylene tubes until used. V. PREPARATION AND PROPERTIES OF ANTI-CARBOHYDRATE ANTIBODIES

1. Specificity for Monosaccharides: a-D-GIC,P-D-GIc, P-D-Gal, a-D-Man, 1-Thio-a-D-Man, a-L-FUC,PD-GIcA, P-D-X~I,P-D-GalA, a-L-Rha, P-D-G~cNAc a. Anti-, a-and P-D-Glucose Antibodies.-Glucose is the most abundant carbohydrate in nature and occurs in free form or as a constituent of oligosaccharides, polysaccharides, glycoproteins, glycolipids, and glyco-

JOHN H. PAZUR

214

sides. Antibodies with specificity for glucose can be useful in many ways. Anti-glucose antibodies with specificity for both anomers of glucose have now been isolated from the immune serum from rabbits immunized with glycoconjugates of a-D-glucose (Glc) and bovine serum albumin (BSA) or P-D-G~cand BSA.37The subcutaneous immunization procedure described in Section IV was followed. The a and p forms of the glycoconjugates are synthesized from the aminophenyl glycosides and BSA by the carbodiimide method. The structural formula for the p-aminophenyl a-D-glucosyl-BSA conjugate used in the immunization is shown in (1) and the corresponding /3-glycoconjugate contained the /3 anomer of glucose. In both types of immune sera obtained from rabbits, anti-glucose antibodies were present. A small amount of anti-BSA antibody was also detected in the sera, but it could be separated from the anomeric forms of anti-glucose antibodies by affinity chromatography on Sepharose with ligands of a-D-glucose or pD-glucose. The affinity charts are reproduced in Fig. 6. The insets show agar-diffusion results with the purified antibodies. The specificity of the antibodies is further shown by the results of agar-diffusion tests, for which the plates are reproduced in Fig. 7, A and B. The agar-diffusion results in plate B also show that the protein carrier does not affect the antibody reactivity, as the same results were obtained with the glucose conjugates containing BSA or horse globulin moieties. Plates C and D of Fig. 7 also show that both types of anti-glucose antibodies react only with goat antirabbit IgG antibodies and are of the IgG class. No reaction occurred with antibodies of IgA or IgM types. The specificity of the antibodies was also verified by hapten-inhibition tests, the results of which are shown in Fig. 8. In these tests decreasing amounts of antigen were used with the pure antibodies and with antibodies that had been treated with potential inhibitors for 2 h. Agar diffusion was used to observe the rate of formation of precipitin bands with the various amounts of antigen. A comparison of the amount of antigen required to

CH,OH

I

OH 1

ANTI-CARBOHYDRATE ANTIBODIES

0

20

40 60 ELUTION V O L U M E (mL)

215

80

FIG.6.-Affinity-~hromatography elution patterns for the (Y-D- and P-o-anti-glucose antibodies; A = a-D-glucose-Sepharose 4B column, B = P-D-glucose-Sepharose 4B column, aG = methyl a-o-glucopyranoside, and P-G = methyl P-D-ghcopyranoside. Insets are agardiffusion patterns for the purified antibodies .( or P ) against a-or P-o-glucose-BSA.

give the same amount of precipitin complex with the native and with the antibody samples treated with inhibitor permits estimation of the percentage of inhibition. Methyl a-D-glucopyranoside gave high inhibition (80%) of a-glucose antibodies, whereas the methyl P-glucoside did not inhibit precipitin formation. With the P-glucose antibody methyl P-glucoside gave (55%) inhibition of the precipitin reaction, but the methyl a-glucoside derivative did not inhibit this reaction. The molecular size and molecular homogeneity of the two types of antibodies were determined by the sucrose density-gradient ultracentrifugation method.’* The sedimentation rates and the molecular weights of both types of antibodies were determined. The molecular weights were calculated using glucose oxidase as a standard34with an empirical formula,3’ and were 1.5 X lo5 for both antibodies. Electrophoresis and electrofocusing, coupled with agar diffusion, were devised to further characterize the antibodies. The results are presented in Fig. 9. Whereas the antibodies yield single bands on electrophoresis, multiple bands were obtained on electrofocusing. The latter results show that the preparations contain multimolecular proteins. The proteins form

JOHN H. PAZUR

216

C

D

FIG.7.-Agar-diffusion patterns of anti-glucose antibodies with various glycoconjugates (A and B) and immunoglobulin antibodies (C and D): M = mixture of the two antibodies, a! = antibodies specific for a-Glc-BSA, P = antibodies specific for P-Glc-BSA, 1 = a-GlcBSA, 2 = 0-Glc-BSA, 3 = a!-Glc-horse globulin, 4 = P-Glc horse globulin, A = goat antirabbit IgA antibodies, G = goat anti-rabbit IgG antibodies, and M = goat anti-rabbit IgM antibodies. [Reprinted with permission from J. H. Pazur, F. J. Miskiel, N. T. Marchetti, and H. R. Shiels, Pharm. Pharmacol. Letr., 2 (1993) 232-235.1

FIG.8.-Hapten inhibition of anti-glucose antibodies. A, B, C = a antibodies and D, E, F = /3 antibodies by methyl a-o-glucopyranoside or methyl P-o-glucopyranoside. Wells 1-6 contain decreasing concentration of a-glucosyl-BSA and wells 7-12 contain decreasing concentration of P-glucosyl-BSA. Wells not numbered contain the same concentration of antigen as in the plates horizontally adjacent.

ANTI-CARBOHYDRATE ANTIBODIES

217

FIG. 9.--Gel electrophoresis (A) and isoelectric focusing (B) of anti-glucose antibodies. = a serum, A, = a antibodies, Sz = p serum, A2 = P-antibodies, P = precipitin band, T = solution of P-Glc-BSA. S,

a unique set of antibodies, with each member forming a precipitin complex with the antigen. In the early immunology literature”,” reports on the detection of antiglucose antibodies in immune serum obtained from rabbits immunized with glycoconjugates of glucose and bovine serum albumin of different types have appeared. Glucose-containing oligosaccharides have also been coupled to protein, and such glycoconjugates have been used to produce anticarbohydrate However the anti-glucose antibodies observed in the earlier studies were not purified and many of the properties of these antibodies were not determined.

b. Anti-P-D-GalactoseAntibodies.-A ~-D-galactosyl-bovine serum albumin conjugate (2) was made available by Dr. David Bundle. It had been synthesized by coupling 8-ethoxycarbonyloetyl P-D-galactopyranoside to bovine serum albumin.” The conjugate (0.2% solution) was mixed with an

JOHN H. PAZUR

218

CH,OH

I

OH

equal volume of complete Freund's adjuvant and used to immunize rabbits subcutaneously at multiple sites in the back of the neck weekly for 8 weeks?" After the fourth week, blood samples were drawn and serum prepared in the conventional manner. The serum is subjected to affinity chromatography on P-D-galactosylSepharose synthesized from p-aminophenyl P-D-galactopyranoside and CNBr-activated Sepharose. After adsorption of the serum, the column of adsorbent is washed with phosphate buffer of pH 7 and non-antibody protein is removed. Next the column is washed with 0.5 M D-galactose solution and the UV-absorbing material is eluted from the column. This material was shown to be anti-galactose antibodies by agar-diffusion tests. In Fig. 10, plate A, are shown agar-diffusion results with the anti-galactose antibodies with BSA, periodate-oxidized conjugates, and the conjugates. Plate B of the figure shows antibodies with BSA, periodate-oxidized conjugates, and the conjugates. Plate B of the figure shows agar-diffusion results with anti-BSA antibodies with the same compounds. It maybe noted that the new UV-detectable material reacts with galactosyl BSA to yield a strong precipitin band (plate A). No precipitin was formed by the UV-absorbing material with BSA or periodate-oxidized Gal-BSA. Plate B shows that anti-BSA antibodies reacted with BSA, oxidized Gal-BSA, and Gal-BSA. Therefore, the BSA moiety does not contribute to an appreciable extent toward synthesis of antibodies specific for the glycoconjugate of galactose and BSA. The immunodeterminant group of the conjugate is the galactose moiety, which activates the immune system to produce anti-galactose antibodies. Inhibition tests confirm this conclusion, since the galactose is an inhibitor of the precipitin reaction of the antibodies with the Gal BSA (D of Fig. 10). To determine the nature of monosaccharide residues in an anticarbohydrate antibody, a sample of 2 mg of anti-Gal antibodies is hydrolyzed in 0.2 mL of 0.2 M HCl by heating in a boiling water-bath for 2 h.

ANTI-CARBOHYDRATE ANTIBODIES

219

FIG. 10.-Reactivity of anti-galactose antibodies (well A , ) and anti-BSA antibodies (well A2) with BSA ( I ) , periodate-oxidized P-Gal-BSA (2). and P-Gal-BSA ( 3 ) . Inhibition of anti-galactose antibodies (Ab) by galactose (D) and glucose (E), and reference (C). Wells 4-7 contain decreasing amounts of P-Gal-BSA. (Reprinted from Journal of Immunological Methods, Volume 75, J. H. Pazur and S. A. Kelly, pp. 107-116, copyright 1984 with kind permission of Elsevier Science-NL, Sara Burgerhartstraat 25, 1055 KV Amsterdam, The Netherlands.)

The hydrolyzate and reference carbohydrates (fucose, mannose, galactose, glucosamine, galactosamine, and neuraminic acid) are subjected to paper chromatography in the n-butyl alcohol-pyridine-water solvents-system.’8 One chromatogram is stained with silver nitrate reagent,56another chromatogram is sprayed with galactose oxidase?’ and a third chromatogram is stained for hexose amines.58A fourth chromatogram is treated with reagents for neuraminic acid.’9 A photograph of the chromatograph stained with silver nitrate is reproduced in Fig. 11. The hydrolyzate evidently contained fucose, mannose, galactose, glucosamine, galactosamine, and neuraminic acid. These sugar residues were present in the antibody molecule. The last four compounds were also identified by the reagents specific for each of the compounds. c. Anti-cY-r,-Mannose Antibodies.-To prepare anti-mannose antibodies, experimental rabbits are immunized with a vaccine of equal parts of 2% of a-D-mannosyl-bovine serum albumin in saline and Freund’s complete adjuvant.6‘)The immunization is performed by the subcutaneous method weekly with 1 mL of vaccine. The period of immunization is 15 weeks. Blood samples are collected after 5 weeks of immunization and used to

220

FIG.11 .-Carbohydrate

JOHN H. PAZUR

constituents in acid hydrolyzate of anti-a-galactose antibodies.

prepare immune serum from which antibodies are isolated by affinity chromatography on a-D-mannosyl-Sepharose. The latter is prepared by coupling p-aminophenyl a-D-mannopyranoside to cyanogen bromide-activated Sepharose 4B, following the directions in Section 111. Diffusion in agar performed by the conventional method shows a strong reaction between the antibody and Man-BSA, but not with BSA (Fig. 12, plates A). However, both compounds give precipitin complex with antiBSA serum. Oxidation of the antigens with periodate no longer gives a precipitin reaction with the anti-mannose antibodies, but has no effect on the anti-BSA antibodies. Hapten-inhibition results are also shown in Fig. 12, plates C and D. These tests are conducted with the purified antibody

FIG.12.-Reactivity of anti-a-mannose antibodies and anti-BSA antibodies with the native and periodate-oxidized mannose-glycoconjugate and BSA (plates A and B). M = Man-BSA. xM = periodate-oxidized Man-BSA, B = BSA, xB = periodate-oxidized BSA, A = antimannose antibodies, A? = anti-BSA antibodies. Plates C and D show hapten inhibition of purified anti-mannose antibodies (A,) with mannose (I,). The amount of antigen in the outer wells ranges from 20 pg in well 1 to 1 pg in well 6. [Reprinted with permission from J. H. Pazur. B. Liu. and T. Witham. J. Protein Chem., 13 (1994) 59-66.]

ANTI-CARBOHYDRATE ANTIBODIES

221

sample and a sample which has been preincubated with mannose. The samples are tested with decreasing amounts (wells 1 to 6 ) of the Man-BSA by agar diffusion. The mannose digest gives a precipitin complex visible only at the highest concentration of antigen, whereas the control yields precipitin bands at four concentrations of antigen. These results show that a-D-mannose combines with the active site of the antibody and strongly inhibits precipitin formation with the antigen. d. Anti-1-Thio-a-D-Mannose Antibodies.-The glycoconjugate (3) of 1thio-a-Man and BSA was prepared from cyanomethyl 1-thio-a-Dmannopyranoside and BSA following the procedure previously described by Lee et al." The glycoconjugate was used to immunize rabbits with a vaccine prepared from equal amounts of the glycoconjugate and complete Freund's adjuvant by using the multisite subcutaneous method.62This conjugate induced the synthesis of antibodies in the host, namely anti-Man-Santibodies and some anti-BSA antibodies, as shown by the results on diffusion plate A of Fig. 13. The anti-thio-Man antibodies were isolated by affinity chromatography on a column of Sepharose 4B bearing 1-thio-Dmannose ligands. The inhibition of precipitin formation by 1-thio-D-mannose and derivatives is shown in the results recorded in Plates C, D, E, and F of Fig. 13. The sulfur derivatives, p-nitrophenyl 1-thio-D-mannopyranoside(well 1,) and ethyl 1-thio-D-mannopyranoside (well 13), caused a marked decrease in the amount of precipitin formation, in comparison to that obtained with the native antibodies (Well Al). However, mannose did not decrease the amount of precipitin formation (well 12). This compound did not bind to the combining site of the antibody. Apparently, the thio group at position 1 of the mannose is required for the binding to occur. That the 1-thio-D-mannopyranose residue of the antigen is the immunodeterminant group was verified by the results of the oxidation of the antigen by peroxypropanoic acid and by diffusion testing (plate B of Fig. 13). The

CH,OH

I

3

222

JOHN H. PAZUR

FIG.13.-A: Agar diffusion of immune sera (Se), 1-thio-o-mannose antibodies (A,), and anti-BSA antibodies (A2) against Man-S-BSA (I) and BSA (2). B: Agar-diffusion plate of anti-Man-S-antibodies and antibodies oxidized by peroxypropanoic acid for 0, 4,and 8 h. C, D, E, and F Hapten inhibition by agar diffusion, A, = purified anti-Man4 antibodies: I, = antibodies + p-nitrophenyl I-thio-a-o-mannopyranoside; I2 = antibodies + o-mannose; I3 = antibodies + ethyl 1-thio-a-o-mannoside; 1 to 6, outer wells contain decreasing concentration of Man-S-BSA. (Reprinted with permission from Journal of Protein Chemistry, Volume 9, J. H. Pazur, B. Liu, Nan Q Li, and Y. C. Lee, pp. 143-150, copyright 1990 Joiirnal of Protein Chemistry.)

antigenicity of the glycoconjugate was destroyed rapidly on oxidation by peroxypropanoic acid oxidation. It was barely detectable at 4 h and was completely abolished after 8 h of oxidation. These results establish the essentiality of the 1-thio group for precipitin formation. e. Anti-a-L-Fucose and Anti-BSA Antibodies.-The rabbits used in immunization with fucosyl-BSA responded with the production of two sets of antibodies; one set is anti-fucose and the other is anti-BSA The sets were separated by affinity chromatography on two Sepharose columns, one with fucose ligands and the other with BSA ligands. The first adsorbent was synthesized from p-aminophenyl a-L-fucoside and cyanogen bromide-activated Sepharose 4B, and the second using BSA in place of the glycoside. The antibodies were separated by affinity chromatography on the two columns connected serially and containing first the adsorbent with ligands of L-fucose and second the adsorbent with ligands of BSA.

ANTI-CARBOHYDRATE ANTIBODIES

223

The anti-fucose antibodies were eluted by 0.5 M L-fucose solution from the first column and the anti-BSA antibodies by elution with 0.5 M ammonium thiocyanate from the second. Agar diffusions are shown in the plates in Fig. 14. On gel electrophoresis, the purified antibody preparations yield single bands when the gel is stained for proteins. However, on gel isoelectrofocusing, differences in the results maybe noted, as shown in Fig. 15. Several protein isomers were present in each antibody preparation, with 7 isomers being detected in the anti-BSA antibodies (B) and 11 isomers in the antifucose antibodies (F). The coupled electrofocusing-agar diffusion method showed that each isomer of the anti-fucose set possessed the same antibody activity with the antigen, a-L-fucosyl-BSA. Fucose was tested as an inhibitor for both types of antibodies by the micro-inhibition test. These results are presented in Fig. 16. The center well of plate A contains native anti-fucose antibodies, with the native antibodies diffusing against decreasing concentrations (20 to 1 pg) of FucBSA in the outer wells (1 to 6). The anti-fucose antibody yielded precipitin bands with 4 concentrations of antigen. Antibodies incubated with L-fucose (plate B) yielded a precipitin complex only at the highest concentration of antigen. A calculation from the concentrations shows that the L-fucose

FIG. 14.-Agar-diffusion plates of anti-fucose antibodies and anti-BSA antibodies. F = fucose-BSA. B = BSA, xf, xB = periodate-oxidized samples, Se = anti-BSA antibodies, and A, = anti-fucose antibodies. (Reprinted with permission from Journal of Protein Chemistry, Volume 13, J. H. Pazur, B. Liu, and T. F. Witham, pp. 59-66, copyright 1994 Journal of Protein Chemistry.)

224

JOHN H. PAZUR

FIG.15.--Gel electrofocusing of anti-fucose and anti-BSA antibodies; gel B = anti-BSA antibodies, gel F = anti-fucose antibodies; gel E = embedded gel of anti-fucose antibodies; P = precipitin band, and T = solution of fucose-BSA. (Reprinted with permission from Journal of Protein Chemistry, Volume 13, J. H. Pazur, B. Liu, and T. F. Witham, pp. 59-66, copyright 1994 Journal of Protein Chemistry.)

inhibited about 85% of the antibody. Plates C and D of Fig. 16 show the inhibition results with the anti-BSA antibodies, control (Plate C), and with L-fucose inhibitor (plate D). These antibodies gave precipitin bands at four concentrations of the glycoconjugate. Thus, the L-fucose did not inhibit the anti-BSA antibodies, but did inhibit the anti-fucose antibodies. Results of the density-gradient centrifugation shown in Fig. 4 revealed that the anti-Fuc antibodies yielded a single symmetrical peak. Calculations from sedimentation data using an empirical formula yielded molecularweight values of 1.5 X 10’ for the antibody preparation. The molecular weight is in agreement with the molecular weight of other anticarbohydrate antibodies.

FIG.16.--lnhibition of anti-Fuc and anti-BSA antibodies by fucose. A, = anti-fucose antibodies, 1, = anti-fucose antibodies + fucose, A2 = BSA antibodies, 1, = BSA antibodies + fucose.

ANTI-CARBOHYDRATE ANTIBODIES

-3 ) - 6-deoxy

- L-

Tal - ( I

-

3) - D-Gal - ( I -3)-

L - Rha -( 1

4

+

2)- L - Rha - ( I

225

-

I

I D - GlcA 4

f. Anti-Glucuronic Acid Antibodies.-The immunogenic carbohydrate in the cell wall of Streptococcus bovis that induces the synthesis of antibodies is a tetraheteropolysaccharide composed of 6-deoxy-~-talose,L-rhamnose, D-galactose, and D-glucuronic acid. The structure of a repeating unit of the polysaccharide is shown in 4. This structure was deduced from methylation analyses, borohydride reduction, and alkali elimination results. Two types of anti-carbohydrate antibodies have also been induced by the polysaccharide and are present in sera of rabbits immunized with a vaccine of nonviable cells of S. b o v i ~One . ~ ~such antibody type are anti-GlcA antibodies directed against terminal D-glucuronic acid units of the polysaccharide and purified by chromatography on a glucosyluronic-Sepharose 4B column. The other type is anti-GlcA-Rha antibodies directed at oligosaccharide units of glucuronic acid and rhamnose. The second type of antibody has also been purified and is discussed later in the section on oligosaccharides. Immunodiffusion in agar was performed by a standard procedure with the immune serum and anti-GlcA and anti-GlcA-Rha antibodies directed against the native and a modified polysaccharide in which the glucuronic acid units residues have been reduced. The results are presented in Fig. 17. The anti-GlcA antibodies are of the IgG class of immunoglobulins and possess molecular weights of 1.5 X lo5. Isoelectrofocusing results showed that the anti-GlcA isoantibodies consist of four isomeric proteins

FIG.17.-Agar-diffusion patterns for the native polysaccharide of Streptococcus bovis (1) and the polysaccharide (2) having reduced D-glucuronic acid with antiserum (S), with antiGlcA antibodies (A,), and with anti-GlcA-Rha antibodies (A*). [From J. H. Pazur, K. L. Dreher. R. L. Kubrick. and M. S. Erikson, Anal. Biochem., 126 (1982) 285-294.1

226

JOHN H. PAZUR

(gel 1 of Fig. 18). The anti-GlcA-Rha isoantibodies consist of 11 isomeric proteins (gel 3 of Fig. 18). Gel 2 in the figure shows the pattern for the original mixture of the two types of antibodies and 15 isomeric proteins. g. Anti-P-D-Xylose Antibodies.-A mixture of polysaccharides from flaxseed4’ has been prepared and used to immunize a single rabbit, and two types of antibodies have been obtained. One type is specific for terminal D-xylose and the other is specific for terminal D-galacturonic acid units of the polysaccharides. The vaccine was a suspension of flaxseed polysaccharides (2% solution) and Freund’s complete adjuvant in equal proportions. The immunization was performed weekly for 7 weeks subcutaneously (1 mL) at multi-sites in the neck and back of the rabbit. Blood samples were drawn in the fourth and subsequent weeks. Serum was prepared from each blood sample by a standard method. The antibodies were isolated from the serum by affinity chromatography on two types of Sepharosebased adsorbents, one with ligands of xylose and the other with ligands of polysaccharides from flaxseed.65The elution of the antibodies from the adsorbent bearing xylose ligands was performed with 0.5 M D-xylose solution, and elution from the other adsorbent was with galacturonic acid (Fig. 19). In structural studies, flaxseed polysaccharides were separated into neutral and acidic fractions by use of cetyldimethylammonium bromide. Data from methylation analys@ showed that the first fraction yielded only methylated D-xylose derivatives, with a high amount of 2,3,4-tri-0-methyl-~-xylose

1

2

3

FIG.18.-Isoelectrofocusing gels of anti-GlcA antibodies (l), anti-GlcA-Rha antibodies (3). and a mixture of the two types of antibodies (2). [From J. H. Pazur, K. L. Dreher, R. L. Kubrick, and M. S. Erikson, Anal. Biochern., 126 (1982) 285-294.1

oezv

I

W

=

0

A

3

>

3

c

2 0 c

-I

4

228

JOHN H. PAZUR

derived from terminal D-xylose units of the polysaccharide. The antibodies eluted with xylose were shown, by adsorption and elution from a xylose affinity column, agar diffusion, and hapten inhibition ( A and B of Fig. 20), to be anti-xylose antibodies.

h. Anti-Galacturonic Acid Antibodies.-The acidic polysaccharide from flaxseed is composed of L-rhamnose, L-fucose, L-galactose, and Dgalacturonic acid. On reduction and methylation, a high amount of 2,3,4,6tetra-0-methyl-D-galactose derived from D-galacturonic acid units of the polysaccharide was obtained. An affinity adsorbent was prepared from AHSepharose 4B and flaxseed polysaccharide and was used to isolate antigalacturonic acid antibodies from the immune serum (Fig. 19). Agar diffusion and inhibition results for the galacturonic acid antibodies are reproduced in Fig. 20 C and D. The precipitin bands in Fig. 20 C are not as intense as in Fig. 20 A, and the second band between wells S and Ag is missing because the photograph was taken after a short diffusion time. The preparation of anti-D-xylose and anti-D-galacturonic acid antibodies has been achieved for the first time.

FIG.20.-Agar diffusion and inhibition of antibodies specific for D - X ~ ~ Ounits S ~ (A and B) and specific for o-galacturonic acid (C and D).

ANTI-CARBOHYDRATE ANTIBODIES

229

i. Anti-Rhamnose Antibodies.-L-Rhamnose (6-deoxy-~-mannose)is a constituent carbohydrate of some microbial immunogenic heteropolysaccharides. This deoxy sugar often functions as the immunodeterminant group of the immunogens. Anti-rhamnose antibodies have now been isolated from serum of rabbits immunized with vaccine of Streptococcus mutuns, KI-R.*' A vaccine of nonviable cells and Freund's complete adjuvant was used for immunization. Serum containing anti-rhamnose antibodies has been shown to be effective in controlling some types of oral microorganisms that cause p l a q ~ e . ~The ' antibodies were isolated by affinity chromatography. The affinity adsorbent used to isolate the anti-rhamnose antibodies was prepared by the coupling reaction from p-aminophenyl a-L-rhamnopyranoside and cyanogen bromide-activated Sepharose 4B. The final adsorbent was transferred to a column (20 cm X 1 cm), washed thoroughly with 0.02 M phosphate buffer of pH 7 in saline, and used for affinity chromatography and purification of the anti-rhamnose antibodies. The affinity pattern and the agar diffusion of anti-Rha antibodies against the polysaccharide are shown in the inset of Fig. 1.

j. Anti-N-Acetyl @-D-Glucosamine.-The group A Streptococcus is the chief pathogenic group of the streptococcal microorganisms. Among the diseases for which this group may be a causative agent are scarlet fever, endocarditis, erysipelas, puerperal fever, and rheumatic fever.68The immunology of S. pyogenes has been studied most extensively, and early work in this area was done by investigators at the Rockefeller U n i ~ e r s i t yThe .~~ investigations have led to formulation of methods for the detection of these pathogens in infectious diseases. The polysaccharide in the cell wall of group A strains consists of rhamnose and N-acetylglucosamine.7nThe most recent structure proposed for the repeating unit of this polysaccharide is shown" in 5. The isolation of the antibodies was effected by affinity chromatography from immune serum obtained from rabbits immunized with nonviable cells of S. pyogenes. The serum was provided by Dr. M. McCarty of Rockefeller University. The adsorbent used for the isolation of the antibodies

-3 ) -

L - Rha-( 1-2)- L - Rha - ( I

- + 3 ) -- Rha ~ -(I

3

T I

p - GlcNAc 5

-

JOHN H. PAZUR

230

-IJ

Serum protein

N

<

I

0

I

1s

Al

I

45

ELUTION

b

5:

do

I

105

I

120

VOLUME tmLJ

FIG.21 .-Purification of anti-group A streptococcal antibodies by affinity chromatography. Inset is agar-diffusion pattern.

was synthesized from CNBr-activated Sepharose and p-aminophenyl 2acetamido-2-deoxy-cu-~-glucopyranoside by the method described in Section IV. The affinity chromatography pattern is reproduced in Fig. 21. The UV-absorbing material which eluted with N-acetylglucosamine was collected and concentrated. Agar diffusion showed that the sample yielded a precipitin band with the polysaccharide from the cell wall of S. pyogenes (inset of Fig. 21). The constituent units of this polysaccharide are GlcNAc and Rha, and these monosaccharides were tested as hapten inhibitors. The results are shown in Fig. 22. It may be seen that GlcNAc (I,) is an inhibitor but, in comparison to the control with no inhibitor (Ab), the Rha (Iz) was not. Results in Fig. 22 establish that the determinant group of the antigen is GlcNAc and not Rha. On isoelectrofocusing and coupled diffusion, the antibody preparation was shown to consist of 10 isoantibodies, and each member possessed anti-GlcNAc activity.

FIG.22.-Inhibition of anti-GlcNAc antibodies (Ab) by GlcNAc (11) and Rha (12). (Reprinted from Journal of Immunological Methods, Volume 75, J. H. Pazur and S. A. Kelly, pp. 107-116, copyright 1984 with kind permission of Elsevier Science-NL, Sara Burgerhartstraat 25, 1055 KV Amsterdam, The Netherlands.)

ANTI-CARBOHYDRATE ANTIBODIES

231

2. Specificity for Oligosaccharides: f?-D-Gal-(l+ ~)-D-GIc,~w-D-GIc(1 + 6)-~-Glc(Myeloma), p - ~ - G l c A - ( l +3)-~-Gal(Gum Arabic), P-L-Ara-(l+ 4)-~-GlcA(Gum Arabic), 4,6-Pyruvate-~-Man-(l+4)D-GkA (Xanthan), Man, (Glucoamylase), Fuc,-(Tumor)

a. Anti-Lactose Antibodies.-The anti-lactose antibodies were prepared by use of a cell-wall polysaccharide from Streptococcus fuecuh Strain N. The molecular structure of the polysaccharide has been determined by a combined analytical scheme of methylation and mass spectrometry, periodate oxidation, enzyme hydrolysis, and acetolysis.’* The polysaccharide is composed of a pentasaccharide repeating unit of glucose (1 ---* 4)-glucose(1 + 4)-galactose with lactose side chains attached to position 6 of the second glucose unit. The diagrammatic structure for the repeating unit is shown by 6. Nonviable cells of S. fuecalis strain N were used for the immunization of rabbits to activate the immune system to synthesize antibodies. To prepare the vaccine, the cells from 500 mL of freshly grown culture were collected by centrifugation at 10,OOO rpm and then shaken in 100 mL of 0.2% formaldehyde in saline for 48 h. After removal of the formaldehyde by washing the cells with 0.01 M phosphate buffer of pH 7.2 in saline, the cells were suspended in 80 mL of sterile saline. Viability tests showed that the cells were made nonviable by this treatment. This suspension exhibited high absorbance at 600 nm and was used for immunizing rabbits. Four rabbits were immunized each with 0.3 mL of the nonviable suspension of cells administered daily intravenously for 3 days, followed by a rest period of 4 days. This schedule was repeated for 5 weeks. After a 1-week rest period, a second administration of vaccine was used following the foregoing schedule. Blood samples were drawn weekly and serum was obtained. In -6 weeks the sera of the rabbits showed a high titer of antibodies directed at the cell-wall polysaccharide. The antisera from each rabbit were maintained separately. The antibodies were isolated from the serum by an affinity-chromatography procedure employing adsorbtion on lactosyl-

232

JOHN H. PAZUR

Sepharose and elution with lactose (Fig. 23). The UV-absorbing fraction that was eluted with the lactose solution was collected and the protein precipitated by addition of an equal volume of saturated ammonium sulfate. On refrigeration of the sample overnight, a white precipitate formed. This precipitate was collected by centrifugation and redissolved in 0.2 mL of 0.02 M phosphate buffer of pH 7 in saline. The agar-diffusion test shown in the inset of Fig. 23 showed that high-titer antibodies were produced that formed a precipitin complex with the antigen. Several affinity runs were made. The antibody samples were combined and lyophilized. The yield of anti-lactose antibody was 50 mg from 20 mL of serum. A sample of the antibody preparation was used for quantitative precipitin f~rmation,’~using the phenol reagent to measure protein concentration^.^^ Inhibitions were done with lactose, galactose, and glucose, structural units of the antigen,15 and their methyl glycosides. The results are shown in Fig. 24, diagram A. Lactose and derivatives were strong inhibitors of the precipitin reaction. Also shown in Fig. 24, diagram B, are results of densitygradient centrifugation of the antibody and the light and heavy chains. The latter are discussed later in this section. Gel electrophoresis was performed in barbital buffe?’ of pH 8.3, and gel isoelectrofocusing was performed in ampholine-sucrose solution of pH 5 to 8 gradient.” Gels were removed from the apparatus at completion of

FIG.23.-Affinity chromatography of immune serum produced by immunization of a rabbit with nonviable cells of S.faecalis. Inset is the agar diffusion of antibodies and lactosyl polysaccharide from the same organism. (Reprinted with permission from Journal of Protein Chemistry, Volume 6. J. H. Pazur. M. E. Tay, B. A. Pazur, and F. J. Miskiel, pp. 387-399, copyright 1987 Journal of Protein Chemistry.)

1

Ab

Tz

---------lm,U

-

H

-G+-

0

n

\-/L ,'

r 0

1

3

2

4

CONCENTRATION OF INHIBITOR (mM)

A

5

0

23,aOo

\

I

I

1

2

, v I

3 D I S T A N C E Icm.1

I

I

4

5

B

FIG. 24.-A: Hapten inhibition of the anti-lactose antibodies by lactose and galactose and derivatives. B: Dissociation of anti-lactose antibodies into light and heavy chains followed by density-gradient centrifugation. (A. Reprinted with permission from Jozirnal of Biological Chemistry, Volume 253, J. H. Pazur. K.L. Dreher, and L. S. Forsberg, pp. 1832-1837, copyright 1978 Jourizal of Biological Chemistry: B. Reprinted with permission from Journal of Protein Chemistry. Volume 6. J. H. Pazur. M. E. Tay, B. A. Pazur. and F. J. Miskiel, pp. 387-399, copyright 1987 Joiirnnl of Prorein Chemistry.)

234

JOHN H. PAZUR

the run and stained with a solution of 0.02% Coomassie Brilliant Blue G250 in 12.5% trichloracetic acid for 1 h at 37°C. The gels were destained with 7% acetic acid until the background was clear. The results show that the purified antibody contained multimolecular protein species (Fig. 25). The electrofocusing resolved the proteins into individual components. Each protein possesses anti-lactose activity and is therefore an isoantibody. This conclusion is based on the presence of precipitin complex opposite all protein bands in Fig. 25. The mixture of antibodies was subjected to dissociation into light and heavy chains. The details of a method for preparing the light and heavy chains from y-immunoglobulins have been outlined by Edelman and coworker~,’~and this method was used. A sample of 20 mg of anti-lactose antibodies, dissolved in 1 mL of 0.02 M phosphate buffer of pH 7.0, was dialyzed for 48 h at 4°C against multiple changes of 0.15 M Tris buffer of pH 8.2 containing 0.15 M NaCl and 0.004 M EDTA. The antibody solution was then mixed with an equal volume of 0.01 M solution of 1A-dithiothreitol in 0.1 M Tris buffer of pH 8.2 and kept for 2 h at room temperature. At this point the mixture was stirred with 5 mL of 0.12 M iodoacetamide in the pH 8.2 buffer for 15 min at 4°C. During this period, the pH of the solution was maintained at 8.2 by addition of M Tris buffer as needed.

Fic. 25.--Gel electrophoresis and isoelectrofocusing of anti-lactose antibodies followed by agar diffusion. A, electrophoresis: gel 1 stained with Coomassie Blue, gel 2 embedded in agar, area of precipitin formation (3), and solution of antigen (4). B, electrofocusing gel patterns (5-8) similar to series (14).

ANTI-CARBOHYDRATE ANTIBODIES

235

Finally, the reduced and alkylated antibodies were dialyzed against M propanoic acid at 4°C overnight. The sample was then fractionated by chromatography on Sephadex G-100 with 0.5 M propanoic acid as the eluting solvent. Forty fractions of 5 mL were collected from the column and the UV-absorbing fractions located by absorbance measurements. Three peaks of UV-absorbing compounds were obtained; located in fractions 12-15 (native antibodies), fractions 17-21 (heavy chains), and fractions 24-31 (light chains). The latter two groups of fractions were combined separately, dialyzed against distilled water for 24 h, and then taken to dryness by lyophilization. The amount of heavy chains (fractions 17-21) obtained was 8 mg and of light chains (fractions 24-31) 6 mg. An undissociated antibody, the light-chain and heavy-chain preparations were subjected to density-gradient ultracentrifugation. The results are shown in Fig. 24B. The fractions and native antibodies were subjected to density-gradient centrifugation. From the centrifugation rate and an empirical f ~ r m u l a 'the ~ molecular weight of the antibody was calculated to be 1.5 X lo". The molecular weights of light and heavy chains were calculated to be 23,600 and 51,400, respectively. The individual anti-Lac isoantibodies were isolated in pure form by the liquid isoelectrofocusing method.76 A sucrose-stabilized gradient of ampholine (pH 6 to 8) was used as the liquid column. The gradient solution (110 mL) was funneled into the apparatus and prefocused for 24 h at 800 V. A sample of 10 mg of the anti-lactose antibodies was then introduced into the gradient column. Additional isoelectrofocusing was continued at 800 V for 65 h. At the end of this time the gradient was fractionated in 1-mL fractions and the UV absorbance of each fraction was measured at 280 nm. The data are plotted in Fig. 26A. Gel electrophoresis was performed on the fractions by the method of Davis.29A photograph of the results is reproduced in Fig. 26B. That the pure isoantibodies retained antibody activity is shown in Fig. 27 by the coupled electrophoresis-agar diffusion method. The results for two isoantibodies (4 and lo), which show antibody activity, are reproduced in A and B of Fig. 27. Dissociation of the individual isoantibodies (6 to 10) was conducted by the method already outlined. However, the final reaction mixtures of the individual isoantibodies were not alkylated, but were subjected immediately to gel electrophoresis in Tris buffer of pH 8.3 containing sodium dodecyl sulfate and 2-mercaptoethanol. The results of electrophoresis of the isoantibodies (6,7,8,9, and 10) and references are shown in C of Fig. 27. It may be noted in the figure that each homogeneous isoantibody dissociated into a single light and a single heavy chain. The antibodies were not assembled from a pool of heterogenous chains.77

236

JOHN H. PAZUR

FIG. 26.-A: Liquid isoelectrofocusing pattern in a gradient of pH 6-8 for anti-lactose isoantibodies. B: Gel electrophoresis of anti-lactose isoantibodies. (Reprinted with permission from Journal of Protein Chemistry, Volume 6 , J . H. Pazur, M. E. Tay, B. A. Pazur, and F. J . Miskiel, pp. 387-399, copyright 1987 Joicrnal of Protein Chemistry.)

b. Anti-GlcA-Rha Antibodies.-These antibodies are present in immune serum produced by immunization of an experimental animal with the nonviable cells of Streptococcus bovis. For isolating GlcA-Rha antibodies, an adsorbent was prepared from AH Sepharose 4B and the tetraheteropolysaccharide, utilizing the carbodiimide reaction. A sample of 1.5 g of AH-Sepharose 4B was suspended in 6 mL of distilled water and then mixed with 50 pg of the polysaccharide. Next, 100 mg of 0-(carboxymethy1)cellulose (CMC) in 5 mL of water was added dropwise to the suspension. After reaction for 6 h at room temperature, the precipitate was recovered by filtration and washed with 0.5 M NaCl and with distilled water. The product was then treated with 10 mL of 0.2 M acetic acid in order to block unreacted

ANTI-CARBOHYDRATE ANTIBODIES

237

FIG.27.-A and B: Electrophoresis and agar diffusion of isoantibodies in gels 4 and 10 (of Fig. 26B). C Sodium dodecyl sulfate gel-electrophoretic patterns for the anti-lactose isoantibodies (Ab), light (L) and heavy (H) chains and dissociated isoantibodies (gels 6, 7, 8, 9, and 10 of Fig. 268). (Reprinted with permission from Journal of Protein Chemistry, Volume 6, J . H. Pazur. M. E. Tay, B. A. Pazur, and F. J. Miskiel, pp. 387-399, copyright 1987 Journal o f Protein Chemistry.)

groups. The final product was transferred to a glass column and used as an adsorbent for the anti-GlcA-Rha antibodies. The antibodies were present in the immune sera of a rabbit immunized with nonviable cells of S. bovis. Figure 17 shows that the serum contained antibodies which reacted with cell-wall polysaccharide of S. mutans (plate A) and also the anti-GlcA antibodies (plate B) and the anti-GlcA-Rha antibodies (plate C). Anti-glucosyluronate-rhamnose antibodies were isolated from the globulin fraction of serum devoid of the anti-GlcA antibodies. The latter were

238

JOHN H. PAZUR

removed by affinity chromatography on GlcA-Sepharose 4B and the globulin fraction was isolated from the unadsorbed protein eluate from this column. The y-globulin solution (1 mL) was introduced onto the column of polysaccharide AH-Sepharose 4B and the column was washed with 0.02 M phosphate buffer of pH 7 in saline until the nonadsorbed proteins were removed. The column was then washed with 20 mL of 1 M ammonium thiocyanate (NhSCN) in 0.02 M sodium phosphate buffer of pH 7, and UV-absorbing material was obtained. The results of agar diffusion tests are shown in Fig. 17. Both antibody preparations specific for GlcA and GlcA-Rha require GlcA to be reactive with the antigen. Neither of the preparations reacted with polysaccharide in which the glucuronic residues had been reduced. Quantitative precipitin tests were performed as de~cribed.'~ The amounts of precipitates obtained at the various concentrations were measured by the protein phenol method.74The inhibition values are recorded in Table I. These inhibition data show that the precipitin reaction between the tetraheteropolysaccharide and the anti-GlcA antibodies is strongly inhibited by Dglucuronic acid, but with the exception of galacturonic acid none of the other carbohydrates were inhibitory. The data in the table also show that the carbohydrates tested did not inhibit the precipitin reaction between the polysaccharide and anti-GlcA-Rha antibodies. The monosaccharides alone cannot completely fit the active site of this antibody to give a precipitin test. TABLE I Inhibition of the Precipitin Reaction of the Tetraheteroglycan and Rabbit Antiserum against S. bovb Carbohydrate

Concentration (mglmL)

GkA (Yo)

Inhibition

Inhibition GlcA-Rha (YO)

D-Glucuronic acid D-GlUCUrOfliC acid D-Ghcuronic acid D-GhCUrOfliC acid D-GalaCtOSe L-Rhamnose 6-Deoxy-L-talose" D-Glucose tone ~-Gh.1curono-6,3-lacl D-Glucuronarnide D-Mannuronic acid D-Galacturonic acid

0 20 40 80 40 40 a 40 40 40 40 40

0 56 82 93 8 0 0 5 3 6 9 13

0 ND 4 ND 6 2 0 5 ND ND ND ND

OThe test with this compound was performed by the capillary precipitin method. ND, not determined.

ANTI-CARBOHYDRATE ANTIBODIES

239

c. Anti-Isomaltose Myeloma Protein.-Myeloma protein reactive with carbohydrate in ascitic fluid from BALB/c mice bearing W3129 plasma cell tumors" was isolated by affinity ~hromatography.'~ This protein exhibits specificity for terminal isomaltose units of dextran, and accordingly isomaltosyl-Sepharose 4B was used for the isolation. The protein was eluted from the affinity column with a 2% solution of isomaltose. The protein had been used widely in studies on the nature of the antigen-antibody reaction.'" The adsorbent was prepared by coupling an isomaltose derivative with cyanogen bromide-activated Sepharose 4B. The derivative, p-aminophenyl a-isomaltoside, was synthesized enzymatically from maltose (0.2 g) and p-aminophenyl a-D-glucopyranoside (0.1 g) using a glucosyltransferase from Aspergillus niger." The reactants were mixed with 0.5 mL (14 units) of purified glucosyltransferase and enzyme action was allowed to proceed at room temperature for 24 h, at which point the enzyme was inactivated by heat. Examination of the inactivated digest by paper chromatography and spraying of the chromatogram with a periodate reagentx2 showed that aminophenyl oligosaccharide glycosides were produced. The first member of the series was p-aminophenyl a-isomaltoside, the second was paminophenyl a-isomaltotrioside, and so forth. The p-aminophenyl isomaltoside was isolated by preparative paper ~ h r o m a t o g r a p h yin~a~yield of 0.06 g. An affinity adsorbent was prepared from the p-aminophenyl cr-isomaltoside and CNBr-activated Sepharose 4B by reacting 0.03 g of the isomaltoside with 4 g of activated Sepharose 4B, following the procedure described in an earlier section. The final product was washed with 100 mL of 0.1 M acetate buffer of pH 4, followed by 100 mL of 0.1 M hydrogen-carbonate buffer of pH 8, and then transferred to a column (1.5 cm X 20 cm) and washed further with 0.02 M phosphate buffer of pH 7 in saline. The washed column was stored in a cold room until used to prepare the reactive protein. Isolation of the myeloma protein that combines with isomaltose units of dextran was achieved by affinity chromatography, for which the pattern is shown in Fig. 28. The eluate obtained with isomaltose was collected, dialyzed, and then lyophilized. Diffusion in agar, performed by standard methods, showed that the preparation formed a precipitin with dextran (inset of Fig. 28). Quantitative hapten inhibition tests were also perf~rmed.'~ The amount of myeloma protein-dextran complex that formed in individual tests was measured by the determination of protein in the precipitate, using a colorimetric method.74 The precipitin tests were performed in a final volume of 0.2 mL, which comprised 80 p L of 0.02 M phosphate buffer of pH 7, 20 p L of ascitic fluid or purified myeloma protein, and 100 p L of dextran B-1355s solution in phosphate buffer of pH 7. The extent to which glucose

JOHN H. PAZUR

240

FIG.28.-Affinity chromatography of myeloma protein on isomaltosyl-Sepharose. Inset of agar-diffusion plate. (Reprinted from Immunology Letters, Volume 5, J. H. Pazur, M. E. Tay, S. E. Rovnak, and B. A. Pazur, pp. 285-291, copyright 1982 with kind permission of Elsevier Science-NL, Sara Burgerhartstraat 25. 1055 KV Amsterdam, The Netherlands.)

derivatives inhibit the precipitin formation with myeloma protein and dextran is recorded in Table 11. Agar-diffusion tests were performed using dextran B-1355sand with the purified sample, the original ascitic fluid, and the nonadsorbed protein samples. The results of this experiment are shown in the plate of Fig. 29, along with gel-electrophoretic results. In the agar plate it may be noted that the purified myeloma protein (well 2), and the original ascitic fluid (well l), yielded intense precipitin bands with the dextran. These bands fused together, indicating identity in the two types of complex. However, the unadsorbed protein fraction (well 3) did not yield a precipitin band. The results in the photograph of the electrophoretic gels shown in Fig. 29 establish clearly that the myeloma protein has been removed from the ascitic fluid by the affinity chromatography procedure. Also, it should be TABLE I1 Percent Inhibition of Glucosyl Compounds for the Myeloma Protein and Precipitin Reaction Carbohydrate

Abbreviated Structure

Inhibition (%)

Glucose Maltose Nigerose lsomaltose lsomaltotriose

Glc a-Glc-(I + 4)-Glc a-Glc-(l + 3)-Glc a-Glc-(l + 6)-Glc a-Glc-(1 + 6)-a-Glc-( 1 + 6)-Glc

2 3 9 72 74

ANTI-CARBOHYDRATE ANTIBODIES

241

FIG.29.-GeI electrophoresis and agar diffusion of myeloma proteins. (Reprinted from Immunology Letters. Volume 5, J. H. Pazur, M. E. Tay, S. E. Rovnak, and B. A. Pazur, pp. 285-291, copyright 1982 with kind permission of Elsevier Science-NL, Sara Burgerhartstraat 25. 1055 KV Amsterdam, The Netherlands.)

noted in the figure (gel 2) that the purified myeloma protein consists of several protein species. To determine whether all of the isomeric myeloma proteins isolated do indeed combine with the dextran, a method utilizing isoelectrofocusingcoupled with agar diffusion was employed. The myeloma protein isomers did not separate well, but the results in Fig. 30 establish that all of the protein isomers react to give a precipitin with dextran.

Fic;. 30.-Gel electrofocusing of purified myeloma proteins. G = gel stained for protein: E = embedded gel: P = precipitin area: A = antigen solution. (Reprinted from Immunology Letrer.s, Volume 5. J. H. Pazur, M. E. Tay, S. E. Rovnak, and B. A. Pazur, pp. 285-291, copyright 1982 with kind permission of Elsevier Science-NL. Sara Burgerhartstraat 25.1055 KV Amsterdam, The Netherlands.)

242

JOHN H. PAZUR

d. Anti-Gum Arabic Antibodies.-Gum arabic is isolated from the gum exudate of semitropical shrubs, principally Acacia senegal. It is a polysaccharide of high molecular weight and unusual physical properties. Gum arabic contains four monosaccharide components, L-rhamnose, L-arabinose, Dgalactose, and D-glucuronic acid, connected by several types of glycosidic linkage^!^,^^^ A partial formula showing the antigenic groups is given in 7. Commercial gum arabic may be further purified by dissolving the powder in distilled water, separating the insoluble impurities by centrifugation, and removing the soluble, low-molecular-weight impurities by dialysis. Following dialysis, the solution of the gum is lyophilized. For immunization, a concentrated solution of gum arabic was prepared by dissolving 320 mg of the gum in 2 mL of sterile phosphate buffer (0.02 M phosphate, pH 7) in saline!’ This solution was then mixed with an equal volume of Freund’s complete adjuvant, and samples of 0.4 mL of the suspension were injected intramuscularly in the hind leg of a rabbit weekly in alternate legs for 6 weeks. The animal was then allowed to rest for 2 weeks and the injection schedule was repeated. Four cycles of immunization were used to obtain sera containing a high titer of antibodies. Blood samples were drawn in the second and subsequent cycles and antisera were prepared from the samples by conventional methods. A standard agar-diffusion method was used for detecting precipitin formation in the antibody-antigen reaction. Surprisingly, two sets of antibodies having different migration rates were observed in the serum (Fig. 31). On hydrolysis of the gum with 0.01 N mineral acid one type of antibody no longer gave the precipitin test and on hydrolysis with 1 M acid, neither set of antibodies gave the precipitin test. Reduction of gum with borohydridex4 or oxidation with periodate# also destroyed precipitin-forming ability. The two sets of antibodies have been separated by a two-column affinity chromatography technique shown in Fig. 32. The first column contained an adsorbent of AH-Sepharose 4B coupled to mildly hydrolyzed gum arabic, and the second column contained AH-Sepharose 4B coupled to native gum

ANTI-CARBOHYDRATE ANTIBODIES

A

243

B

FIG.31.-A: Agar-diffusion patterns for anti-gum arabic serum (Se) against gum arabic (G . A), gum hydrolyzate with 0.01 N HCI (.01) gum hydrolyzate with 1 N HCI ( 5 ) and a blank (BI). B: Agar diffusion of gum arabic antibodies against native gum arabic (G * A), reduced (Re) gum arabic, and oxidized (Ox) gum arabic. [Reprinted from Pazur, J. H., Carbohydr. Res. 1991, pp. 1-10. with permission from Elsevier Science Ltd., The Boulevard, Langford Lane, Kidlington OX5 1GB. UK.]

arabic. The columns were attached in series and the immune serum was passed through the first column containing the adsorbent bearing ligands of hydrolyzed gum and then through the second column containing the adsorbent having ligands of native gum. When the non-adsorbed protein had passed through the adsorbents, the columns were separated and the antibodies were eluted separately from each column with 0.2 M phosphate buffer of pH 5.8 containing 0.5 M sodium chloride. The elution patterns are shown in the top portion of Fig. 32. The UV-absorbing substances that

FIG.32.-Two-column affinity chromatography of anti-gum arabic immune serum. The arrangement of columns is shown in the figure. Columns are separated and eluted with 0.5 M NaSCN. Agar-diffusion patterns from immune serum (S), nonadsorbed protein (P), antibodies of Set I (Ah,), and antibodies of Set 2 (Abz) are shown.

244

JOHN H. PAZUR

were eluted were labeled from the first column Ab, and from the second column Ab2. These substances were collected separately and mixed with an equal volume of saturated ammonium sulfate. The precipitates that formed on refrigeration overnight were collected and redissolved in 0.02 M phosphate buffer of pH 7. These solutions were used in additional immunological experiments. The lower portion of Fig. 32 shows insets of agar-diffusion plates in which the immune serum, the non-adsorbed protein, Set 1 antibodies (Ab,), and Set 2 antibodies (Ab2) have been tested against native gum arabic. It may be seen that the original serum (S) contained two groups of antibodies, the nonadsorbed protein fraction (P) did not contain antibodies, and the sets of antibodies (Ab, and Ab2) were separated from each other by the affinity chromatography technique. Density gradient ultracentrifugation revealed that the antibodies in the two sets had the same molecular size of 1.5 X lo5daltons. Electrofocusing of the preparations showed that differences in the mobilities of the members for the sets of isoantibodies did occur (Fig. 33, Nos. 1 and 2). It is apparent from the results that the two sets of isoantibodies are composed of several different isomeric proteins. To test whether all the protein isomers possessed antibody activity, a coupled isoelectrofocusing and agar-diffusion method was used. The results are shown in areas 3, 4, 5, and 6 of Fig. 33. Two different precipitin complexes were formed by the gum and the anti-gum isoantibodies in the precipitin area (5); the top group corresponded to Set 2 antibodies and the lower group to Set 1 antibodies. A precipitin complex formed opposite all of the protein compo-

FIG.33.-lsoelectrofocusing of purified anti-gum arabic antibodies (3) and sets of isoantibodies ( 1 and 2), antibodies embedded in agar (4).agar diffusion area (5). and antigen (6).

ANTI-CARBOHYDRATE ANTIBODIES

245

nents (3) with the gum arabic, and hence all members are anti-gum antibodies. In order to localize the hapten groups of gum arabic that combine with the antibodies of Set 1 and Set 2, a number of carbohydrates were tested as inhibitors of the precipitin reaction by the microdiffusion method, including L-arabinose, D-galactose, L-rhamnose, D-glucuronic acid, and two oligosaccharides, having the structures L-arabinofuranosyl-D-glucuronic acid and D-glucosyluronate-D-galactose,'6isolated by paper chromatography from acid or enzyme hydrolyzates of the gum. The monosaccharides did not inhibit the formation of the precipitin complex. However, the oligosaccharides did inhibit precipitin formation: The first one inhibited Set 2 and the second inhibited Set 1. e. Anti-Xanthan Antibodies.-Xanthan is an exocellular polysaccharide produced by the bacterium Xanthomonas campestris. In structure the polysaccharide is composed of a pentasaccharide repeating-unit shownx5by 8. The polysaccharide is a large polymer having a molecular weight of several million. As a result of its unique structure and high molecular weight, xanthan displays some remarkable rheological properties and functions as a thickening, stabilizing, and emulsifying agent in aqueous solutions. Based on these properties, many uses for xanthan have been developed in the formulation of food items, adhesives, pharmaceuticals, and personal-care products. Xanthan is produced by Xanthomonas campestris growing on D-glucose, by an aerobic submerged fermentation process.x6The production of xanthan involves a multistep fermentation growth process, heat treatment to stop organism growth, and recovery of xanthan from the broth by alcohol precipitation. Finally, the product is dried and used for various purposes. Xanthan has been used to immunize rabbits." Anti-xanthan antibodies have been produced and purification of the antibodies has been achieved by affinity chromatography (Fig. 34). An affinity adsorbent of AH-Sepharose 4B bearing ligands of xanthan was prepared utilizing the carbodiimide reaction.

I 6- Ac - a- D - Man-@- 1)-p - D-GlcA 4

T

1

4.6 - Pyr -p- D-Man 8

246

JOHN H. PAZUR

FIG.34.-Purification of anti-xanthan antibodies (Ab) by adsorption on Xan-Sepharose 4B and elution with NHdSCN. Inset shows agar-diffusion pattern: Pr = serum protein, Xa = xanthan. (Reprinted from Carbohydrafe Polymers, Volume 27. J. H. Pazur. F. J. Miskiel, and N. T. Marchetti, pp. 85-91, copyright 1995, with permission from Elsevier Science Ltd., The Boulevard, Langford Lane, Kidlington. OX5 IGB, UK.)

The UV-absorbing fractions eluted with NH4SCN from the column were combined and mixed with an equal amount of saturated (NH4)2S04.The precipitate that formed on refrigeration overnight was collected and redissolved in a small volume of phosphate buffer. The antibodies were found by the method discussed in Section 2 to be of the IgG class of immunoglobulins, of molecular weight 1.5 X lo5,and to possess a trisaccharide immunodeterminant group of terminal 4,6-pyruvateMan-GlcA-Man (8). Some properties of the antibodies are illustrated in the agar plates reproduced in Fig. 35.

f. Anti-Glucoamylase Antibodies.-Glucoamylase (EC 3.2.1.2), a fungal enzyme, is a novel type of glycoprotein containing 45 carbohydrate side chains, comprising single mannose residues and oligosaccharide chains of mannose, glucose, and galactose.a The chains are 0-glycosylically attached to serine and threonine residues of the protein moiety.” The enzyme hydrolyzes starch completely to glucose and is used industrially in the manufacture of crystalline glucose and high-fructose syrups. A detailed structural analysis by methylation and alkaline &elimination methodsw has shown that the glucoamylase molecule contains 20 single mannose units and 24 oligosaccharide units of various combinations of mannose, glucose, and galactose residues. This diagrammatic representation of a segment of the glucoamylase molecule is shown in Fig. 36 A.

ANTI-CARBOHYDRATE ANTIBODIES

247

FIG.35.-Agar diffusion of xanthan antibodies (Ab) and chemically modified xanthan and inhibitors. A: xanthan (well 1); reduced xanthan (well 2); oxidized xanthan (well 3); deacetylated xanthan (well 4); enzymatically treated xanthan (well 5). B: Xanthan with 6% pyruvate (well 1). xanthan with 4% pyruvate (well 2), xanthan with 2.8% pyruvate (well 3 ) , xanthan with 0.5% pyruvate (well 4). and xanthan with 0.2% pyruvate (well 5). C, D, E: Inhibition of anti-xanthan antibodies by glucuronic acid and mannose; wells 1-6 contain decreasing concentrations of xanthan (1-0.3%) solutions of xanthan; In, antibody + glucuronic acid, Inz antibody + mannose. (Reprinted from Carbohydrate Polymers, Volume 27, J. H. Pazur, F. J. Miskiel, and N. T. Marchetti, pp. 85-91, copyright 1995, with permission from Elsevier Science Ltd., The Boulevard, Langford Lane, Kidlington, OX5 lGB, UK.)

Experiments were undertaken to determine the nature of the immunogenicity of glucoamylase, to identify the immunodeterminant groups and, if possible, to isolate antibodies directed against the enzyme. Antibodies have been obtained" but surprisingly, the immunogenicity of glucoamylase is strongly associated with the carbohydrate portion of the molecule rather than the protein. Further, the immunogenicity is attributable to the oligosaccharide side chains and not to the single mannose units attached to the protein, as established by the results in the upper pattern of Fig. 36 B. Antibodies directed against glucoamylase were isolated by affinity chromatography on glucoamylase-Sepharose 4B from serum of rabbits immunized with gluc~amylase.~' Antibodies were not obtained by elution with mannose, but were obtained by elution with NH4SCN (Fig. 36). Agar diffusion of the antibodies obtained from the glucoamylase-Sepharose 4B column against native glucoamylase and against periodate-oxidized glucoamylase are shown (inset of Fig. 36). The antibody is shown to be IgG in tests with goat anti-rabbit IgA, IgG, and IgM antibodies.

JOHN H. PAZUR

FIG.36.-Anti-glucoamylase antibodies. A: Diagram of segment of the structure of glucoamylase. B: Affinity chromatography of glucoamylase immune serum. Anti-glucoamylase antibodies (Ab), diffused against glucoamylase ( G )and periodate-oxidized glucoamylase (xG). [From J. H. Pazur, K. R. Forry, Y. Tominaga, and E. M. Ball, Biochem. Biophys. Res. Comrnun., 100 (1981) 420-426.1

A gel-electrophoretic pattern of the purified glucoamylase shows a single band by the protein stain, and this band has antibody activity (Fig. 3). The amino acid analysis for selected acids of native and reductive P-eliminated glucoamylase are shown in Table 111. The loss of amino acids due to reduction is balanced, within experimental error, by the gain in newly formed residues listed in Table 111. The loss of carbohydrate residues is one and one half times greater than the loss of amino acids. These results may be interpreted as showing that carbohydrate oligosaccharide chains, as well as monosaccharide chains, exist in the glucoamylase molecule. g. Anti-Tumor Antibodies.-Antigenic glycoproteins may be synthesized in diseased organs and tissues, and some glycoproteins have been

ANTI-CARBOHYDRATE ANTIBODIES

249

TABLE 111 Number of Carbohydrate and Selected Amino Acid Residues per Mole of Glucoamylase before and after Alkaline Reductive &Elimination Reaction

Residues Ser + Thr Gly + Ala + 2-aminobutanoic acid Carbohydrate

Before Reaction

After Reaction

Difference

223 136 84

178 179 6

-45 +43 -78

used as markers of disease.' Carcinoembryonic antigen (CEA) from colon tumors has been perhaps the best-characterized member of this class." However, not all research on this compound has confirmed the high specificity initially reported.'* This glycoprotein contains a high percentage of carbohydrate, rangingy3from 30 to 50%. It seemed likely that the carbohydrate units may function as immunodeterminant groups. The antigen is extracted from colon tumor tissue by the perchloric acid method, and purified by gel filtration and electrophoresis.'* A sample of CEA was provided by Dr. H. Krupey and used in this study. Another method for extracting tumor tissue is with KC1-HCl solution of" p H 2. This method has been used for extracting antigenic polysaccharides from microorganisms."* The protocol for the isolation of tissue samples is presented in Section 111. Samples of colon tumor were used to immunize rabbits. The samples were dissolved in phosphate buffer of pH 7 and mixed with an equal volume of Freund's complete adjuvant. This suspension was used to immunize rabbits subcutaneously. At appropriate times blood samples were drawn and sera were prepared. Figure 37 shows gel electrophoretic and agar diffusion patterns for antibodies and tissue extracts. In the figure it is seen that the TCA sample contained CEA only, but the KCl-HCl sample contained new tumor antigens. It is also seen that both types of sera contained antibodies reactive with the antigens (C of Fig. 37). However, the CEA antibody also reacted with periodate-oxidized antigen, whereas HCl-KCl antibody did not react with periodate-oxidized antigen. In the latter sample, the immunodeterminant group apparently resides in the carbohydrate moiety of the antigen and these units are destroyed by the periodate oxidation. Reaction of the antibodies with oxidized CEA indicates that the immunodeterminant group of this antigen may reside in the protein rn~iety.'~ The presence of two new tumor antigens in human colon with adenocarcinoma is demonstrated by the results of the coupled analysis of electrophoresis and agar diffusion (6, 7, 8, and 9) of Fig. 37. Such antigens are absent in extracts of normal colon tissue (gel 5). The method is readily adaptable to analysis of tumors of other tissues and of other diseased tissue.

JOHN H. PAZUR

250

FIG.37.-Antibodies directed at colon-tumor glycoprotein antigens. A: Carcinoembryonic antigen on gel electrophoresis ( I ) , gel embedded in agar (Z), precipitin area (3). tumor antibody (4). B: Tumor colon KCI HCI extract (6), embedded gel (7), precipitin area (8).antibodies (9). extract of normal colon ( 5 ) . C Agar diffusion of tumor-colon antibodies, C = carcinoembryonic antigen, E = new tumor colon antigens, S, = serum to C EA, S2 = serum to E; x indicates periodate-oxidized antigens. [Data from J. H. Pazur, J. Chromatogr. B., 663 (1995) 51-57.]

3. Specificity for Hexose 1-Phosphates and Others: P-D-GIc-~-P, P-D-GIc NAc-1-P, Shigellu LPS, Others a. Anti-P-D-Glucose-1-P Antibodies.-A novel polysaccharide produced by a group D organism, Streptococcusfueculis strain N, is a tetraheteropolysaccharide of L-rhamnose, D-glucose, D-galactose, and N-acetyl-Dgalactosamine. This organism also produces a diheteropolysaccharide of D-glucose and ~-galactose.”An intriguing aspect of the first polysaccharide is that it contains esterified phosphate. The structure of the polymer was deduced by methylation analysis and alkaline degradationYs and a possible repeating unit is shown by 9. The main chain of the polymer contains

-

3)- L -Rha - ( I - 3 ) - ~ - G a l - ( I - ) 6

T I

L - Rha

3

T

@ 1

1 D

9

Gk

D-

GalNAc - ( I

-

ANTI-CARBOHYDRATE ANTIBODIES

25 1

numerous side chains of /3-D-glucose 1-phosphate. Immunization of rabbits with nonviable cells of S. fuecalis's results in the production of two types of antibodies, one specific for the tetraheteropolymerys and the other specific for the diheteropolymer of glucose and galacto~e.'~ The agar plate showing precipitin-band formation is shown in Fig. 2. The tetraheteropolysaccharide, on acid hydrolysis with 0.01 N HCl, loses its ability to form a precipitin band with the immune serum (Fig. 38A). The diheteropolymer does not lose antigenicity under the same mild hydrolytic conditions. That the 0.01 N acid hydrolysis releases glucose from the tetraheteropolymer is shown by the paper chromatogram (B of Fig. 38). Quantitative hapten inhibition was performed as described earlier7'-74 and the results are shown in Fig. 39. Only 0-Glc-1-P gave a significant inhibition. These results established that /3-D-glucose 1-phosphate is the immunodeterminant group of the tetraheteropolymer.

b. Anti-N-Acetyl-P-D-Glucosamine-1-P Antibodies.-An antigenic heteropolysaccharide has been isolated from the cell wall of group L Streptococci. Preliminary structural information on the compound has been published and shows that the compound is a tetraheteroglycan of L-rhamnose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, and ~ - g a l a c t o s e . ~ ~ ~ ~ ~ The polysaccharide was found to contain esterified phosphate. It is well known that cell-wall carbohydrates are important antigenic components of bacterial cell surfaces. Evidence has been obtained that the antigenic polysaccharide has a novel type of immunodeterminant group. This deter-

FIG. 38.-A: Agar-diffusion pattern of Sfreprococcus faecalis tetraheteropolysaccharide (T) and diheteropolysaccharide (D) hydrolyzates (H,= dihetero and H2 = tetrahetero) in 0.01 N HCI directed against immune serum. B: Paper chromatogram of dilute acid hydrolysis of T.

252

JOHN H. PAZUR

z

9

t 80 -

CONCENTRATION OF INHIBITOR (rnM)

FIG.39.--Inhibition of the precipitin formation of (T) and S. fueculis serum by P-Glc-1-P and other glucose derivatives. (Reprinted with permission from Journal of Biological Chemistry, Volume 257, J. H. Pazur, pp. 589-591, copyright 1982 Journal of Biological Chemistry.)

minant is 2-acetamido-2-deoxy-~-glucose 1-phosphate attached by a diphosphate bond as a side chain to the main chain of the polymer. Blood samples were obtained from a rabbit which has been immunized intravenously by a vaccine of nonviable cells of group L Streptococci. Serum was prepared, and an agar-diffusion plate of polysaccharide and anti-serum is r e p r o d u ~ e d ~ ~ in Fig. 40. It may be noted that the native carbohydrate (N) gives a strong precipitin reaction with immune serum. When the polysaccharide was treated with an inducible enzyme (E) the compound no longer gave a precipitin test. When the compound was subjected to hydrolysis in 0.01 N HCI the product (A) no longer reacted with the serum. The hydrolysis by acid and by enzyme was performed as follows. A sample of the polysaccharide was dissolved in 0.01 N HCI, heated in a boiling-water bath, and analyzed by paper chromatography after 1 h of hydrolysis. Carbohydrate products were detected by the silver nitrate reagent.56Examination of the chromatogram showed that the mild acid hydrolysis liberated N-acetylglucosamine from the group L glycan. The products of enzyme hydrolysis9' were identified in the same way. Additional inhibition results by the microtechnique are shown in Fig. 41. The p anomer of N-acetylglucosamine-1-P functions as inhibitor, but the a does not. c. Monoclonal Antibodies for Shigella frexneri Lipopo1ysaccharide.Monoclonal antibodies having specificity for a lipopolysaccharide from Shi-

ANTI-CARBOHYDRATE ANTIBODIES

253

FIG.40.-Agar-diffusion pattern of the acid hydrolyzate of antigens and anti-group L Sfreprococci serum (S); acid hydrolyzate of group L polysaccharide (well A); native group L polysaccharide (well N), and enzyme hydrolyzate of group L polysaccharide (well E). Photograph of the paper chromatogram, showing release of carbohydrate from the polysaccharide by 1 h of acid hydrolysis, and of enzyme hydrolysis for 6-h periods.

gella flexneri may be produced by immunization of BALBc mice with heatkilled organisms, fusion with the spleen cells with Sp 2/0 plasmacytoma cell line, and subsequent screening for binding activity for the lipopolysaccharide antigen.'9 The monoclonal antibodies for this study were provided by D. R. Bundle. The side chains of the antigenic polysaccharide from Shigellu are composed of N-acetylglucosamine and L-rhamnose.'oo To determine which residue is the determinant group, inhibition by the agardiffusion method was performed,"6 and the results are presented in Fig. 42. The inhibition results show that the N-acetylglucosamine unit (B) is an inhibitor of precipitin formation and the rhamnose unit (C) is not an inhibi-

FIG.41.-Hapten inhibition of group L polysaccharide and antibodies by a- and p-DGlcNAc-I-P. (Reprinted from Journal of Immunological Merhods, Volume 7 5 , J. H. Pazur and S. A. Kelly, pp. 107-116, copyright 1984 with kind permission of Elsevier Science-NL, Sara Burgerhartstraat 25, 1055 KV Amsterdam, The Netherlands.)

254

JOHN H. PAZUR

FIG.42.4nhibition of monoclonal antibodies from Shigellaflexerni by N-acetyl p-D-ghICOSamine (I,), and L-rhamnose ( 12). (Reprinted from Journal of Immunological Methods, Volume 75, J. H. Pazur and S. A. Kelly, pp. 107-116, copyright 1984 with kind permission of Elsevier Science-NL, Sara Burgerhartstraat 25, 1055 KV Amsterdam, The Netherlands.)

tor. Other anti-carbohydrate monoclonal antibodies have been produced but not tested, including antigens from Brucellu, '("Streptococci,In' glycoli~id,'"~ and mouse tumor.@ ' ' d. Other Anti-Carbohydrate Antibodies.-Other anti-carbohydrate antibodies have been prepared but are available only as sera. Yeast mannan containing some a-Glc-1-P units as side chains has been used as an antigen, and these units activate the immune system to produce a-D-glucose-1-P antibodie~."~ Thus, a- and P-D-glucose 1-phosphate antibodies are now available. Antigens having mannose as terminal units have been obtained with synthetic glycoconjugates prepared by coupling mannose oligosaccharides to carrier protein^,'".'"^ and sera containing anti-mannose antibodies have been obtained. Serum having specificity €or N-acetylneuraminic acid has also been prepared.'08 Such serum should be useful for investigating glycoproteins, many of which contain neuraminic acid in their structure. VI. CONCLUSIONS

The isolation, purification, and properties of more than 20 different anticarbohydrate antibodies are described. The isolation and purification are achieved by affinity chromatography of appropriate sera on adsorbents bearing carbohydrate ligands. The properties included agar diffusion, gel electrophoresis, gel and liquid electrofocusing, immunoglobulin type, specificity, hapten inhibition, immunodeterminant groups, sedimentation rate, and molecular weight. The antigens used €or immunization to obtain immune sera include polysaccharides, glycoproteins, and glycoconjugates.

ANTI-CARBOHYDRATE ANTIBODIES

255

The utility of anti-carbohydrate antibodies is varied and depends on the specificity of the antibodies. Antibodies having specificity for polysaccharides of pathogenic organisms are used for the detection and identification of these organisms. This information is required for prescribing treatment of infectious diseases. Antibodies against mammalian antigens from diseased tissue have been produced and often serve as markers of a disease. For example, carcinoembryonic antigen induces antibodies that can be used to detect colon cancer. There are many other examples in which antibodies are used as diagnostic agents, as in detecting the prostate-specific antigen found in the bloodstream of patients with prostate abnormalities. Two types of antibodies generated in response to immunization with polysaccharide gums, one anti-gum arabic and the other anti-xanthan, have been used to detect these gums in commercial products. Shown in Fig. 43 are test results with anti-xanthan antibodies. First, the presence of xanthan was detected in a competitive gum product where patent rights may be involved. Second, the presence or absence of xanthan in such food products as ice cream and salad dressing may readily be determined by the antibody results shown in Plate B of Fig. 43. Of theoretical and practical value has been the use of anti-carbohydrate antibodies to determine the D or L configurations of monosaccharides. Antibodies generated with the D enantiomer of the sugar in the antigen are inhibited by the D enantiomer of the monosaccharide, but not by the L. The reverse holds for antibodies generated with the L enantiomer of the monosaccharide component in the antigen. Some representative

FIG. 43.-Detection of xanthan in food and other products by anti-xanthan antibodies. Plate A: 1 = blank, 2 = xanthan, 3 = commercial product A, 4 = commercial product B, and 5 = xanthan C. Plate B: 1 = xanthan, 2 = salad dressing, 3 = salad dressing with other gum, 4 = ice cream, 5 = ice cream with other gum. (Reprinted from Carbohydrate Polymers, Volume 27, J. H. Pazur, F. J. Miskiel, and N. T. Marchetti, pp. 85-91, copyright 1995, with permission from Elsevier Science Ltd., The Boulevard, Langford Lane, Kidlington, OX5 IGB, UK.)

256

JOHN H. PAZUR

results of this relation are shown in Fig. 44 for glucose, fucose, galactose, and polysa~charides.'~~ All of the anti-carbohydrate antibodies thus far analyzed are composed of sets of isoantibodies. Isoelectric focusing, coupled with agar-diffusion tests, showed that all members of a set form the precipitin complex with the antigen. Isoelectric-focusing patterns are reproduced in Fig. 45 for 18 anti-carbohydrate antibodies which are specific for carbohydrates. Some sets are composed of as few as 5 members and others are composed of as many as 22. For the biosynthesis of a set it is proposed that the immunodeterminant group of the antigen can activate a number of different plasma cells (antibody-producing cells). All of these cells have the same receptors on the cell surface, but the cells differ genetically. A specific activated

FIG.44.-Enantiomeric determination of monosaccharides by use of anti-carbohydrate antibodies. Plate A = Glc, plate B = Fuc, plate C = Gal, plate D = polysaccharide. (Reprinted from Carbohydrate Polymers, Volume 24, J . H. Pazur, A. J. Reed, and N.-Q. Li, pp. 171-175, copyright 1994, with permission from Elsevier Science Ltd., The Boulevard, Langford Lane, Kidlington, OX5 IGB, UK.)

ANTI-CARBOHYDRATE ANTIBODIES

257

FIG.45.-Electrofocusing of anti-carbohydrate isoantibodies.

plasma cell synthesizes only one type of one light chain and one type of heavy chain, and the result of the finished process is a group of homogenous antibodies. Other cells which differ genetically synthesize different light and heavy chains and produce different sets of antibodies that are specific for the common antigen. Depending on the number and types of plasma cells activated by the immunodeterminant group of a single antigen, the number of members in a set will be determined. Different animals possess the capability to respond differently to an antigen and may elaborate different sets. Thus, three rabbits subjected to immunization with the same type

258

JOHN H. PAZUR

of antigen produced sets of anti-lactose antibodies numbering 13, 16, and 21 isoantibodies in the respective sets. ACKNOWLEDGMENTS 1 express sincere appreciation to my editorial assistants, Eileen McConnell and Jean Pazur, for invaluable help in the preparation of the manuscript; t o former collaborators, Judy Kane and Walter Karakawa, for sharing significant experimental data; and to Margery Worrick for technical assistance with the figures.

REFERENCES (1) H. N. Eisen, Immunology, 2nd edn., Harper & Row, Hagerstown, MD, 1980. (2) C. Bertozzi and M. Bednarski, Carbohydr. Rex, 223 (1992) 243-253. (3) J. H. Pazur, K. L. Dreher, and L. S. Forsberg, J. Biol. Chem., 253 (1978) 1832-1837. (4) IUPAC-IUB Commission on Biochemical Nomenclature, J. Biol. Chem., 252 (1977) 5939-5941. (5) J. H. Pazur, Adv. Carbohydr. Chem. Biochem., 39 (1981) 405-447. (6) J. H. Pazur, M. E. Tay, B.A. Pazur, and F. J. Miskiel,J. Protein Chem., 6 (1987) 387-399. (7) G. Kohler and C. Milstein, Eur. J. ZmmunoL, 6 (1976) 511-519. (8) D. E. Yelton and M. D. Scharff, Ann. Rev. Biochem., 50 (1981) 657-680. (9) P. Gold and S. 0. Freedman, J. Expt. Med., 121 (1965) 439-461. (10) J. H. Pazur, F. J. Miskiel, and N. T. Marchetti, Carbohydr. Polym., 27 (1995) 85-91. (11) E. Heftmann, Chromatography, 5th edn., Part A, Elsevier, Amsterdam, 1992. (12) P. Cuatrecasas, M. Wilchek, and C. B. Anfinsen, Proc. Natl. Acad. Sci. USA, 61 (1968) 636-643. (13) R. Axen, J. Porath, and S. Ernback, Nature, 214 (1967) 1302-1304. (14) H. G. Khorana, Chem. lnd. (London) (1955) 1087-1088. (15) J. H. Pazur, J. S. Anderson, and W. W . Karakawa,J. Biol. Chem., 246 (1971) 1793-1798. (16) F. J. Miskiel and J. H. Pazur, Carbohydr. Polym., 16 (1991) 17-35. (17) J. H. Pazur and T. Ando, J. Biol. Chem., 234 (1959) 1966-1970. (18) J. Krupey, P. Gold, and S. 0. Freedman, J. Expt. Med., 128 (1968) 387-398. (19) J. H. Pazur, J. Chromatogr. B., 663 (1995) 51-57. (20) J. H. Pazur, Carbohydr. Res., 107 (1982) 243-254. (21) R. Kornfeld, J. Keller, J. Baeziger, and S. Kornfeld, J. Biol. Chem., 246 (1971) 32593268. (22) P. Cuatrecasas. J. Biol. Chem., 245 (1970) 3059-3065. (23) Pharmacia, Affinity Chromatography, Principles & Methods, Laboratory Separation Division, S-751 82 Uppsala, Sweden, 1986-1988. (24) G. R. Gray, Arch. Biochem. Biophys., 163 (1974) 426-428. (25) A. M. Jeffrey, D. A. Zopf, and V. Ginsburg, Biochem. Biophys. Rex Commun., 62 (1975) 608-613. (26) J. H. Pazur, M. S. Erikson, M. Tay, and P. Z. Allen, Carbohydr. Rex, 124( 1 983) 253-263. (27) 0. Ouchterlony, Acta Puthol. Microbiol., 26 (1949) 507-510. C.A. 43 (1949) 9227. (28) P. Doerr and A. Chrambach, Anal. Biochem., 42 (1971) 96-107. (29) B. J. Davis, Ann. N.Y.Acad. Sci., 121 (1964) 404-427. (30) J. H. Pazur, B. Liu, and F. J. Miskiel, Biotech. Appl. Biochem., 12 (1990) 63-78. (31) M. Brakke, Anal. Chem., 5 (1963) 271-283.

ANTI-CARBOHYDRATE ANTIBODIES

259

J . H. Pazur, K. Kleppe, and J. S. Anderson, Biochim. Biophys. Acta, 65 (1962) 369-372. J . H. Pazur, B. Liu, and T. F. Witham, J. Protein Chem., 13 (1994) 59-66. J. H. Pazur and K. Kleppe, Biochemistry, 3 (1964) 578-583. R. G. Martin and B. N. Ames, J. Biol. Chem., 236 (1961) 1372-1379. J. H. Pazur and S. A. Kelly, J. Immunol. Meth., 75 (1984) 107-116. J. H. Pazur, F. J. Miskiel, N. T. Marchetti, and H. R. Shiels, Pharm. Pharmacol. Lett., 2 (1993) 232-235. (38) D. French, D. W. Knapp, and J. H. Pazur, J. Am. Chem. Soc., 72 (1950) 5150-5152. (39) Z. Dische, in D. Click (Ed.), Methods Biochemical Analysis, Vol. 11, Interscience Publishers, New York, 1955, pp. 313-358. (40) M. R. J. Salton, The Bacrerial Cell Wall, Elsevier Publishing Co., Amsterdam, (1964) pp. 22-57. (41) J. T. Park and R. Hancock, J. Gen. Microbiol., 22 (1960) 249. (42) R. C. Lancefield, J. Exptl. Med., 57 (1933) 571-595. (43) A. T. Fuller, Brit. J. Exptl. Path., 19 (1938) 130-139. (44) A. Jeanes, J. E. Pittsley and F. R. Senti, J. Applied Polymerase Sci., 5 (1961) 519-526. (45) A. Neville, J. Agr. Sci., 5 (1913) 113-128. (46) M. Glicksman, Food Hydrocolloids, Vol. 2, CRC Press, Inc., Boca Raton, FL, 1983, pp. 8-29. (46a) J. Defaye and E. Wong, Carbohydr. Res., 150 (1986) 221-231. (47) J. H. Pazur, H. Knull, and A. Cepure, Carbohydr. Res., 20 (1971) 83-86. (48) J. H. Pazur, A. Cepure, J. A. Kane, and C. G. Hellerqvist, J. Biol. Chem., 248 (1973) 279-284. (49) J. H. Pazur, F. J. Miskiel, T. W. Witham, and N. Marchetti, Carbohydr. Res., 214 (1991) 1-10. (SO) 0. T. Avery and W. F. Goebel, J. Expt. Med., 50 (1929) 533-550. (51) 0. T. Avery, W. F. Goebel, and F. H. Babers, J. Expt. Med., 55 (1932) 769-780. (52) P. Z. Allen, 1. J. Goldstein, and R. N. Iyer, Biochemistry, 6 (1967) 3029-3036. (53) R. S. Martineau, P. Z. Allen, I. J. Goldstein, and R. N. Iyer, Immunochemistry, 8 (1971) 705-718. (54) T. V. Tittle, A. Mawle, and M. Cohn, J. Immunology, 135 (1985) 2582-2588. (55) R. U. Lemieux, D. A. Baker, and D. R. Bundle, Can. J. Biochern., 55 (1977) 507-512. (56) F. C. Mayer and J. Lamer, J. Am. Chem. SOC.,81 (1959) 188-193. (57) J. H. Pazur, H. R. Knull, and C. E. Chevalier, J . Carbohydr. Nucleos. Nucleor., 4 (1997) 129-146. (58) S. M. Partridge, Biochem. J., 42 (1945) 238-248. (59) L. Warren, Nature, 186 (1960) 237-238. (60) J. H. Pazur, B. Liu, and Nan-Qian Li, Natural Product Len, 1 (1992) 51-57. (61) Y.C. Lee, C. P. Stowell, and M. J. Krantz, Biochemistry, 15 (1976) 3956-3963. (62) J. H. Pazur, B. Liu, Nan Q. Li, and Y. C. Lee, J. Protein Chem., 9 (1990) 143-150. (63) J. H. Pazur, B. Liu, and T. F. Witham, J. Protein Chem., 13 (1994) 59-66. (64) J. H. Pazur, K. L. Dreher, R. L. Kubrick, and M. S. Erikson, Anal. Biochem., 126 (1982) 285-294. (65) J. H. Pazur, A. J. Reed and R. E. Scrano, Glycobiology, 6 (1996) 763. (66) K. Hunt and J. K. N. Jones, Can. J. Chem., 40 (1962) 1266-1279. (67) L. Gahnberg and B. Krasse, Infect. Immun., 33 (1981) 697-703. (68) R. C. Lancefield, Harvey Lectures, 36 (1940-41) 251-290. (69) R. M. Krause and M. McCarty, J. Exptl. Med., 115 (1962) 131-140. (70) R. M. Krause, Bacreriol. Rev., 27 (1963) 369-380. (32) (33) (34) (35) (36) (37)

260

JOHN H. PAZUR

(71) J. E. Coligan, W. C. Schnute, and T. J. Kindt, J. Immunol., 114 (1975) 16541658. (72) J. H. Pazur and L. S. Forsberg, Methods Carbohydr. Chem., 8 (1980) 107-116. (73) M. McCarty and R. C. Lancefield, J. Exp. Med., 102 (1955) 11-28. (74) 0. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall, J . Biol. Chem., 193 (1951) 265-275. (75) G. M. Edelman. D. E. O h , J. A. Gally, and N. D. Zinder, Proc. Narl. Acad. Sci. USA, 50 (1963) 753-761. (76) E. Valmet, Science Tools, 15 (1968) 8-11. (77) B. A. Askonas, A. R. Williamson, and B. E. G. Wright, Proc. Narl. Acad. Sci., 67 (1970) 1398-1403. (78) M. Potter and C. R. Boyce, Nature (London), 193 (1962) 1086-1087. (79) J. H. Pazur, M. E. Tay, S. E. Rovnak, and B. A. Pazur, Immunology Leu., 5 (1982) 285-291. (80) M. Potter, Federation Proc., 29 (1970) 85-91. (81) J. H. Pazur and T. Ando, Arch. Biochem. Biophys., 93 (1961) 43-49. (82) J. H. Pazur, Y. Tominaga, K. Dreher, L. S. Forsberg, and B. M. RomanicJ. Carbohydr. Nucleos. Nucleotid., 5 (1978) 1-14. (83) J. H. Pazur, Y. Tominaga, C. W. DeBrosse, and L. M. Jackman, Carbohydr. Rex, 61 (1978) 279-290. (84) H. E. Conrad, J. B. Bamburg, J. D. Epley and T. J. Kindt, Biochemistry, 5 (1966) 28082817. (85) P. E. Jansson, L. Kenne and B. Lindberg, Carbohydr. Res., 45 (1975) 275-282. (86) D. J. Pettitt, in G. 0. Phillips, D. J. Wedlock, and P. A. Williams (Eds.), Gums and Stabilizers for the Food Industry, 2, Pergamon Press, New York, 1986, pp. 451-463. (87) J. H. Pazur, F. J. Miskiel, and N. T. Marchetti, Carbohydr. Polym., 27 (1995) 85-91. (88) J. H. Pazur, Y. Tominaga, L. S. Forsberg, and D. L. Simpson, Carbohydr. Res., 84 (1980) 103-114. (89) J. H. Pazur, Y.Tominaga, and S. A. Kelly, J. Protein Chem., 3 (1984) 49-62. (90) J. H. P a m , B. Liu, and F. J. Miskiel, Biotech. Appl. Biochem., 12 (1990) 63-78. (91) J. H. Pazur,K. R. Forry,Y.Tominaga, andE. M. Ball, Biochem. Biophys. Res. Commun., 100 (1981) 420-426. (92) W. Zimmerman and J. Thompson, Tumor Biol., 11 (1990) 1-4. (93) J. L. Urban and H. Schreiber, Annu. Rev. Immunol. 10 (1992) 617-644. (94) S. Hammarstrom, E. Engvall, B. G. Johansson, S. Svensson, G. Sundblad, and I. J. Goldstein, Proc. Natl. Acad. Sci. USA, 72 (1975) 1528-1532. (95) J. H. Pazur, J. Biol. Chem., 257 (1982) 589-591. (96) J. H. Pazur, A. Cepure, J. A. Kane, and W. W. Karakawa, Biochem. Biophys. Res. Commun., 43 (1971) 1421-1428. (97) W. W. Karakawa, J. E. Wagner, and J. H. Pazur, J. Immunol., 107 (1981) 554-562. (98) J. H. Pazur, Anal. Biochem., 145 (1985) 385-392. (99) N. I. A. Carlin, M. A. J. Gidney, A. A. Lindberg, and D. R. Bundle, J. Immunol., 137 (1986) 2361-2366. (100) L. Kemne, B. Lindberg, K. Peterson, and E. Romanowska, Carbohydr. Res., 56 (1977) 363-370. (101) D. R. Bundle, J. W. Cherwonogrodzky, M. A. J. Gidney, P. J. Meikle, M. B. Perry, and T. Peters, Infect. Immun., 57 (1989) 2829-2836. (102) M. Cunningham, N. C. Hall, K. K. Krishner, and A. M. Spanier, J . Immunol., 136 (1986) 293-298.

ANTI-CARBOHYDRATE ANTIBODIES

261

(103) W. W. Young, Jr., J. Portowkalian,and S. Hakomori, J. Eiol. Chem., 256 (1981) 1096710972. (104) D. V. Gold and M. J. Mattes, Tumor Eiol.,9 (1988) 137-144. (105) P. N. Lipke, W. C. Raschke. and C. E. Ballou, Curbohydr. Res., 37 (1974) 23-35. (106) D. A. Zopf, C.-M. Tsai, and V. Ginsburg, Arch. Eiochem. Eiophys., 185 (1979) 61-71. (107) F. Vargas, S. H. Khan, and K. R. Diakun, Immunol. Invest., 21 (1992) 671-684. (108) D. F. Smith and V. Ginsburg, J. Eiol. Chem., 255 (1980) 55-59. (109) J. H. Pazur, A. J . Reed. and N.-Q. Li, Curhohydr. Polym., 24 (1994) 171-175.

This Page Intentionally Left Blank

ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY. VOL. 53

COMPLEXES OF STARCH WITH INORGANIC GUESTS BY PIOTRTOMASIK AND CHRISTOPHER H. SCHILLING Department of Chemistry and Physics. The Hugon Kollataj Academy of Agriculture. 30 059 Cracow. Poland; and Ames Laboratory* and Department of Materials Science and Engineering. Iowa State University. Ames. Iowa 5001I

I . Introduction ....................................................... I1. The Starch-Iodine Complex ........................................... 1. Historical Background 2 . Preparation of the Iodine Complex 3. Effects of the Origin and State of the Starch 4. Solvent Effects 5. Electrolyte Effects ............................................... 6. Effects of Proteins and Other Organic Compounds 7. Structure of the Complex 8. The Mechanism of Complex Formation 9. Properties of the Iodine Complex ................................... 10. Applications of the Complexation and the Complex ..................... 111. Starch-Water Complexes 1. Introduction 2. The Status of Water in Starch ...................................... 3. The Mechanism of Water Sorption ....................................... 4 . Significance of the Origin of Starch 5. Analysis of the Water Content IV . Starch Complexes with Other Nonmetallic Guests 1. Introduction .................................................... 2. Complexes with Arrhenius Acids and Bases 3. Complexes with Salts References ........................................................

............................................ .................................. ........................... .................................................. ...................... .......................................... ...............................

............................................. ....................................................

.................................. ...................................... .......................... ........................... .............................................

263 264 264 266 268 270 272 272 274 278 284 296 298 298 300 304 307 310 312 312 313 316 328

I . INTRODUCTION The macrostructure and microstructure of starch lead to the ready formation of inclusion complexes and surface adsorbates.' Inclusion complexes form by involvement of the inner core of the amylose helix. the intergranular * Ames Laboratory is operated by Iowa State University under the contract number W-7405eng-82 with the U.S. Department of Energy .

0065-2318/98$25.00

263

Copyright 0 19Y6 by Academic Ress. All rights of reproduction in any form reserved.

264

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

space (capillaries), or the starch matrix. All three of these types of guestmolecule binding to starch are accompanied by surface sorption? making the meaning of "inclusion complexes" rather unclear because in all cases, the contact between the guest molecule and starch can take place simultaneously. The study of water in starch illustrates the entire complexity of the matter (see ref. 3 and references therein). Another problem arises from misinterpretation of experimental data; the starch-iodine complex (see later discussion) is a prime example. Starch-guest molecule compounds in inclusion complexes are usually nonstoichiometric species. On the other hand, in the case of amylose such compounds are stoichiometric, but their composition is not repeatable. Starch complexes may consist of partly physical mixtures, adsorbates, and true inclusion complexes formed by direct involvement of dipolar interactions, host-guest hydrogen bonds, andlor clathration-like interactions within the starch matrix. Inclusion complexes of amylose are rather well defined, and a consistent theory of such complexes is available that explains amylose complexes with iodine, fatty acids, alcohols, and other guest rnole~ules.~*~ This subject is surveyed in this article because of the growing interest and importance of such complexes in pharmacology and in the food industry. It is probable that starch in its biological sources (tubers, granules) exists in the form of native complexes with proteins, lipids, mineral salts, and water. 11. THESTARCH-IODINE COMPLEX This topic has already been reviewed in several s0urces,6-~~ most recently in 1984.

1. Historical Background The first papers published on the blue color formed by the interaction of starch with iodine appeared in 1814 (ref. 16) and 1815 (ref. 17). Several papers were published up to 1944, when Rundle et ~ 1 . established '~ the correct qualitative structure of the starch-iodine complex. Since then, interpretations of the structure of this so-called starch blue have been revised several times. Earlier papers variously reported that it is a physical mixture," a solid?' and a ~olloidal~"~'*-~~ solution of iodine, with starch acting as protective colloid. Later the substance was characterized as surfaceabsorbed i ~ d i n e . ~ There ' - ~ ~ is even a papesowhich rejects all starch-iodine interactions except catalytic interactions. Iodine in the presence of oxygen supposedly changes the structure of starch. According to that authos" there is no iodine in the starch blue. A s u g g e ~ t i o nwas ~ ~ .also ~ ~ made that

COMPLEXES OF STARCH WITH INORGANIC GUESTS

265

starch-iodine interactions are not purely physical (absorption), but also chemical. Since the UV spectra of the complexes are identical to those of starch itself, the suggestion of chemical iodine-starch bonding was rejected.” Andrews and G o e t ~ c hwere ~ ~ first to assign a formula for the complex. Adsorption of iodine by starch was quantitatively analyzed by Harrisonz3 . ~ ~ studies entailed the use of I2 as well as by Angulescu and M i r e ~ c uBoth in solutions of potassium iodide. Adsorption took place according to the Freundlich isotherm: C, = K CP

(1)

where C, is the concentration of iodine taken up by starch and C is the concentration of iodine remaining in solution after adsorption. K and p are constants that are independent of the concentration of potassium iodide. The latter is not adsorbed by starch. At this time the role of potassium iodide in the formation of starch blue was unclear. Some paper^^^,^^ considered it an unnecessary component. However, B ~ r g s t a l l e rdemonstrated ~~ that increasing the amount of potassium iodide as well as the acidification of the reaction mixture turns the blue color into red-violet and brown. The color changes were reversible on dilution. Discoloration of the blue complex can be effected by the addition of an excess of starch36 as well as by acoustic vibrations above3’ 250 Hz. Several other paper^^*-^^ have pointed to potassium iodide as an essential component of the blue complex. The misunderstanding of the role of potassium iodide could be due to the fact that the reaction was run in aqueous solutions. Elemental iodine obviously disproportionates under conditions of the formation of the complex, producing some I- ions necessary for the formation of 13- ions, which are in turn responsible for the formation of the blue complex. The 13- ions are readily adsorbed by starch, whereas I2 is adsorbed only to a small extent, and KI is not adsorbed at all.z9The negative results of the preparation of starch blue from starch and iodine in CC14 or benzene also speak in favor of such an explanation. A blue color is also formed if the 103- is present rather than the 13- ion.44The microscopic and macroscopic properties of the complexes prepared with iodine in water and with the 12-KI solution are also different.45 Bear4‘ as well as Katzbeck and Kerr47 established a solution to this problem. The authors observed that it is the so-called V-type (pregelatinized) starch that adsorbs iodine, whereas starch with the A- and Bcrystallographic patterns is incapable of adsorbing iodine. The experiments of Rundle er appeared to be crucial in this respect and have shown that starch pretreated with 1-butanol adsorbs iodine vapor rapidly, even if the starch is thoroughly dried. In addition, if there is some inclusion of 1~

1

.

~

~

9

~

’

266

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

butanol in starch, the iodine replaces it. Knowledge of the conformation of the V-type amylose finally led to the conclusion that iodine occupies the interior of the amylose helix. As with 1-butanol (and also other alcohols), aqueous KI as well as KI itself are responsible for generation of the Vtype starch. Iodine in absolute ethanol and dry starch do not form any blue c0mplex.4~-~~ Detailed studies5’ illustrated that the A-type starch also assumes a helical structure like that of the V-type starch. However, in contrast to the helical structure of V-starch, the A-starch forms a double left-hand helix with 4 water molecules per 12 glucose units (see Fig. 1). It is possible that such packing makes the structure inpenetrable by the iodine species.52

2. Preparation of the Iodine Complex According to Rundle and French?’ a complex of amylose with iodine can be produced by staining amylose (precipitated with butanol) with iodine vapor, where the amylose was dried over P2OSprior to staining. Ha1lgred3 proposed a mechanical method in which an oven-dried (100-110°C) starch was suspended in an ethereal solution of iodine. The 1005 weight ratio is maintained. Diethyl ether is then allowed to evaporate off. Complexes that are partially saturated with ether are brick-red in color and turn grayyellow upon complete drying. These complexes turn blue after subsequent moistening. Within 14 months of storage in a tightly stoppered bottle, the dry complex loses only 0.6% of its iodine, whereas the blue moistened complex loses almost half its iodine. No crystals of iodine are observed in such a preparation. A British patents4 recommended blending starch suspended in a polyhydric alcohol such as ethylene glycol or glycerol with either an ethanolic or an ethereal solution of NaI and iodine. After this mixture is kept for 8 days at room temperature, the solvent and uncombined iodine are removed by washing. @-Typeamylose formed a complex with iodine vapor at 80-90°C leaving a compound of the composition of (C36H6003013)2 in the form of a dry powder.” The preparation of starch blue in aqueous solution with iodine-iodide mixtures is the most common procedures. According to the method of Palss6 starch (10 mg) of water (5 mL) is boiled for 5 min and blended with 7.6 X lo-’ m o m (5 mL) of an aqueous solution of iodine and 4.27 X lo-’ mol/L (5 mL) of an aqueous solution of KI. The complex is precipitated by the addition of an aqueous solution of KF (10 mol/L). The precipitate is centrifuged (5000 rpm for 10 min) and washed with aqueous KF (1 mol/L). The Vanino reagent (barium permanganate) also precipitates iodized ~tarch.~’ The resulting complex is stable and has a defined stoichiometry. A similar procedure was described by Meyer and Bernfeld.58Chinoy

COMPLEXES OF STARCH WITH INORGANIC GUESTS

267

a

FIG. 1.-Representation of double-helix packing and unit cells in A and B crystalline starches (a and b, respectively). Dashed lines represent hydrogen bonds. Water molecules have been omitted. (Reprinted with permission from A. Imberty, A. Buleon, Vinh Tran, and S. Perez, Staerke, 43 (1991) 375-384.)

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

268

et ~ 1 . ~boiled ’ starch (0.5 g) in distilled water (100 mL); after cooling the solution (10 mL) was treated with 10 M iodine solution. Ethanol (20 mL) was added after 1 min, and the starch-iodine complex precipitated within 5 min. The filtered precipitate was washed with ethanol (200 mL) and then oven-dried for 12 h. Boutriac and Fabrym studied the effect of the ratio of reagents as well as the amount of ethanol. The results are reported in terms of the RFvalue of the blue complex in paper chromatography. The simplest method of preparation involves either rapid or slow titration of amylose (0.05 g/L) with an aqueous solution of I2 (4-24 mg/L) and KI (2 g/L).6’ Kudla and Tomasik62attempted the preparation of a starch-iodine complex by compression of starch with iodine up to 1.2 X 10’ Pa; the results of thermal analysis indicated that a complex was formed.

3. Effects of the Origin and State of the Starch Both the amylose and amylopectin components of starch form complexes with iodine, but early studies showed that there is no connection between the iodine reaction and the reducibility of starch fractions.63The complex of amylose is pure blue, whereas the complex of amylopectin is blue~ i o l e t . Thus, ~ ~ - ~the varying amylose-to-amylopectin ratio can be one of the factors responsible for the various shades of blue color exhibited by various varieties of starch. Amylopectin takes up less iodine than does amylose. Also the course of complex formation uptake is different, as is evidenP from Fig. 2. The state of the starch influences the uptake of iodine. Native, raw starch adsorbs less iodine, whereas cooked starch, and cooked and shaken starch, adsorb progressively larger amounts, a phenomenon attributed to the state of starch d i ~ p e r s i o n . ~Huebner ~ . ~ ~ - ~and ~ Venkataraman6’ demonstrated the same phenomenon. Their results showed that gelatinized starch adsorbs 0.26 0.24

-

>

E

0.18

0

5D

10.0

15.0

20.0 mL

ImM iodine solution FIG.2.-Potentiometric titration with 0.05%N aqueous Kls solution of butanol-precipitated corn amylose (100 mL of 0.01% solution) (upper line) and corn amylopectin (100 mL of 0.04% solution) (lower line). [Reprinted with permission from Bates er Copyright (1943) American Chemical Society.]

COMPLEXES OF STARCH WITH INORGANIC GUESTS

269

TABLE I Adsorption of Iodine from Aqueous II-KI Solutions by Starch of Various Origins69

Mass of Adsorbed Iodine per 100 g of Starch Starch Variety

Original

Gelatinized

Maize Potato Rice Sago Tapioca Wheat

18.61 18.18 19.01 17.32 18.73 18.52

20.18 19.74 20.28 18.97 20.40 20.12

more iodine than native starch, regardless of its origin (see Table I). The same authors observed that the smallest granules of starch exhibit the highest iodine uptake. The differences in iodine uptake vary from 4.5 up to 25.3 wt % of adsorbed i ~ d i n e . Amylose ~ ~ . ~ ~ from rice binds 18.9% of iodine, regardless of the molecular weight of the particular sample^.^' Table I1 and results by other a u t h o r P 6 show that the size of the granules is not the only factor controlling the dependence of the iodine uptake on the origin of starch. Figure 3 shows that differences in iodine uptake may be ascribed solely to the varying amylose and amylopectin content in particular starches.73The amount of iodine adsorbed by amylose is a function of the length of its helical chain; the amount of iodine adsorbed by amylopectin

TABLEI1 Adsorption of Iodine from Benzene Solutions by Different Varieties of Starch' Variety

Adsorbed Iodine, wlw%

Maize Potato Rice Sago Tapioca Wheat

4.85 2.97 15.99 1.28 1.29 3.08

a Reproduced by permission from Huebner and Venkataraman!'

270

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

0.18 I

0

I

1

10.0

5.0

15.0

L

20.0 mL

1mM iodine solution

FIG.3.-Potentiometric titration with 0.001 N aqueo s K13 solution of 100 mL of 0.04% solution of the following starch varieties: x = wheat; = rice; 0 = corn; 0 = potato; A = tapioca. (From Bates et

4

depends on the degree of b r a n ~ h i n g . ~ ~ . "Table * ~ ~ -I11 ~ ~shows the iodinebinding power for amylopectin of various origins. The presence and content of phosphoric acid moieties in starch also does not affect the course of r e a c t i ~ n . For ~ ~ .several ~~ types of amylose, the iodine affinity varies between 18.5 and 20% in a 0.05 M solution of iodine.79 4. Solvent Effects

As already discussed on p. 265, iodine uptake by starch is facilitated by water (together with 13-ions), 1-butanol, or other alcohols. This is attributed to the conversion of A- and B-type starch into V-type starch. Huebner and Venkataramad9 demonstrated that starch can adsorb iodine from nonaqueous and not necessarily polar solvents, as shown in Table IV. Iodine adsorption by starch in aqueous ethanol increases as the ethanol content increases. Again, the solvent effect depends on the origin of the starch (Table 11). The varying effects observed using benzene, ethanol, and chloroform may also be ascribed to the use of starches of different origin TABLE 111 The Binding of Iodine by Different Varieties of Amylope~tin'~ Amylopectin Variety

Amount of Absorbed Iodine, O/O

Barley Hevea brasiliensis Oat Waxy maize Wrinkled pea

2.6 0.8 3.2 1.4 3.4

COMPLEXES OF STARCH WITH INORGANIC GUESTS

27 1

TABLE IV Absorption of Iodine by Starch from Various Organic Solvents@ Solvent

Amount Absorbed, %

Aqueous alcohol 99% 80% 60% 55% 50% 45% 40% 20%

4.05 8.39 12.44 13.42 15.13 17.07 21.18 53.42 61.87 6.71 12.34

0%

Benzene Chloroform

in every case. For instance, the enormously strong effect of benzene on starch was interpreted as the result of azeotropic evacuation of water from starch capillaries and he lice^.^ Such action could certainly change the original structure of the granules and the helix itself. However, frequently interpretations seem to be oversimplified. Ono et observed that the starchiodine reaction failed in dimethyl sulfoxide containing less than 28 moles of water per dm3. The amylose complex with iodine is slightly less sensitive to the addition of dimethyl sulfoxide than is the complex of amylopectin.81 W. T. and G. T. Smithx2estimated the minimum water contents with various solvents that would allow the formation of starch blue (Table V). The authors interpreted their results in terms of the stabilization of the amylose helix. Such stabilization is suggested to be a function of the polarity of the solvents investigated. As shown by Mazurkiewicz and Tomasik,83 different TABLE V Minimum Water Concentrations in Organic Solvents Providing Color as a Result of Starch-Iodine Reactions** Solvent

Minimum Water Concentrations, v/v%

N-Methylacetamide Methanol Ethanol Dimethyl sulfoxide N,N-Dimethylformamide 1.4-Dioxane Acetonc

39 47 52 53 58 58 68

212

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

organic solvents undergo hydration by various numbers of water molecules. In the case of high solvent-to-water ratios, bulky, stable solvates are formed which are characterized by, among other things, increased viscosity. Thus, under certain conditions of stoichiometry, water molecules are no longer available to the starch, and the solvent acts as a nonaqueous one with respect to starch. The conditions of solvation of the I2 molecule and the Ij- ion as well as the effect of the solvents on the I2 + I13- equilibrium may also be of significance (see, for instances, Tomasik et dM).

*

5. Electrolyte Effects The blue reaction is stronger with the addition of HI or KI.x5Electrolytes intensify the blue color by the coalescence of smaller particles into larger ionsx6;the size of the cation is an important However, at concentrations as low as 1 ppm, Fe(II1) (and also N203)” and H I 0 2 5 obstruct this reaction. Improved stability of the blue color is reported using NH41 and I2 instead of the KI-I2 mixture.g0More-detailed studies by Kuge and Ono91*y2 as well as by Miyazaki9jhave pointed to the importance of cations and anions in the observed effect. Thus, chlorides and bromides interact strongly with iodine ions to form iodine-bromide and iodine-chloride anions. This interaction affects the length of the chromophore of the complex that is responsible for the blue color. Figure 4 shows the effects of various salts on the formation of the amylose-iodine complex, as measured by the frequency of the longest-wavelength absorption band of the visible spectrum, and by the absorbance of that band. It may also be seen that the effect of both cations and anions depends on their concentration (Fig. 5). Cations of higher charge cause their effect at lower concentrations. The conclusions of the authors focus on the ionic strength of solutions in which the blue complex is intended to be formed. This problem points to the importance of the concentration of 13- ions themselves in achieving such a complex. Indeed, such an effect has been observed and is discussed later in connection with the mechanism of formation of the complex. On the other hand, nitrile anions inhibit the blue reaction. This inhibition can, however, be reversed by the addition of rhodanide anions.y4 Many electrolytes precipitate starch iodide from s o l ~ t i o n . ~ ~ ~ ~ ~ * ~ ~ 6. Effects of Proteins and Other Organic Compounds It was realized long ago that a number of organic compounds can obscure the blue reaction.y7 This effect is caused by the formation of inclusion complexes by such compounds. Hence, the iodine reaction is widely used as the test for complexation of starch, mainly amylose, with many organic

COMPLEXES OF STARCH WITH INORGANIC GUESTS

273

0.5

E

03 0.2.

0.1

'

[MI FIG.4.-Effects of various salts on the formation of the amylose-iodine complex. The effect is expressed as the shift of the 605-nm band (above) and the variation of the extinction of that band (below). 1, KCI; 2, NaN03; 3, (NH&SO,; 4, CaCI2; 5, ZnSO,; 6, KBr; 7, KI. (From Kuge and Ono.")

guest molecules, in both a qualitative and a quantitative sense. Since it is known that adrenaline98 and many other compounds99prevent the formation of the blue complex, and that proteins (such as those in blood, plasma, serum, or bacterial vaccines) also affect this reaction, the blue reaction has

0.4 ~

0.3

FIG.5.-Changes of absorbance of the amylose-iodine complex (at 610 nm with increasing concentrations of various salts): 1, A12(S04)3;2, Pb(NO&;3, Na,SO,; 4, NH4Cl;5 , CH3C02Na; 6, Sr(NO&: 7. KI; 8, KNO3. (From Kuge and Ono.")

274

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

significant value in toxicology studies and clinical analysis, and it can be a method of colorimetric estimation of proteins in immunity 7. Structure of the Complex

Although the stoichiometry of complexes can be defined, different compositions have been reported. The composition {[(C6HlnOS)4I]4KI},is given when the complex is prepared by blending approximately 0.5% of an aqueous suspension of starch with an excess of iodine in 0.1 N KI.lo2 Murrayln3 proposed the ionic structure of complexes obtained by shaking a starch solution containing KI with a solution of iodine in C C 4 . The author presented several possible formulae (C6Hl0O5),KISwith n = 15. A t high concentrations of KI, compositions of (ChHI0O5),,KI3and even (C6H100~)nK12 have been reported. Euler and MyrbacklW reported the formation of two defined compounds which are stable at a given dissociation pressure of iodine. The existence of these two compounds was later confirmed" by UV spectrophotometric studies. However, according to Meyer and Bernfeld,5x amylose forms several complexes, the composition of which ranges from (C6Hlo05)10-,,12,to (C6H1005)20n12n. A composition (C6H100s)8n12,1 was also reported.'"' In view of information presented in the next paragraph, it is not reasonable to anticipate a universally valid formula of the blue complex. Only general rules regarding the formation of the complex and general structural data are available. The amylose and amylopectin portions of the complex have obviously different structures (see, for instance, papers by Rundle et ul).65*106 The amylose moiety has a left-handed helical structure 18.65.70.106-109 with six glucose units per turn. In the complex, the diameter of the pitch is 7.91 L%,II~-I'I the outer diameter is 12.97 A,and that of the central cavity is 5 The helical structure is, however, deformed, which makes the amylose helix nonlinear (see Fig. 6).Il2 According to various sources, 10 is the minimum number of turns in the amylose helix which is necessary to provide the appearance of color,'ns-113-116 but a blue color is not necessarily produced in such circumstances.6' Bailey and WhelanMreported that saccharide chains become iodine-stained when they

A.

FIG.6.-The structure of the deformed helix in a solvated state. (Reprinted with permission from J. Hollo and J. Szejtli, Period. Polytech., 2 (1958) 25-37.)

COMPLEXES OF STARCH WITH INORGANIC GUESTS

275

are 18 units long in contrast to earlier'I7 and newer6' findings that the size limit is 30 units. Above 30 units there is a rapid uptake of iodine; however, the uptake is reduced at longer chains approaching 72 (ref. 64) or 100 (ref. 61) glucose units in length. It is suggested that when the degree of polymerization does not exceed 50, surface adsorption cannot be distinguished from the complex formation.l18 According to Bailey and Whelan,@ the interior of the helix has a hydrocarbon-like lining because of the inward-pointing hydrogen atoms of the glucose units. In contrast to this, Hollo and S ~ e j t l i " ~ . assumed "~ that iodine-amylose interactions take place via the hydroxylic groups of the six glucose units per turn (see Fig. 7). Stein and Rundles accepted the involvement of only one hydroxylic group per glucose unit. The first model explains the decreasing affinity of the complex toward enzymic degradation. It involves secondary hydroxylic groups, which are now engaged in holding iodine in the helix. The interiors of the helices are occupied either by iodine molecules or by accompanied iodide anions. There are two iodine atoms per turn when the cavity is saturated with iodine.12' Iodide anions are rather randomly distributed in the peripheral turns of helices (Fig. 8). Odd members on the chain-end bind neither iodine nor iodide According to many a ~ t h o r s , ~ ~ . ~the ' , ' ~13-' .ion ' ~ ~is the complexed unit, with the iodine atoms linearly arran~ed.~'.'1~123~124 The interatomic spacing is 3.10 (Cramer'2s reported 3.05 A). Such spacing provides about 3.9 glucose units per iodine atom. Inasmuch as amylose consists of 200-2000 glucose units, the amylose-13- complex thus incorporates a row of 50 to 500 iodine atoms. According to Cramer and Herbst,'I7 the shortest chain contains 14 iodine atoms, based on the assumption that the shortest blue-staining helix must have 30 to 35 glucose units. Based on the interpretationi26-'2Xof Raman and Mossbauer spectroscopy, the complex ( 13-* 12),, o r even ( Is-),, species are proposed to exist inside the helix, in close agreement with earlier suggestions.lZ9Also, 162-,Is2-, (312 + 21-), and Ilo2-species resulted from theoretical considerationsi3"and experiment^'^' with decreasing concentrations of KI. Among the three later species, 1;- is rather unlikely, as shown by

A

Fiti. 7.--Space pattern of one period of the amylose-iodine complex. (Reprinted with permission from J . Hollo and J. Szejtli, Period. folytech., 2 (1958) 25-37.)

216

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

FIG.S.-Structure of the arnylose-iodine complex. (Reprinted with permission from J. Hollo and J. Szejtli, Brauwissenschuff, 13 (1960) 380-386.)

X-ray s t ~ d i e s ' ~ on ~ - complexes '~~ of iodine with cyclodextrins. By analogy to iodine-cyclomaltoheptaose complexes, ( 12.1-.12)n, (15-)n, and even ( 12.13-.12)nor (17-),, species are also suggested. It is known"' that low concentrations of iodide ions (and low temperatures) favor an increase of the iodine chain length. The amylose-iodine interaction has a dipolar nature, as deduced from a distinct difference between the molecular coefficient of iodine in starch and in nonpolar solvents.'23 The additional stabilization may result from the formation of resonating polyiodine chains at high dipolar interactions. The composition of the total energy of stabilization is shown' in Table VI. This model is oversimplified because it applies solely to the absorption of iodine vapor by dry amylose. On the other hand, Schlamowitz'3s ascribed a predominantly nonpolar form to iodine inside the helix. Studies involving Raman spectroscopy of amylose-iodine complexes suggest a fully resonating polyiodine chain (electron gas model) as the most realistic description of the spectrum.'36Such a model has been proposed by Cramer.'37.'38Charge transfer between iodine atoms and amylose oxygen atoms (as suggested

COMPLEXES OF STARCH WITH INORGANIC GUESTS

211

TABLE VI Interaction Energies between Starch and Iodine" Interaction

Energy, kJ/mol of I2

Repulsion van der Waals attraction Electrostatic attraction Resonance attraction Total energy

-44.1 -119 - 13.0 -112

~

"

64.5

~~~

~~

Reproduced by permission from Stein and Rundle?

by Murakami,"" based on theoretical considerations, and by Ro~sott,'~' based on analysis of IR vibrational spectroscopy) is not possible, as shown by X-ray s t ~ d i e s . ' ~Hydrogen ~ - ' ~ ~ bonds are perhaps an essential part of the interactions."2*'19 Studies carried out in solution provide strong evidence that the helical amylose-iodine complex also exists in such circumstances.' The structure of the iodine-amylose complex has also received theoretical treatment,'42 and a three-dimensional free-electron model was developed for quantum mechanical calculations. Ultraviolet and visible spectra simulated in this manner reached close agreement with experiment observations. The color of iodine-polysaccharide complexes depends on the length of the iodine species within the helix. The large permanent dipole along the axis of the helix resulting from combination of dipoles of individual Dglucose units is consistent with the dipole of this iodine-iodide species entering the amylose cavity. The induced dipole of the latter increases with the length of both partners of the complex. In this manner, iodine binds prefer entially to long amylose chains because of the greater stability of the resultant complex. There is a relation between the length of the helix and the number of complexed iodine and iodide anions. Thus, there is also a relationship between the length of the helix and the color of the c ~ m p l e x . ' ~ "S. ' ~~ a~ n s o n established '~~ that chains having 4 to 6 glucose units do not produce any color, those from 8 to 12 units give a red color (520 nm), and those with 30-35 units display a blue color (600 nm). Table VII gives more detailed assignments of color to the chain length. A summary of all those arguments led to the conclusion that starch blue is a collection of left-handed amylose helices with six glucose units per turn, holding Isunits inside each fraction of the helix. It does not, however, explain the structure of the amylopectin-iodine complex because that complex is branched and apparently has no helical structure. The amylopectin-iodine complex has a purple-red or violet color with an absorption maximum at '03140.141

278

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING TABLE VII Relationship between the Chain Length of Synthetic Polysaccharides, the Color of Their Reaction with Iodine, and the Position of the Absorption Peak in the Visible Spectra of Relevant Complexes'45

Chain Length

Color with Iodine

u p to 5.7 7.4 10.2-12.9 13.3-18.3 20.2-21.2 25-5-29.3 33.1-146.5

None Faint red Red Lavender Purple Blue-purple Blue

Absorption Peak, Lax, nm 500

520 540-560 560-580 580 600

approximately 540 nm, regardless of both the origin of the polysaccharide and the degree of b r a n ~ h i n g . UV ' ~ ~ spectroscopy studies of dextrins and amylopectin suggest that the outer branches of amylopectin are composed of approximately 18 glucose units and that the inner branches consist of about 10 subunits.'45Mould'22 postulated that, in red-staining polysaccharides, the 13- species is responsible for the color because of the weak bonding of iodine to the polysaccharide chain. This low binding power (but not capacity) is attributed to disruption of helix formation, by the large number of branch points.I4' Higginb~tharn'~' found that the iodine-binding capacities of amylose and amylopectin are practically identical. Hence, another mechanism governs the bonding of iodine to amylopectin. He suggested that outer branches may coil into short helices under the influence of iodine. Such helices complex I2 and 13- species. Surface adsorption of those species is, however, also involved. According to Gilbert and Mari~tt,'~' red staining is due to the adsorption of eight atoms of iodine and one I- ion per molecule of the linear polysaccharide structure. Hydrogen bonds between amylopectin and iodine may be essential in such a c a ~ e . ~ ~ ' , ' ~ ' 8. The Mechanism of Complex Formation

The pathway for the formation of the amylose-iodine complex is well recognized, at least when aqueous solutions of KI and iodine are used. Relevant studies are lacking on the formation of the complexes between iodine vapor and both amylose and amylopectin. Thus, randomly coiled amylose binds 13- ions, and this interaction is responsible for the helical structure of amylose. Helical amylose arrests iodine and further 13- anions, a process which is cooperative. If the filling of one helix commences, then the filling of another helix proceeds once the former helix is full. The longest available helix has priority in the uptake

COMPLEXES OF STARCH WITH INORGANIC GUESTS

279

of iodine. After the uptake by the longest helix is completed, the completion of the next one begins. According to the results of Cesario and Brant,Il3 the limiting uptake expressed by the ratio of [Ij-]bound/{[12]bound+[13-]bound} reaches 0.3 ? 0.11. Additional polarization of the system can be caused by interactions between iodine molecules that are within the helix and/or adsorbed to the exterior surface of the helix and iodine molecules outside of this complex: (amylose . . . 1-1) + 1-1 F? (amylose . . . I . . . I . . . I)-I+. This process with iodine vapor is assumed to be responsible for the formation of the blue complex with starch without KI added.Is2 During the 1920s a suggestion was made'53-'55 that iodine is adsorbed by starch in two consecutive steps. The first step is rapid and is followed by slow sorption; equilibrium is not reached in most cases. The rate of reaction of iodine with starch was first rneasuredIs6 in 1939. The results depend on the variety of starch and on the amylose-to-amylopectin ratio, as illustrated by Huebner and Venkatararnad9 (Fig. 9). The rate of uptake of iodine differs in both consecutive steps, according to the origin of the starch. These differences can, moreover, be attributed to the different affinities of those starches to retrogradation. As shown by Hollo and S ~ e j t l i , ' ~ ~absorption -''~ of iodine decreases as a function of time and is also dependent on pH (Fig. 10). The binding capacity of iodine by starch was studied by spectrophotometric, potentiometric, amperometric, and rheological methods. A sharp increase in the viscosity of starch solutions occurred after the amylose helix

t

Days

FIG.9.-Effect of time (in days) on the amount of iodine adsorbed by 3 g of maize (M), rice (R), sago (S), tapioca (T), and wheat (W) starch. (Based on the data of Huebner and Venkataraman.")

280

PlOTR TOMASIK AND CHRISTOPHER H. SCHILLING

4

B

12

16 20 24 Time, h

h

FIG.lO.-Effect of time (in h) and pH on the iodine uptake by amylose at 28°C. The effcct is expressed as change of absorption of I2 (in %) with respect to the point of origin. (Reprinted with permission from J. Hollo and J. Szejtli, Przem. Spoz., (1957) 429-433.)

reached saturation. The process of helix saturation does not affect the viscosity. The second step, which appears to be adsorption of iodine on the surface, is responsible for the observed increase of viscosity due to bridging of individual helices by i ~ d i n e . ~ ~ ~ , ' ~ ~ , ' ~ " In spectroscopy studies it should be remembered that the LangmuirPerrin absorption law is obeyed, whereas the Beer-Lambert law is Increasing the proportion of iodine is accompanied by an increase in absorption intensity and a red shift of the absorption band, whereas increasing the proportion of KI decreases the intensity and shifts absorption toward the blue end. Another authory1observed the opposite effect of the KI concentration on the intensity of the absorption bands. When the concentrations of free iodine is farily high, amylopectin binds as much iodine as does amylose.16yThe effects of pH and temperature have been studied by S ~ e j t l i ' and ~ ~ ) Hatch.I7' The intensity of the 625-nm band (the longest wavelength band) decreased as the pH and temperature increased (see Fig. 11). Among the methods listed here, the amperometric determination has evoked the most i n t e r e ~ t . ' ~ ~ . ' ~ Potentiometric ,'~~-'~' mea~urements~~~.~~~* also confirm the findings of these methods, although the equilibrium concentrations of free iodine are lower by one order of magnitude than those determined by photometric titration. For the reaction Amylose

+ yI- + x12 = Amylose x12yI-,

the enthalpy, AH, is determined to be -46.8 kJ/m01.'~~ For the reaction Arnylose + nI-

+ n12 = Amylose nI2nI

,

COMPLEXES OF STARCH WITH INORGANIC GUESTS

281

w

39.0

10 1

2

3

4

5 PH

6

FIG. 1 I.-Effect of pH and temperature ( T ) on the formation of the amylose-iodine complex, expressed as the change (in %) of the relative extinction of the band measured at 625 nm. (Reprinted with permission from J. Hollo and J. Szejtli, Przem. Spoz., (1957) 429-433.)

A H = -64.9 kcJ/m01,""*~ and the equilibrium constant K = 1/[12] = -65.7 kJ/mol.IXs Am perometric methods indicated AH = -7.20 kcJ/ mol.' 1')~1s8-1h0~1Xh Spectrophotometric methods indicated values of AH ranging from -41 kJ/mol'*' through 53.6, (ref. 188) 16.6 (ref. 188) to 87.0 kJ/ mol. (refs. 91, 184). Calorimetric methods produced values of -70.3 (ref. 189) and 71.6 (ref. 113) kJ/mol. Approximately 10-20% of the overall value of AH (that is -6.7 to -12 kJ/mol) is attributed to nearest-neighbor interactions.I" More precise thermodynamic parameters are given by Yamamoto etaf.,"' who reported data for both steps of the complex formation. The temperature effect of the second cooperative step of the reaction is equal to zero, which suggests that this step is controlled by entropy and not by enthalpy. The free energy of formation of the iodine complex with amylose and amylopectin was estimated at 25 and 21 kJ/mol, respectively."* The stability constant at 25"CI9' is of the order of loh. The differences in AH presented here are attributable to two factors: (1) the character of the analytical methods employed, and (2) the KI concentration, which affects the position of the triiodide-iodine equilibrium because of the uptake of the constant ratio of the iodine and triiodide molecules in the ~ o m p l e x . " ~ The following diagrams show the effect of iodine concentration on the binding capacity of starch (Fig. 12), the effect of KI concentration (Fig. 13), the effect of temperature (Fig. 14), and the effects of the extent of

282

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

1

2

3

4

5

Pn 12 FIG.12.-The iodine-binding capacity (IBC) of starch (in %) as a function of the concentration of free molecular iodine (in mol). (Reprinted with permission from J. Hollo and J. Szejtli, Bruuwissenschafi, 13 (1960) 348-352.)

hydrolysis of amylose (the effect of the length of the amylose chain) (Fig. 15). According to Adkins and G r e e n ~ o o d ,the ' ~ ~effect of low temperature can only be observed in the case of short-chain amylomaize starch (see references 169, 196, and 197) for discussions of the temperature effects). Circular-dichroism (CD) analysis revealed three steps in the formation of the blue complex. The first step is shown by the shoulder at 480 nm in the UV-VIS absorption spectrum and is due to formation of the complex of the amylose fraction having a degree of polymerization (DP) from 10 to 30. The second step is the development of color from 13- ions with amylose of DP 30 to 100. The third step, which is the development of a deep-blue color, is associated with the shallowing of the dual CD band for high-DP

-s

N

20 15

10

0

1

2

3

4

n KI

FIG.13.--lodine-binding capacity (IBC) of amylose as the function of the concentration of 1- ions (in mol of KI). (Reprinted with permission from J. Hollo and J. Szejtli, Bruuwissenschufl, 13 (1960) 348-352.)

COMPLEXES OF STARCH WITH INORGANIC GUESTS

20

30

40

283

50 60 t em pemture.O C

FIG.14.-Variation of the absorbance at 600 nm of the amylose-iodine complex as the function of temperature. Crosses: measurements on heating; circles: measurements on cooling. (Reprinted with permission from Nature, 197, pp. 898-899, copyright 1963 Macmillan Magazines Limited.)

amyloses at high concentrations of iodine. Skewed ions located in the knot portions interact in the associated helices of the aggregate.61 The formation of the starch-iodine complex is affected by alcohols. This effect is interpreted as the result of the isolation of polyiodide chains inside the amylose helices as molecules of alcohol also occupy their i n t e r i o ~ - . " ~ * ' ~ ~

10

20

30

AE

FIG.15.-Variation of the iodine-binding capacity of amylose and the iodine concentration expressed in the weight of iodine as a function of the degree of hydrolysis ( A E ) . (Reprinted with permission from J . Hollo and J. Szejtli, Brauwissenschafr, 13 (1960) 380-386.)

284

PlOTR TOMASIK AND CHRISTOPHER H. SCHILLING

When whole starch granules react with iodine or an iodine-iodide mixture, the structure of the granule changes. Iodine is more readily bound by the internal part of the granule than by the external part.'99 A similar effect is observed when granules react with zinc chloride iodide anions.2Mx' 9. Properties of the Iodine Complex

a. Physical Properties-(i) Ultraviolet and Visible SpectroscopyAbsorption spectroscopy in the region of 200-700 nm played a crucial role in understanding the structure of iodine complexes with starch and its components, as well as the mechanism of the complex formation. Investigations by Rundle et ~ l . , " S~ ~ a n s o n , ' ~Ono ' et ~ l . , ~Bailey ' and Whelan," and Kerr et d 2 0 1 revealed that the wavelength of maximum absorption of the amylose-iodine complex is related to the amylose chain length. This shift, which obviously has its effect on the color observed, is interpreted as the result of the state of aggregation of the complex.202Again, this property is governed by the average length of the uninterrupted amylose helices and the degree of crystalline order.203These can be primary factors affecting the spectra. Mokhnach and Rusakova" have shown that amylose-iodine and also starch-iodine complexes absorb at 226, 288-290, 344-360, and 585620 nm. The first band appears only when iodine is added to the solution simultaneously with KI, and it is absent when only iodine is added. The longest-wavelength absorption may be indicative of the molecular size of the carbohydrate portion of the complex, as demonstratedlMin Table VIII. Spectra of iodine-amylopectin complexes were measured by Archibald et The UV absorption spectrum of the starch-iodine complex is shown

TABLE VIII Relationship between the Molecular Size of Amylose and the Spectral Properties of Its Blue Complex with Iodine1& Molecular Size"

Amylose

A,,,, nm

~

Potato Tapioca Lily Corn Crystalline Synthetic Arnylodextrin ~~

&max ~~

500 450 310 250 175 85 44

628 625 622 618 605 590 580 ~~~

Number of glucose residues per molecule.

43,000 4 1,600 41,400 40.400 40,100 32,900 25,400

COMPLEXES OF STARCH WITH INORGANIC GUESTS

F

6.0 '

2

285

5.0.

E

OJ 4 . 0 .

3.0. 2.0.

i n

1 .o

in Fig. 16. The variation of the spectrum is attributed to the varying starchto-iodine ratio.204It had earlier been observed by Gilbert and M a r i ~ t t ' ~ ~ that the amylose complex with iodine is metastable and undergoes a physical change as a function of time. Pfannemuller and Z i e g a ~ t 'made ~ ~ similar observations by UV-VIS absorption spectroscopy (Fig. 17). 606

I X

0

E

u)

300

400

500

600

700

800

A ,nm FIG.17.-Absorption spectra of aqueous solutions of I2 (A) and amylose with 190 glucose units after the addition of iodine after 5,30,60, 150, and 270 min (B through F, respectively), and the complex of the same amylose with the 12-KI complex (G). (Reprinted with permission from B. Pfannemueller and G. Ziegast, Sfaerke, 35 (1983) 7-11.)

286

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

the IR spectra of (ii) Infrared Spectroscopy.-According to amylose and its blue complex are identical. Nevertheless, Greenwood and RossottiZo6found two small differences between these spectra. The spectrum of the complex exhibits two small peaks at 1101 and 1052 cm-' (Fig. 18).By analogy to the spectra of iodine in ethers (diethyl ether, 1,4-dioxane, tetrahydrofuran), where peaks appear in that region with assignment to the -I coordination band, these peaks in the spectrum of the amylose-iodine complex are ascribed to such interactions. These suggestions were presented subsequently by M~rakami,'~' and they were rejected by Noltenmeyer and Saenger.'32.'33Thus, this band assignment is doubtful. Assuming this type of interaction, the authorszMproposed a boatlike conformation of glucose units in the helix, but Murakami expressed a contradictory opinion in this re~pect.~" (iii) Raman Spectroscopy.-These are four characteristic maxima (162, 112,52,and 24 cm-I) in the Raman spectrum of the amylose-iodine complex (Fig. 19).'28~131~1"~142~208 The intensities and structures of individual peaks (shoulders) depend to a certain extent on the degree of polymerization of amylose, as well as on whether the complex was prepared from amylose and iodine or amylose and on 12-KI mixture. Despite thorough analysis of the spectra,I3' it was not possible to distinguish between stretching frequencies and bending frequencies in such units as 13- * I2 . 13- or 13- I2 * Iz . 13-, nor was it feasible to distinguish between possible iodine chain-units

1250

1000

750 Clli'

FIG.K-Infrared absorption spectrum of the amylose-iodine complex. [From Greenwood and Rosotti?" Copyright 0 1958 John Wiley & Sons. Reprinted by permission of John Wiley & Sons, Inc.]

COMPLEXES OF STARCH WITH INORGANIC GUESTS

287

164

0

300 cml

FIG.19.-Resonance Raman spectrum of the amylose (DP 25)-iodine complex. (Reprinted with permission from B. Pfannemueller and G. Ziegast, Stuerke, 35 (1983) 7-11.)

themselves. The existence of Is- units seems to be most likely. The opinion'36 was also expressed that there is a fully resonating polyiodine chain in the amylose helix instead of a polyiodine chain composed of discrete iodine and iodide species forming regularly dislocated subunits therein. (iv) Mossbauer Spectroscopy.-Analysis of the Mossbauer spectrum of the starch-iodine complex (Fig. 20 and Table IX) points to three unequivalent iodine sites in approximate relative populations of 2:2:1. In this manner the Is- is shown to be the predominant polyiodide unit inside the amylose helix."'

(v) Electron Resonance Spectroscopy.-In 1961, Bersohn and Isenberg"' observed a weak electron resonance in the amylose-iodine complex. Based on this observation, these authors deduced that if atoms of iodine in the chain are mutually covalently bonded, the band of the 5ps state is only partially filled. This would result in metallic properties, including weak paramagnetism and electronic conductivity. The fundamentals of this conclusion met with criticismz1"because the results of the earlier authorszw

-20.0 -10.0 a0

iao

20.0

mm/sec

FIG.20.-The iodine-129 Mossbauer spectrum of the starch-iodine complex. [Reprinted ' ~ ~ (1980) American Chemical Society.] with permission from Teitelbaum et ~ 1 . Copyright

288

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING TABLEIX '*'I Mossbauer Parameters for the Amylose-Iodine ComplexUS Site 1

a, mmlsec (versus ZnTe) e2qQ, MHz (for 12')1) r, mm/sec (line width) Relative population

1.22

- 1743 1.14 1.9

Site 2 8, mmlsec e2qQ, MHz r, mm/sec Relative population

0.53 -1187 2.13 1.8

d, mm/sec e2qQ, MHz r. mm/sec Relative population

-842 1.08

Site 3 0.14

1.o

could not be repeated when the samples were stored in the dark. Exposure to sunlight was evidently the only reason the ESR spectra could be recorded at all. Although Insberg and Bersohn211accepted the criticism, they did not reject their one-dimensional model for iodine inside the amylose activity. Their results suggest the possibility of a photochemical reaction of the complex, which can be either iodination or oxidation. Two years later, P e t i ~ o l a s demonstrated '~~ that the former observation could be done to moisture present in the sample. (vi) 'H and I3C Nuclear Magnetic Resonance Spectroscopy.-The I3C NMR spectrum depends on the type of starch (amylose-to-amylopectin ratio) and is associated with the numbers of carbon atoms in the branching points and thermal glucose units. Tables X and XI present I3Cspin-lattice relaxation times ( T I , $ )and nuclear Overhauser enhancement (n.0.e) for I3C nuclei of starches of various origins. Figure 21 shows IH NMR spectra of amylose and a high-amylopectin waxy sorghum starch. The amount of iodine complexed by starch of various origins depends on the same factors as the NMR spectra. There are satisfactory linear correlations between the iodine-binding capacity and the percentage of terminal glucose units of starch. The latter could be calculated from the intensities of the proton and carbon chemical shifts.81 (vii) Dichroism.-The flow of solutions of the starch-iodine complex exhibits dichroism.212This phenomenon is associated with the difference

COMPLEXES OF STARCH WITH INORGANIC GUESTS

289

TABLE X I3C NMR Spin-Lattice Relaxation Times for Starch of Various Origins" Relaxation Times, Sec Atom

Signals, ppm

Sorghum

Wheat

Potato

Corn

c-1

100.4" 100.2 100.1 99.9h 79.3 79.2 79.1 79.0 78.9" 70.4" 72.5" 72.0h 61.O"

0.29 0.22 0.19 0.19 0.19 0.23

0.30 0.19 0.18 0.18 0.18 0.18 0.20 0.20 0.20 0.23 0.27 0.20 0.12

0.28 0.20 0.18 0.18 0.19 0.22 0.21 0.17 0.20 0.30 0.25 0.19 0.12

0.25 0.22 0.15 0.19

c-4

c-2 C-6

0.19 0.20 0.28 0.27 0.21 0.12

c

0.15

0.17 0.20 0.23 0.26 0.20 0.12

"The signal is attributed to the glycosyl end group. *The signal is attributed to the glycosyl groups of the main chains. ' The signal is not adequately resolved.

in the absorption of light photons, with the electric vectors being parallel and normal to the flow lines. Dichroism of flow indicates the preference of absorption of photons with the electric vector parallel to the flow. Dichroism in this particular case requires parallelism of the long axes of the iodine molecules and the starch-iodine complex. Dichroism is readily observed

TABLE XI Values of Nuclear Overhauser Effect for 'jC Nuclei of Starch of Various Originss1 Nuclear Overhauser Effect Starch

C-1"

C-lb

C-4"

C-4b

C-6"

C-6'

Sorghum' Wheat Potato Corn"

2.15 2.22 2.58 1.99

1.69 1.76 1.66 1.65

1.99 1.91 2.11 2.35

1.71 I .74 1.71 1.71

2.27 1.76 2.52 2.37

1.84

The values for the glycosyl end groups.

'The values for the glycosyl groups of the main chain. ' Waxy starch. " High-amylose

starch.

1.92 1.82 1.87

290

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

P Pm FIG.21.-Partial 'H NMR spectra (300 MHz) of amylose (A) and waxy-sorghum starch (B) in MezSO-d6 at 23°C. (From Peng and Perlin.8')

in the case of iodine complexes of starch and amylose. A small amount of dichroism can be noted for red-staining starches, waxy maize starch, and glutinous rice starch. Starch stained with iodine, with subsequent removal of iodine from the sample, exhibits no dichroism. Hence, the dichroism of flow of iodine-stained solutions is a function of the size of the

(viii) Circular Dichroism and Optical Rotatory Dispersion.-Starch and complexes of iodine with starch, amylose, and amylopectin, are amendable to study by optical rotatory dispersion and circular d i ~ h r o i s r n , 6 ~ *be'~"~~~~ cause these polysaccharides exhibit a positive induced Cotton effect in the region of the absorption maximum (545 nm). Figures 22-25 show the UV-VIS absorption spectra, rotatory dispersion, and circular dichroism spectra of starch-, amylose-, and amylopectin-iodine complexes. The rotatory power and extinctions at 600 and 445 nm depend on the iodineto-carbohydrate ratio, as shown in Figs. 25 and 26. At constant extinction, the optical rotation of the complexes may increase with time, although it is not a general property. Both the absorption spectrum and the optical rotation are sensitive to heat and certain additives, because of changes in structure of the complexes.

(ix) X-Ray Diffraction.-Powder X-ray diffraction played a crucial role in clarifying the structure of starch-iodine complexes (Table XII)!8 The amylose-iodine complex forms a hexagonal unit cell with a, = 12.97, c, = 7.91, and dlM)= 11.23 A. (ref. 72)

COMPLEXES OF STARCH WITH INORGANIC GUESTS

291

AE

3 2 1

0

300

LOO

600

500

h ,nm FIG.22.-Absorption (-), ORD (- - -), CD (-..-) spectra of aqueous solutions of soluble starch ( a ) K13 ( b ) , and the starch-iodine complex (c). (Reprinted with permission from R. C. Schulz, R. Wolf, and H. Mayerhoefer, Kolloid-Z., Z. Polyrn., 227 (1968) 65-72.)

1500 1000

q:o 2000

II

500

1000

I

350 400

5qO"

600

700

'

0

FIG.23.-Absorption (-) and ORD spectra of the amylose-iodine spectrum.(Reprinted with permission from R. C. Schulz, R. Wolf, and H. Mayerhoefer, Kolloid-Z., Z. Polym., 227 (1968) 65-72.)

292

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

. 1500 -

2500

500

1

-500

hnm

--0.4

FIG.24.-Absorption (-), ORD (- - -), and CD (-.-) spectra of amylopectin (API) and the amylopectin-iodine complex. (Reprinted with permission from R. C. Schulz, R. Wolf, and H. Mayerhoefer, Kolloid-Z., Z. Polym., 227 (1968) 65-72.)

(x) Rheo1ogy.-Rheological studies complemented the amperometric analysis of the structure of starch-iodine complexes."2~"yThis method was refined by Liang et and served in conformational studies of those complexes. The authors sought relationships between intrinsic viscosity [ 771 and the concentration of iodine added to polysaccharides. Such a relationship displays a sigmoidal pattern, as shown in Fig. 27. The pronounced increase of 1771 on complexation with iodine is caused by a stiffening of the helix that is not accompanied by any conformational changes. Iodine does not affect the shape and/or extension of the chain in space. The complex-

4ooov 2000

01 0

I

0.05

01

I

0.15

0.2

0.25

12 . 9 / L

FIG.25.-The shift of the maximum of the specific rotation of the starch-iodine complex as the function of the concentration (c) of iodine (in 12-C6H1005, mollmol). (Reprinted with permission from R. C. Schulz, R. Wolf, and H. Mayerhoefer, Kolloid-Z., Z. Polym., 227 (1968) 65-72.)

COMPLEXES OF STARCH WITH INORGANIC GUESTS

293

*Oo0 05.1000

/--------

0,4

FIG.26.-Specitic rotation (- - -) and extinction coefficient (-) of the amylose-iodine complex as the function of the concentration (c) of iodine. (Reprinted with permission from R. C. Schulz, R. Wolf, and H. Mayerhoefer, Kolloid-Z., Z. Polym., 227 (1968) 65-72.)

ation also reduces the sensitivity of [v]to changes in temperature, as a rigid particle is less able to dissipate thermal kinetic energy than a flexible one. b. Chemical Properties.-Little is known regarding the effects of the iodine chain inside the amylose helix on the reactivity of that helix, and the effects of adsorbed iodine molecules on the reactivity of polysaccharides in general. Also, heating of the complex in aqueous solution causes its decomposition. This is due to the replacement of iodine inside of the helix by water .27.2 5-2 I7 Th e thermal decolorizing effect is due to the decrease of the length of the amylose helix2Is and not, as previously suggested, to the evaporation of iodine.21yIn contrast, the influence of iodine on chemical reactivity and its effect on the enzymic degradation of starch is well known.l5 Complexation of starch with iodine increases its resistance to enzymic degradation, as shown in Fig. 28. It is known that ultraviolet light affects the complex, both in the solid state and in aqueous solution. Complexes undergo gradual decolorization as a result of deterioration of the helix and reaction of the iodine-iodide complex anion with water to produce HI.220-222 It has also been shown209-21' that ordinary room lighting in the presence of atmospheric oxygen affects the complex by oxidation, but this process has not been studied in detail. Both X-rays and ultraviolet light cause similar disruption of the complex, but the process is faster with the former.223Radon has a similar effect.224 Boric acid is known to complex starch (see Section IV), and the same complexation takes place with the starch-iodine complexes. Figure 29 diagrams the assumed position of attached boric acid.lSyAs with starch, starch blue is capable of sorbing some dyes (Acridine Orange, Methylene Blue, and 1,9-dimethyl-rnethylene blue).22sThis phenomenon is discussed in more detail in the accompanying article (p. 345).

'

294

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

XI1 TABLE Results of X-Ray Powder Diffraction of the Amylose-Iodine Complex" Sin2 MA2 Hexagonal Indices

Observed

Calculated

100

0.001965 .005937"

0.001979 .005912 .005965 ,007916 .009925 .01192 .01386 .01782* .01797 .01786 .02189 .02193 .02375 .02391 .02573 .02976 .02985 .03162 .03767 .0415gh .04166 ,04174 .04558 ,04767 .04950 ,05344 .05542 ,06137 .07126 .07324

llOb

101 200 111 201 210 300b 211 102 301 112 220h 202 310 311 212 400 320 410" 321 312 411 402 500 330 420 510 600 430

.007922 .009955 .01158 .01384 .01781 .02182 .0237Sh .02573 .02974 ,03178 .03775

.04155 .04551 ,04763 .05360 .05549 ,06165 .07114 ,07310

Intensities

vs S S M VM

vw vs S

ww M MS

vw W M

M

vvw vvw nil

vw vw

vw vw

vw

Reproduced by permission from Rundle and Only the reflection (h,hzO) should be intense enough to influence the position of the line. I,

Iodine can be removed from the complex by means of thiosulfate ions; the activation energy of this fast reaction is 8 kcal/mo1.226 Several organic compounds either change the color of the complex or eliminate color altogether. Color disappears under treatment with egg albumen and several proteins, an effect caused by the formation of inclusion complexes with the proteins. Among a-amino acids, only tyrosine exhibited such behavior. Furfural also decomposes the blue complex and epinephrine

COMPLEXES OF STARCH WITH INORGANIC GUESTS

295

0.4-

40

0

8.0 12.0 16.0 20.0 rnV

FIG.27.-The relationship between the intrinsic viscosity (7)and concentration of 12 added to starch solution. (Reprinted with permission from Joan-Nan Liang, C. J. Knauss, and R. R. Myers, Rheol. Acra, 13 (1974) 740-744.)

5

10

15

20 X ,%

FIG. 28.-The variation of the iodine binding capacity of starch in the course of the enzymic hydrolysis of starch and the starch-iodine complex. (Reprinted with permission from J. Hollo and J. Szejtli, Brouwissenschufi, 13 (1960) 380-386.)

FIG.29.-The mode of iodine binding in the amylopectin-boric acid complex. (Reprinted with permission from J. Hollo and J. Szejtli, Ferre. Seifen. Anschtrichminel, 59 (1957) 94-98.)

296

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

instantly changes the color from blue to pink.” Certain corrections may be required in the quantitative determination of starch in the presence of such corn pound^.^^^^"^^^^^ 10. Applications of the Complexation and the Complex

a. Analytics.-Use of the reaction in iodometry is well known (see, for instance, reference~’’~-~~~, and in this section, only a few less-known facts and more sophisticated applications will be cited. Some authors have recommended the use of Cd12 instead of KI as the source of the 13- complex ion, and ZnC12.238 as well as cadmium Carboxylic acids separated by starch-impregnated paper chromatography can be visibly detected by using the 1-103- solution. The sensitivity depends on the dissocation constants of the acids. Addition of CaCI2 increases the ~ensitivity.’~’Microgram-level determination of thiosulfates by paper chromatography has also been reported. In this case, the chromatographic strip is impregnated with the starch-iodine complex.240 A method of determining airborne iodine has also been rep0rted.2~’ Here, iodine is absorbed into 5% aqueous KI and spectrophotometrically determined at 590 nm in the form of its complex with starch. This method is selective with respect to bromine and chlorine, and the sensitivity of this method is 0.25 mg of I2 per m3 of air. The concentration of the I3lI isotope in water can be determined by a method involving isotope exchange in the starch-iodine complex.242Flow-injection determination of ascorbic acid (0.1-40 mg/mL) has been proposed.243Iodine is generated in the flow system as 13-ions, which are in turn exposed to starch to produce a steady signal at 350 and 580 nm. Ascorbic acid provides inversed maxima which are measured. This method is recommended for analysis of ascorbic acid in fruit juice, jam, and vitamin-C preparations. Use of the blue complex has also been reported for determination of sodium dichloroisocyanurate in air.244Obviously the blue reaction is applicable in the determination of amylose, amylopectin, and s t a r ~ h ? ~ “as ’ ~well ~ as modified starchesa245,25%2SS Since the result of the starch reaction depends on the type of starch, the blue reaction is suitable for the characterization of different varieties of starchy materials,76.77.105.162,256-275 and a special coloristic scale has been developed for industrial purposes.276A negative correlation was observed257 between the color density of the complex and the stickness of cooked starchy material. The blue reaction is very useful in determining the amylose-amylopectin composition of ~ t a r c h , 6 ’ , ~ and ~ ~ +in~ ~ controlling ’ of the effect of mechanochemical and enzymic treatment and fractionation of s t a r ~ h ~ ~ - ~ ~ ~ ~

COMPLEXES OF STARCH WITH INORGANIC GUESTS

291

and staining enzymes.2yo-2y3 The usefulness of the starch-iodine reactions in the study of retrogradation, and was demonstrated by Hollo et u1.294*29s an investigation of the nature of various starch inclusion complexes has been reported by Rutschmann and S ~ l m sSzejtli . ~ ~ et~ul. published determination of the degree of polymerization of amylose, based on its reaction with iodine.297The use of a starch-iodine complex as a histochemical reagent has also been reported.298 b. Amylose Fractionation and Separation.-Fractionation of amylose achieved based on the sequence of iodine uptake by amylose, a process that is dependent on the length of its helix.263~2yy~30" Electrophoretic separation is described by Mould.'22

c. Concentration and Extraction of Iodine.-Attempts to utilize starch to extract iodine from dilute aqueous solutions have been made by Magidson,3"' and the applicability of this method for use on a large scale has been discussed. There is a French patent on iodine extraction from seaweed using starch.'02 d. BiologicallyActive Preparations.-Iodine is well known as a powerful disinfectingand antiseptic agent. It may be possible to attenuate this activity by iodine complexation with starch. It is reported that a mixture of soluble starch (25 g) and 1:lOO iodine-iodide combination (50 cm3)in boiling water (1 dm3)does not irritate tissues, does not harm clothing, and is stable. It also kills streptococcic, pyocyanic, and colic bacteria.3o3Another preparation for such purposes consists of starch, glycerol, water, and iodine.304Other modifications have also been p r o p o ~ e d .Among ~ ~ ~ , starch, ~ ~ ~ amylose, and amylopectin, the first two are superior carriers for iodine. The bacteriostatic properties against gram-positive and gram-negative bacteria are manifested at concentrations of 2.5-20 g/cm3 after 15 min of e x p o s ~ r e . ~ ~ ~ - ~ ' ~ Use of the starch-iodine complex has been reported for the disinfection of wounds and for the artificial insemination of animal^.^" Food containers may also be disinfected with this complex.311Uses of the starch-iodine complex in the iodization of food3'2,313 and ruminant fodde9l4 have also been described. This complex has been found effective in the storage preservation of cabbage and carrots,315potatoes?16 and apples?" The addition of 0.0005 to 0.005% of the complex to bee honey also improves its properties; it was reported that the application of a 1%aqueous solution of the complex for spraying bee houses increased the yield of honey.318 Intragastric injection of the complex (49 mg/dm3 of iodine content) to rats is reported to provide slight radioprotection from gamma rays (5 Gy at 1.8 Gy/min or 4.19 Gy at 1.235 G ~ / m i n ) . ~AI ~microbial fabric that

298

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

contains in its fibers a small quantity of starch-iodine complex has also been patented.’2” e. Miscellaneous Applications.-The starch-iodine complex was proposed as an additive for the production of special copying paper.”’ Iraqi scientists322demonstrated that this complex improves the thermal efficiency of liquid solar collectors and is more effective than potassium chromate, potassium, permanganate, and Indian ink additives.

111. STARCH-WATER COMPLEXES

1. Introduction There are several theoretical and technological problems associated with the presence of water in star~h.’~’ The amount of water in starch determines its nutritive value and functional properties. Knowledge of the amount of water is essential in selecting the mode of processing starch by drying, moisturizing (as in dough production), thermal treatment, extrusion, molding, and hydrolysis. Water also affects the stability of starch during storage, particularly with respect to mold formation (starch and cereals with 13-17% humidity are moldproof when stored324at 20°C),dusting, and dust explosivity. Water causes corrosion of the metal of silos and transporters. The possibility of molding with moist starch increases the risk of corrosion by mold slime.325As demonstrated by Muetgeert et uL,326 water in starch determines its chemical reactivity; anhydrous starch is unreactive. The reactivity of starch decreases with drying, and this is reversible when the starch is remoisturized. Reactivity is readily restored upon contact with acetic acid. Regarding the hydration of starch, two points must be distinguished. The first concerns saturation of starch with water (that is, the water-binding capacity of starch), a value that is usually related to water uptake and loss (sorption-desorption) from and to the atmosphere. This is a significant technological problem, because the water concentration varies according to the origin of starch and the temperature. Below the freezing point, it is reported that the starch matrix holds up to 46.5% of starch.327Another concern is that the estimated value of the water content depends to a certain extent on the method of its determination. Table XI11 presents estimates by many authors. It should be mentioned that the first studies of water in starch are dated” as early as 1834. The second point concerns water that is usually held by “natural” starch, that is, a state that can be considered as the natural starch-water inclusion complex. In this case also, the concentration of such water depends on the same factors as those just mentioned. Corresponding data are given in Table XIV.

COMPLEXES OF STARCH WITH INORGANIC GUESTS

299

TABLE XI11 Water Saturation Capacities (YO)for Starch of Different Origins at Room Temperature" Corn Potato Rice Sweet potato Tapioca Wheat Waxy corn

19.55-28.7 20.9-33.7 20.8-26.8

18.7-31.63

(39.9) (50.9) (40.5) (43.5) (42.4) (39.9) (51.6)

" The values recalculated on a dry starch basis are given in parentheses. Below the freezing point, the starch matrix of potato starch holds up to 46.2%of water. The estimation for the starch matrix at 20°C. given by the same author?20 is 35.5%.

Reviews on starch hydration were published by Schierbaum3*' in 1960 and by Nara et al.329in 1968 and (ref. 330) 1981. The first scientific approaches were based on an assumption that water in starch is held by sorption. R a k o ~ s k i ~observed ~I-~~~ hysteresis in measurements of the uptake and loss of humidity by solid starch; other authors334-336 subsequently confirmed the S-shape of the isotherms. At the time of these publications, more detailed knowledge of the structure of starch granules was not available, nor was the helical structure of amylose recognized. Nevertheless, Malfitano and M o s ~ h k o f described f~~~ part of the water residing in starch as the water of hydration and constitutional water. In this manner, they presented the idea of different fractions of water in starch. Several authors, using various techniques, confirmed these observations. Various methods have been proposed for determining the localization of water in starch materials. In the work of van der Haeve et ~ l . , ~a ~ ' portion of the water was identified as a constitutional water of micelles, and TABLE XIV Water Contents (YO)in Natural (Native) Starch of Various Origins Arrowroot Corn Potato Rice Sago Tapioca Wheat

11.37-16.50 11.61-16.00 13.34-22.42 13.71 (average) 12.80-18.83 11.37-16.50 10.52-16.10

300

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

same^^^' suggested capillaries as the location of water molecules. Further reported three water molecules bonded to one glucose unit of starch, although later studies have reported one and two bonded water molecules per glucose nit.^^^*^^^

2. The Status of Water in Starch The first essential observation in the middle of last century345distinguished two types of water absorbed from the atmosphere (the equilibrium water). However, R a k o ~ s k i ~performed ~ l - ~ ~ ~ kinetic studies of the drying of starch and observed that two-thirds of the total water in starch was desorbed during the first 24 hs, and it required another 2 weeks to remove the remaining water. In this 2-week period, 98%of this content desorbed in the first week, whereas the remaining water was desorbed during the second week. Infrared radiation studies on the dehydration of potato starch346led to the conclusion that at least four different types of water are held in starch. Further investigation^^^' validated this conclusion, but only in the case of potato starch. There are three well-observed transition points on a chart of weight loss as a function of time during the infrared drying of starch. In contrast, cereal starches exhibit only two transition points. The type of dehydration of gelatinized (swollen) starch is reflected by a curve of similar shape, but with the transition points that are not recognizable (see Fig. 30). Nevertheless, the authors distinguished only two types of water, namely, capillary water (between A and B transition points) and the water of adsorption (from the B transition point up to the end of

4p

At

HzO.’/O

FIG.30.-The course of starch dehydration (in dgldt, where g is weight and r is time) for potato (P), wheat (W), and rice (R) starch. (From Schierbaum and Taeufel.”’)

COMPLEXES OF STARCH WITH INORGANIC GUESTS

301

the diagram). The same conclusion can be reached based on the agreement of the sorption-desorption curves with the Freundlich isotherm348 a =

(y

pllrz

(4

where a = x/m is the total adsorbed water per unit weight of starch, p is the partial pressure of water vapor, a is an adsorption constant, and l / n is the adsorption exponent. Chapek et a1.34y*3‘0 pointed out that, among the two types of water of hydration, a significant major proportion of the water is weakly bound, weakly oriented, or osmotic. Its heat of adsorption is approximately 2 kcal/ mol. Later s t ~ d i e s ~with ~ l the , ~ ~NMR ~ spin-echo technique and dielectric methods illustrated that barely 3% or less of the water enters discrete cavities (micropores that are comparable in size to the size of water molecules) in the first stage of sorption. Subsequent sorption proceeds in these micropores with the formation of clusters of water molecules. Derivatographic studies of potato, wheat, rye, and maize ~ t a r c h ”have ~ shown that only the potato starch lost water at temperatures between 30 and 150°C (19%). The other starches retained their humidity over this temperature range. Hysteresis loops for sorption-desorption are nearly 100% reproducible, but a consistent trend is observed: a decrease of the amount of adsorbed water with increasing numbers of sorption-desorption cycles. In the seventh subsequent run of the sorption-desorption cycle at 35”C, the volume of adsorbed water is by a factor of 1/30. This decrease suggests the possibility of a small amount of damage to the structure of either the starch matrix or granules, and even the amylose helix. Such a conclusion may also be drawn by observation of the thermolysis of air-dried, azeotropically ” dried (with benzene), and oven-dried (2 h, 130 “C) potato s t a r ~ h . ~Drying affects the structure of starch, but this effect is rather insignificantat elevated temperatures (see Table XV). Again it is qualitatively in agreement with the observations of Ulmann and S ~ h i e r b a u m ~ who ~ ~ - reported ~’~ the alteration of starch as dependent on the mode of drying. The irreproducibility of sorption-desorption hysteresis may be due to irreversible changes in the swelling of starch granules. Swelling obviously increases the surface area of s t a r ~ h . ~ ~ ’ . ~ ~ ’ Later studies by Poliszko et ~ 1 . documented ~ ~ ’ that, in freeze-dried starch gels, several complex conformational transitions take place that increase the rigidity of starch chains nearly 105 times. The free energy of mechanical relaxations due to the reorientation of hydroxymethyl groups reaches 38 kJ/mol; the activation energy due to the local conformational mobility of polymeric chain is reported at 48.7 kJ/mol.

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

302

XV TABLE Differential Thermal Analysis (DTA), Thermogravimetric Analysis (TGA), and Differential Thermogravimetric Analysis (DTG) of Potato Starch Dried by Three Methods (All Temperatures in 0C)3ss -

Air-dried starch DTA”: lOO(730) en; 258 (89) en; 269 (30) en; 277s en; 283 (<30) en; 300s ex TGAh: -19% (30-156); -34% (239-300) DTG‘: 96 (57.5); 256 (27.5); 282 (300); 344 (70) Oven-dried starch (130°C. 2 h) DTA“: 245 (30) en; 260s en; 280s en TGA”: -30% (236-280) DTG‘: 246 (20); 254s (60); 270 (165). Azeotropically dried starch (benzene) DTA“: 249 (40) en; 261s ex; 265 (30) en; 276s ex; 289 (<20) en TGA’: -30% (234-276) DTG‘: 249 (22.5); 253s (55);267 (125). Figures in parentheses represent the area (in mm2) under each normalized to the basis of 100.00 mg. Shoulders in the data are denoted by %” Endothermic and exothermic processes are denoted by “en” and “ex,” respectively. The range of temperature in “C, in which the mass indicated is lost. is given in parentheses. The peak height ( X 10.’ mg) is given in parentheses. The shoulders are denoted by “s.”

‘H NMR studies”’ of hydrated starch were performed with water concentrations from 6.3 to 15.7%, and the results indicate a sharp decrease of the line width as the water content increases. The interpretation of these data excludes the sole involvement of the primary adsorption sites of starch, and it suggests that a multilayer water structure is produced by condensation. This would explain the observation of four different states of water: water of surface adsorption, capillary-adsorption water, second outer-layer water, and constitutional water. In the case of the isotherm for potato starch saturated with water (that is, approximately 30% moisture content), pore structure investigations and thermodynamic properties363indicated that 10%of the initial moisture corresponds to approximately one molecule of water sorbed per glucose unit. The remaining portion of the water gives a ratio of two water molecules per glucose unit. Swelling of starch begins on sorption of the second water molecule. At water concentrations of approximately lo%, the water is highly mobile and reorients anisotropially.^^ At higher concentrations this orientation of water is retained and mobility is restricted.365According to Hoover and H a d ~ i j e vcapillary ,~~~ condensation does not occur below water concentrations of 34% in such a variety of starch. It should be emphasized that, below this moisture content, starch granules are effectively nonporous, and pores are generated by an excessive proportion (234%) of moisture.

COMPLEXES OF STARCH WITH INORGANIC GUESTS

303

The state of constitutional water seems to be best interpreted by spectroscopic studies with Hertzian f r e q ~ e n c y ~I3C ~ ~ CPMAS-NMR -~~' spectra3'l and primarily by X-ray diffraction studies. Different powder-diffraction patterns are exhibited by native and dried In addition, swelling does not change these patterns.373Further s t ~ d i e sprovided ~ ~ ~ . evidence ~ ~ ~ that anhydrous starch is amorphous (see also the series of papers by Rundle et 4.5.18.48.49.65.I Oh.I 10.11 1.1 23,I24,129)* revealed that the specific volume of starch unPycnometric dergoes a systematic variation that corresponds to the sorption hysteresis of water. In the region of 0-13% water, a large apparent compression was noted which accompanies swelling. The two subsequent steps in the regions of 13-30% water and over 30% water are assisted by a slight volume contraction and expansion, respectively. The heat of wetting of starch was determined"' as -130.98 J/g and was negatively dependent on the degree of crystallinity of the material. The hydration of starch augments its crystallinity, and the degree of crystallinity depends on the water content, at least in the region of 0.5 to 25% water. In addition, the degree of crystallinity increases37' upon application of high pressures of up to 1.2 X 10' Pa. There is clearly a discontinuous effect of water on starch crystallinity. Depending on the variety of starch, water concentrations of up to -9% result in the formation of hydrogen bonds which bridge hydroxylic groups of adjacent glucose units of the same chain. This causes the coiling of amylose. Additional water molecules form hydrogen bonds between more arbitrarily located hydroxy groups in the starch structure. At elevated temperatures, sorption is controlled mainly by the primary hydroxylic groups of starch.380Imberty et al.52 have shown that the distribution of the water of hydration in starch depends on the crystal structure of starch (see Fig. 1). In the A-crystal structure, hydrogen bonds couple 0 - 2 to 0-6 and 0 - 4 to 0 - 3 of the maltotriosyl units, whereas in the B-crystal structure these oxygen atoms belong to maltosyl units. Water maintains the 1.1-nm distances between the axes of the starch double helix. The heat of immersion of dry corn starch in water is -123.5 J/g and decreases to -113.4 J/g after its compression. The average hydrogen-bond energies of water-starch species vary381from -8.57 to -7.80 kcal/mol. Studies by Rundle et al., which were reviewed by Szejtli and A u g ~ s t a t , ~ ~ ~ point to the helical structure of amylose in aqueous solutions. The dimensions of the amylose helix are well recognized, and therefore the structural similarity of the turns of the helix to cyclomaltohexaose (a-cyclodextrin) is sound. The a-cyclodextrin-water complex contains two guest molecules of water inside the cavity.3x' Therefore, it may be accepted that part of the constitutional water of starch is included inside the amylose helix. Indeed,

304

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

water molecules are contained inside the left-handed, sixfold amylose chain. It is the Vh-amylose with an orthorhombic unit-cell in which the oxygen atom bound to C-6 is gauche to 0-5 and gauche to 0-4. They form an extensive network by hydrogen bonding.384It should, however, be emphasized that, although water in neutral solutions causes coiling of amylose, the coil structures are randomly arranged. The structure that can be strictly considered as helical requires intervention from another complexing agent and/or an alkaline solution.385 3. The Mechanism of Water Sorption

Sorption and desorption of water by starch exhibits hysteresis behavior. In maize starch, the sorption branch of the hysteresis loop corresponding to moisture contents above 16% displays exponential kinetics”‘:

U = Up exp (-Wt),

(3) where U is the mass of water (in g) adsorbed per gram of starch, Up is the equilibrium water concentration, k is constant, and t is time. The kinetics of this part of the sorption curve are affected by temperature, an effect that is attributed to temperature effects on hydrogen bonding between hydroxyl g r o ~ p s . ~ ”At- ~lower ~ ~ temperatures, the total volume of sorbate increases; simultaneously the hygroscopicity of starch increases.3y4As shown by Egorov and Sh~hegoleva,3’~ water sorption proceeds with three significant entropy changes (Fig. 31), which are independent of temperature. The entropy is, however, inversely dependent on the temperature. First, a significant increase of entropy occurs at -8% adsorbed humidity. Further increases in the concentration of adsorbed humidity produces two subsequent critical regions, which are separated by only a small decrease of entropy at about 18-19% humidity.

J1 mole:C16O

AS’

20°C

140 50°C

1

2

0

~

8

5 10 15 20

0

’

C

H20.%

FIG.31.-Entropy changes of starch on its moisturizing at 20,50, and 80°C. (By permission from Egorov and Sh~hegoleva.~”)

COMPLEXES OF STARCH WITH INORGANIC GUESTS

305

The rate of sorption and the absorptive capacity of starch has been ~ ’ ~ the equation analyzed by Sunner et ~ 1 . using log

x,= p + a&,

(4)

where X , is the mass fraction of adsorbed water at a time t, a is a parameter describing the rate of adsorption, /3 is the adsorptive capacity parameter, and Z , = log [r/(t + l)]. For maize starch, values for (Y and p are reported as 1.0661 and 1.870, respectively. Corresponding values for pregelatinized maize starch are 0.7830 and 3.0881, respectively. The role of temperature in the a and p parameters is not understood for these and other starch varieties. It is apparent, however, that the pregelatinization of starch increases its water-binding capacity with a simultaneous decrease of the rate of water uptake. It is also reported that vacuum-dried starch adsorbs moisture up to an equilibrium concentration at a rate of -1% per hour.”’ The kinetics of desorption of water from a maize starch is given by the equation””: U

=

Uo - a exp

- (Wt),

(5)

where a and k are constants, U, is the preliminary moisture concentration of the starch, and U is the final moisture content of that starch. At 0.5% relative atmospheric humidity there is a linear relationship between -log ( Uo - U ) and llt. However, increases in the atmospheric humidity cause this relationship to become increasingly nonlinear. This is an example of the lack of the sorption-desorption hysteresis. The reasons for the appearance and disappearance of the sorption-desorption hysteresis remain unclear. Urqhart3” rejected the effects of the surface tension of water and capillary condensation. He attempted to interpret the phenomenon on the basis of water molecules interacting with various sequences of available hydroxy groups in starch. Similar condensation was presented by Pier~e.~‘” Desiccation engages free hydroxyl groups, which mutually interact upon reaching a free state. On sorption, only those remaining free participate in sorption. Sorbed water tends to restore the original orientation of hydroxyl groups to the surface. However, in view of the results presented by other i n v e s t i g a t ~ r s , ” ~ ~this ~ ” explanation ~~~”~ is incomplete. Swelling of starch may also be involved, and occurs at room temperature. For two cornstarch systems, it was reported that the average energy of the hydrogen bonds between water and solid starch ranges from -35.9 to - 32.6 kJ/rn01.~”~ These values reflect differences in the state of the surface of the solid. The latter value reflects the contributions of two specific stages of water-vapor condensation: ( I ) decreased motions of water molecules as the result of a transition from three- to two-dimensional ordering during formation of a monolayer film, and (2) spreading of water molecules on

306

PIOTR TOMASIK A N D CHRISTOPHER H. SCHILLING

the surface of the solid starch and swelling. Water molecules are concluded to be rather loosely bound, based on measurements of relaxation times at high frequencies. The relaxation process is characterized by activation parameters AF = 25-33 kJ/mol, AH = 29-46 kJ/mol, and AS = 20-42 J / m ~ l . k . ~ " ' *Nevertheless, ~"~ the overall energy resulting from the sorption of water causes conformational transformations of ~tarch.4"~ Curves of the activation energy as a function of water content also show regions that indicate the form in which the water molecules exist.& According to various estimations, the monolayer of water constitutes 6-7.7% (based on dry mass at 40°C) of the moisture c ~ n t e n t . " " ~ . ~ ~ ~ Hellman et ~ 1 . ~attempted ~ ' to find a relationship between the swelling of various starches and the water content. They observed hysteresis behavior, as shown in Fig. 32. The authors could not find a general relationship between swelling and water content, an effect which they assumed is caused by intergranular porosity. Increases in the swelling rate were attributed to hydration at junction points of a three-dimensional molecular network. The results suggest opening of the molecular structure of starch beyond the volume of the water that entered the structure. Decreases in the rate of swelling were attributed to sorption in voids. A n equation for determining the specific volume (SV) of hydrated potato starch was rep~rted''~to be satisfactory for humidity concentrations ( x ) of up to 28.32%at 25°C: SV

=

0.65016 + 0.0010139~+ 0.00004926~~.

(6) This equation provides an excellent fit with the experimental data when the water content exceeds 15%.The effect of the temperature (T) on the equilibrium water content ( V ) for temperatures below 45°C is given by a linear equatiodY2: 60

50

s- 40 U

30 0

m

-z g

20 10

O 5 1 0 0 5 1 0 0 10 2 0 0 10 20 Increase over vacuum dry dameter , ' 1 0 FIG.32.-Swelling of corn (C), potato (P), tapioca (T) and waxy corn ( W ) starch as the function of the water content. (Reprinted with permission from N. N. Hellman, T. F. Boesh. and E. H. Melvin, J. Am. Chem. Soc., 74 (1952) 348-350. Copyright 1952 American Chemical Society.)

COMPLEXES OF STARCH WITH INORGANIC GUESTS

V

=

5.723 - 0.824 log T.

307

(7)

The range of validity of this equation can be extended by using the relationship shown in Fig. 33 between the relative humidity of the atmosphere and the water content in starch. A model for water diffusion in starch granules is also presented, which provides a good fit to experimental data, although it neglects ~ w e l l i n g : ~ " ~ - ~ ' " D

=

Doexp (ac).

(8)

In this equation, Do is the diffusion coefficient (which is dependent on the particle size distribution), and c and a are empirical constants. Additives to starch exert varying effects on the kinetics of water sorption. For example, lipids do not significantly affect the content of adsorbed water. The mode of starch defatting can also influence moisture sorption by molecules of the defatting solvent occupying active centers of sorptio11.3~~ The addition of either sucrose or lipids to starch has the same effect on both branches of the hysteresis curve.386*398 Some additives, such as dimethyl sulfoxide or ammonium rhodanide, induce selectivity of the adsorption and solvation of ~ t a r c h . ~Sulfur " dioxide accelerates water sorption regardless of the t e m p e r a t ~ r e . ~Pretreatment '~ of starch with sulfur dioxide usually increases the water ~orption.~" Studies on the sorption of components of water-alcohol mixtures are discussed in Section IV. 4. Significance of the Origin of Starch It is known that the origin of starch controls the amylose-to-amylopectin ratio, the granule size, and other properties. The role of the origin of starch on water sorption-desorption (Tables XIV and XV) and related

21

-

$ 20 0

I

16 12

8 L

0

10 20 30

40 50 60 70 80 90 100 Relative humidity,

FIG.33.-The adsorption isotherm of dry potato starch layers in the range of 20-90°C. (Reprinted from reference 409, pp. 611-622 by courtesy of Marcel Dekker, Inc.)

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

308

phenomena has been experimentally confirmed. X-ray diffraction analy,iS46.414 of cereal and tuber starches revealed that the crystal structure is identical in the dry state. Adsorbed moisture from the high-pressure treatment of potato starch with steam produces notable changes in the degree of crystallinity (Table XVI). However, water is also sorbed in amorphous region^!'^.^'^ It may be seen from this table that the degree of crystallinity of amylomaize starch and amylose is similar to, and slightly lower than, that of potato starch. In contrast, retrograded potato starch exhibits a much lower degree of crystallinity. Also, the thermodynamic functions for water sorption on amylose and amylopectin are the same (AF" 301 = -8.16 kJ/ = -43.5 kJ/mol, and AS"301 = -117 Jlmol K)!I6 However, the mol, adsorption of water by amylopectin is enhanced in comparison with amylose. The heats of adsorption for both of these compounds are estimated as -39 and -57.3 kJ/mol, re~pectively.~'~ The equilibrium sorption capacities of potato starch, amylose, and amylopectin at 20°C and 75.6% relative humidity are equal to 15.8, 14.2, and 16.7%, re~pectively.~'~ Sorptive capacity is one of the most important properties, and it has been investigated by many authors for several varieties of s t a r ~ h . ~ ~ ~ - ~ ~ ~ Sair and Fetzer,"*" and also R a k o ~ s k i ? compared ~ ~ - ~ ~ ~the water-retention capacities of wheat, arrowroot, and potato starch, and the results were similar. Among the following starch varieties, the sorptive capacity decreases in the order given: potato > arrowroot > wheat. The order potato > corn > wheat was reported by El-Khawas et d4*' Nara el reported the order potato > tapioca > waxy rice > sweet potato > rice; S m 0 1 i n a ~reported ~~ the orders potato > maize > rice > wheat at low humidity and potato > rice > maize > wheat at high humidity. These orders do not agree with the order reported in Table XVII on the effect of desiccation on the water retention of starch. Based on these data. the

TABLE XVI Degree of Crystallinity as a Function of the Variety of Starch and the Partial Pressure of Water Vapor, as Determined by X-Ray Diffra~tion~'~ Fraction Crystallized Partial Pressure

Potato

Amylomaize

Amylose

Retrograded Potato

0 0.20 0.40 0.60 0.80

0.21 0.20 0.22 0.22 0.27

0.20 0.17 0.19 0.19 0.20

0.19 0.19 0.19 0.20 0.19

0.06 0.06 0.10 0.11 0.12

COMPLEXES OF STARCH WITH INORGANIC GUESTS

309

TABLE XVII Effect of Desiccation at Room Temperature on the Water Adsorption-Desorption Behavior of Starch420

Loss in Water Retention Capacity, mg HZWg of Dry Starch Starch

Desorption

Adsorption

Arrowroot

15.2 11.1 28.2 8.2 19.6 3.9

5.3 8.2 9.1

Corn Potato Rice Sago Wheat

4.0 8.6 4.4

Difference 9.9 2.9 19.1 9.9 11.0 +0.5

authors4’” classified starch into three groups: cereal starch (wheat, corn, and rice), pit or root starch (sago, arrowroot, and sweet potato), and tuber starch (potato). Furthermore, taking into account the theory of the involvement of hydroxyl groups in water binding and sorption, they deduced that potato starch has more hydroxyl groups available (that is, it is less intramolecularly associated). There is a suggestion423that, at low moisture concentrations, intragranular diffusion controls the sorption process, whereas at high moisture concentrations, the dissipation of heat due to the heat of sorption is the controlling factor. There is also a report that the values of the adsorption capacity of water vapor on various swelling starches are practically independent of the origin of the s t a r ~ h . 4Other ~ ~ attempts at interpreting the differences in sorption capacity by starch of different varieties failed; the authors correctly observed that surface condensation is not the only mode of ~orption.4’~ The hydration of starch evokes thermal effects which are obviously also dependent on the starch variety. This is true because the external temperature does not affect426the macrostructure and microstructure of starch below 140°C. An estimation of the heat of sorption is useful in determining the concentration of bound ~ a t e r . The ~ ~heat ~ -of~adsorption ~ ~ ranges from 0.255 to 0.100 kJ/mol and depends not only on the variety of starch, but also on the mode of drying of starch prior to measurement (Table XVIII).426 The effect of the mode of drying can be used to study the role of water in changing the chemistry and structure of the starch matrix. For example, a series of papers on dehydration of starch had particular emphasis on drying by infrared r a d i a t i ~ n .In~ this ~ ~ situation, . ~ ~ ~ drying can cause dehydration of terminal glucose groups and dextrinization. Bursting of starch granules always takes place (125°C for maize starch and 158°C for barley starch),

310

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING TABLEXVIII Effect of the Method of Drying of Starch on the Heat of Remoi~turization~~ (Wlmol)

Starch

Oven Drying

Vacuum Drying

Corn Potato Rice Wheat

0.225 0.255 0.150 0.113

0.025 0.100 0.234 0.134

and this fact helps to maximize the water uptake by exposing more surface area."3h The rate and extent of granule swelling is also an interesting factor. The swelling power depends on the variety of starch and is not well understood. Figure 34 presents the results of swelling studies of a few thick-boiled ~tarches.4~~

5. Analysis of the Water Content This problem, which is important from both theoretical and practical standpoints, has been solved in many ways. Some approaches have been limited to the estimation of the overall water content, a problem interesting mainly for practicians. Gravimetric methods seem to be the least sophisticated because the final result is available from the difference of the mass of sample before and after drying (usually for 2 h at 130°C). It is possible

50

60 70 80 90 Extraction tempemture,'C

FIG.34.-Swelling patterns of various thick-boiling starches (P, potato; T, tapioca; W, waxy corn; C, corn; S, sorghum). (From Elder and Schoch!")

COMPLEXES OF STARCH WITH INORGANIC GUESTS

311

to distinguish between the equilibrium water concentration and the total concentration of sorbed water by using a simple vacuum-drying procedure!0'.43x-"0 Eberius"' reported a convenient and precise method of estimating the water content by Karl Fischer titration. Dumanskii and Yakovkina442 proposed the measurement of starch humidity by selective adsorption of water from 15-25% aqueous solutions of sucrose. A more sophisticated technique involves measurements of the dieIectric properties of starch, which is compressed in an apparatus presentedM3in Fig. 35. Using this approach, dielectric properties are measured at low frequencies (316 Hz-10 kHz), and attenuation of electromagnetic waves is measured at a high frequency (9.3 GHz). A key result is that the electromagneticwave damping is linearly dependent on the starch humidity at a given applied pressure (Fig. 36). A group of Japanese workers369evaluated the dielectric properties of starch, and hence the water content, using audio frequency measurements. Infrared and Hertzian frequencies have also been used for this purpose.368*370 Freeman4" compared the results of bound water measurements by calorimetric, cryoscopic, and dilatometric methods. The results were comparable and slightly higher than those measured by the refractometric method of D u m a n ~ k i iFrom . ~ ~ ~heat-capacity data, the amount of starch in suspension may also be determined. Among various methods, the tensimetric method delivers the greatest amount of practical and theoretical information. This method has been reviewed in detail and refined by Schier(see also ref. 445 for a later modification). The infrared method

FIG.35.-Apparatus for measuring the effect of humidityon the damping of electromagnetic waves. 1, screw press; 2, measurementcell; 3, electrode; 4, bow dynanometer;5, starch sample. (Reprinted with permission from M. Boruch, S. Brzezinski, and A. Palka, Acta Aliment. Pol., 1 1 (1985) 115-124.)

312

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

736 kPa 521 kPa

265 kPa A,dB

15

17

19

21

23 25 27 Humidity, O/O

29

FIG.36.-Changes in electromagnetic wave damping, A, as a function of starch humidity at various pressures. Three potato-starchvarieties are denoted by three different point patterns. (Reprinted with permission from M. Boruch, S. Brzezinski, and A. Palka, Acra Aliment. Pol., 11 (1985) 115-124.)

was also presented by the same author jointly with Ulmann.446N e m i t ~ ~ ~ ~ presented a hygroscope for the determination of water content, and Nara et introduced a method involving centrifugal filtration. Among other methods, thermogravimetric analysis has also been d es ~ri b ed .~’ IV. STARCH COMPLEXES WITH OTHER NONMETALLIC GUESTS

1. Introduction BET (Braunnauer-Emmett-Taller) sorption isotherms of starch indiate^^^,‘"'^ that only very small volumes of nitrogen is achieved quickly (within 10 min). Sorption-desorption proceeded without hysteresis; however, complete degassing of starch was not possible by heating to 105°C at nitrogen partial pressures as low as torr. Air is also adsorbed in small amounts.48 Convincing evidence for the sorption of various gases on starch . ~observed ~ ~ similar amounts was presented as early as 1928 by K ~ d aHe of contraction of an isolated frog heart after exposure to starch samples that had been previously exposed to different gases, including COz, CO, coal gas, NO, N 2 0 , HzS, S02, C12, HZ,02,ethene, ethyne, and methyl chloride. The author concluded that inorganic gases are better sorbed than organic gases, and that a critical factor is the polarity and not the size of the gas molecule. As compared to charcoal and bolus, starch has rather poor sorptive affinity.

COMPLEXES OF STARCH WITH INORGANIC GUESTS

313

cr-cyclodextrin forms inclusion complexes with C 0 2ranging in their sorp1O:l to 1:l. Moreover, the inclusion of C 0 2inside the cavity tion from45".451 is the sole mechanism of adsorption involved in such cases. Therefore, it is not a good model system for the starch-C02 complex because other adsorption mechanisms are typically present in starch, for instance, capillary sorption and surface sorption. However, starch has a low (-W3 wt %) capacity to sorb C02, and the sorption is rever~ible.4~~ In addition, carbon dioxide cannot replace water from its starch c0rnplex.4~~ Sulfur dioxide and ammonia are adsorbed by starch in at an approximate amount of one molecule per glucose unitf' however, the structure of these complexes has not been investigated. As with iodine, starch forms an inclusion complex with bromine vapor.'"' Depending on the starch variety, different colors are developed by the complex. Maize and wheat produce an ochre color, rice produces a lightbuff color, potato and sago develop a pale-yellow color, and cassava forms a cream color.69 Iodine cyanide (and bromine)-amylose complexes are brown-black and dark brown, respectivelyFM The adsorption of chlorine and iodine proceeds according to the Freundlich isotherm. A discontinuity on the Freundlich isotherm plot is reported, which possibly results from the swelling of starch granules.454 Sorption of various gases (02, N2, C 0 2 ,and He) on wheat flour, soybean flour, potato starch, and wheat starch has been investigated in order to study the effect of those gases on the functional properties of processed food products. Results indicate that such properties improved only after flour and starch were treated with ~ h l o r i n e . ~The ~ ' *adsorptivity ~~~ of various gases by starch has been ree~amined.~" Liquid ammonia quickly forms a gelatinous paste with Tomasik et ~ 1attempted . ~ to~prepare ~ inclusion complexes of starch with colloidal sulfur. A key result was that inclusion inside the starch matrix was only possible in small amounts because of the large relative size of the sulfur micelles. It has been discovered that starch adsorbs onto graphite, a phenomenon that is employed in processing sulfide ores containing graphite.46" The adsorption of starch on quartz and hematite has been studied in more In this case, adsorption is related to the balance between electrostatic interactions and hydrogen bonding. Interparticle bridging is also observed as a result of the adsorption of starch molecules at the interface (flocculation). 2. Complexes with Arrhenius Acids and Bases

a. Complexes with Acids.-According to Rakowski,"62 starch adsorbs insignificant amounts of acid; however, other authors do not support this opinion. For example, Lloyd463reported that the sorption of hydrochloric

314

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

acid is weaker than the sorption of salts and hydroxides. He observed that the sorption of hydrochloric acid follows the sorption rule for acid concentrations below 0.4 M. Adsorption affinities vary among starches of different origins, as presented in Fig. 37. Hydrogen chloride gas is readily adsorbed by starch at concentrations of up to slightly more than one gas molecule per glucose unit. The resulting complex is black and water-soluble, indicating that hydrolysis accompanies adsorption.454Gaseous hydrogen chloride does not exhibit a strong ability to penetrate the inside of starch granules unless moisture is absent. Granules containing 3-4% moisture are readily penetrated by hydrogen chloride and undergo dextrinization."@The sorption of hydrogen chloride by starch sol causes its peptization, perhaps because of the discharge of the b. Complexes with Metal Hydroxides.-Interactions of alkali-metal hydroxides with starch have been studied in order to recognize unique aspects of the base-catalyzed degradation of starch. For example, R a k o ~ s k i ~ ~ ' . ~ ~ ~ recognized that the sorption of those hydroxides plays a key role in the degradation, which proceeds as a two-step process. The first step entails surface sorption and is followed by the hydroxide penetrating into the interior of grains as a second step. Since adsorption equations did not fit the experimental data very precisely, it is possible that something more

0.02

0.06

0.10

0.14

0.18

HCI absorbed,

FIG.37.-Adsorption of hydrochloride by starch of various origins (M, maize; R, rice; A, arrowroot; P, potato; C, cassava). [Reprinted with permission from Lloydjh3Copyright (191 1 ) American Chemical Society.]

COMPLEXES OF STARCH WITH INORGANIC GUESTS

315

than adsorption occurs in such cases. The equation which fits the experimental data best is c2 =

P + CUP,

(9)

where c2 is the concentration of a compound sorbed per gram of starch (in mequiv), c1 is the concentration of adsorbed compound at the point of equilibrium, and p and p are empirical constants. The P and p constants are respectively dependent and independent of several hydroxides: NH40H, LiOH, NaOH, KOH, Sr(OH)2, and Ba(OH)2. Among these hydroxides, ammonium hydroxide is only slightly sorbed. Later, R a k o w ~ k ide~~~,~~~ duced that the combination of alkali hydroxides with starch leads to the formation of “alkali starchates” according to a reversible reaction: St-H

+ Metal-OH

P St-Metal

+ H20.

Reychler independently presented a similar sugge~tion.~’ The following complexes with sodium hydroxide and starch have also been characterized in solution: (2C6Hl0OS* NaOH), (C6Hl0OS NaOH), and (ChHl0O5 2NaOH),,470.471 Lipatov reported studies of alkali diffusion in He discovered that the adsorption velocity from dilute solutions is higher than that from concentrated solutions and obeyed the empirical relation

-

k

=

(l/t) In [m/ (rn - y Q ) ] ,

-

(10)

where t is the time, m is the mass of adsorbate, y is a constant, and k is proportional to the diffusion constant and to the surface area of starch. In addition, k is inversely proportional to the thickness of the diffusion layer. As mentioned before, the mode of adsorption of calcium, stontium, and barium hydroxides differs from that of alkali-metal hydroxides. This difference is attributed to a lower adsorption velocity of metal hydroxides of the second nontransition group. Moreover, the quantitative results of adsorption, are different, as ~ h o ~in Table n ~ XIX. ~ ~ . ~ ~ ~ As discussed next, barium salts form insoluble complexes with starch. Similar behavior is exhibited by the complex of Ca(OH)2 with starch. This property is utilized for the precipitation of starch from aqueous solution, a process that is rather s10w.47s.476In his subsequent paper, Rako~ski~ studied ~ ’ the effect of salts on the adsorption of metal hydroxides; it was observed that increases in salt increased the adsorption of hydroxides. This effect is absent in the case of the adsorption of NH40H. More extensive demonstrated the following order of adsorption capacities: Ca(OH)2 = Ba(OH)2 > KOH > NaOH > LiOH > Me3(PhCH2) ~ ~ * ~ ~and ~ Leach et aL478accordingly NOH > Me4NOH. R a k o ~ s k i , 4Lloyd,”63

316

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

TABLE XIX Adsorption of Alkali-Metal Hydroxides by Different Varieties of Starch&’ Starch Arrowroot: Bermuda St. Vincent Potato

Wheat Rice

Alkali

Wt% Absorbed

NaOH NaOH NH40H LiOH NaOH WOW2 Sr(OH)2 Ba(W2 NaOH NaOH

43.3-36.1 44-35 4.2-1 41.1-35.5 45.8-38.6 19-76 17.2-75.8 78-73 47.6-36.9 42.8-43.9

stated that there are negligible differences in the hydroxide-adsorption behavior of different starch varieties. It was o b ~ e r v e d that ~ ~ ’starch ~ ~ ~retards ~ precipitation of AI(OH)3 formed from aluminates. This effect is caused by chemisorption and formation of a colloidal suspension, and is useful in organic synthesis, as in MeenveinPondorff-Verley redox reactions with aluminum alcoholates. Adsorption of cupric hydroxide from ammonium hydroxide by starch causes the sorption of CU(NH&(OH)~.The sorption of this copper species is more effective than the sorption of Ba(OH)2; however, the process is complex and cannot be expressed by a simple formula.48’On the other hand, fractionation of potato starch by means of A1(OH)3 has been reported.4E2The complex of CU(OH)~, ammonium hydroxide, and starch has been patented as a germicide and algicide composition.483

3. Complexes With Salts a. Introduction.-Native starch always contains a variety of metal cations which are held by phosphoric acid residues of the amylophosphoric portions of starch. These cations thus exist as cations of salts and not as a part of any inclusion complex. Several authors observed that the mechanical properties of starch gels (namely, their strength and elasticity) greatly depend on water hardness (see, for instance, refs. 484 and 485). Such changes can be attributed to the formation of complexes with salts. Intervention of the ion exchange in the phosphoric acid moieties is quite sufficient to cause this observed e f f e ~ t . ~ ~ ~ , ~ ~ ’ The formation of starch complexes with metal salts of metal oxides is of practical interest in, for instance, textile finishing (see discussion by Hal-

COMPLEXES OF STARCH WITH INORGANIC GUESTS

317

ler4"). As shown by Dykyj,"89metal cations influence the sorption of dyes on potato starch according to the acidity or basicity of a particular dye. In the case of basic dyes, cations sorbed on starch decrease the sorptive capacity in the order Ba2+> Sr2+>> Ca2+>> Cs+> Rb+ > NH4+> K+> Na+ > H+. Aluminum salts after hydrolysis produce a basic starch which is therefore capable of sorbing acidic dyes. Several authors observed the effects of salts (cations and anions) on the swelling and gelation of starch. It is accepted that peptization of starch by salts and metal hydroxides results from a disturbance of the hydration of The precipitation of starch is caused by the formation of sorption, capillary, and inclusion c o m p l e x e ~ . ~The ~ . ~formation ~ - ~ ~ ~ of complexes between starch and salts is supported by several experimental facts. For instance, the addition of CaC12to starch changes its optical rotation, which is further changed by the addition of stannic chloride. Such behavior is not uniform with respect to all salts tested and indicates the selectivity of starch in complexation with The addition of 0.3% KBr, 0.05% MnS04,or 0.05% C0S04 causes changes in the UV absorption spectra of starch. It should be emphasized that these changes become more pronounced after storage,"9xwhich in turn suggests that this process is not simple surface sorption. In her papers, Jane499*5"indicated that these effects are due to breaking of the water structure, that is, due to changing of the conditions of hydration and electrostatic interactions of ions with starch (complexation). Figure 38 illustrates the effects of selected cations on starch swelling and gelation. Rey~hler~'"-~''~ distributed selected salts into three groups according to their effect on starch at room temperature. It was observed that NaCl, CaC12,and MgS04 do not cause any swelling, whereas all of the

t

54'0 52.0

,

, \sr,

1

2

, 3

4

\

5

Ion Conc., N

FIG.38.-Effect of cations on the swelling and gelatinization of starch. (From S e i d e ~ n a n n . ~ ~ )

318

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

following cause typical swelling: KI, ZnC12,Na[HgC13], NH4N03,AgN03, Pb(C103)2, NaC104, KSCN, and NH4SCN. In contrast, NH4C1, SnCI2, HgCI2,Pb(N03)2,Ba(SCN)*,and sodium benzoate cause atypical swelling. The swelling rate is only slightly dependent on the chemistry of the salts.504 It was o b ~ e r v e by d ~'H~ NMR ~ ~ ~that ~ swelling of starch grains causes ordering of water molecules. In the case of wheat starch, the buildup of such a well-organized matrix is reached. It increases the electrolytic conduction of ions, perhaps because the ions are hydrated to a lesser extent.507 On the other hand, cations affect 'H NMR spectra mainly by the magnitude of splitting, and the effect of ions of the I1 nontransition groups is more pronounced than that of the ions of the I nontransition Figure 39 illustrates the effects of some anions on those processes. For example, anions that are poorly hydrated are adsorbed more strongly on the surfaces of starch micelles. The salts that are adsorbed in a polar manner bring water with them, since they are strongly hydrophilic and thereby 80 76 72 0

66 Frn 6L

60 56 52

40 44

40

36 32

20

24 20

FIG. 39.--Influence Seidemann."m)

06 0.8 1.2 16 2 0 24 28 3.2 36 4.0 4 4 48 Salt ,mole of some salts on swelling and gelatinization of starch. (From

COMPLEXES OF STARCH WITH INORGANIC GUESTS

319

increase the hydrophilic properties of the micelle. In turn, this influences swelling."'9 Starch readily adsorbs anions containing a polar sulfur atom, such as a thiocarbonyl group (also organic compounds bearing such groups). Thus, the adsorption becomes polar, and swelling takes place.509According to Jane,s"" the NCS- anion complexes with starch in a manner similar to that of the 13- anion. Perhaps because of complexation, starch inhibits the hemolytic action of cyanide anions on erythrocytes510and prevents the formation of humus from them.'l' The behavior of complexes of sodium salicylate is another trivial example of the role of anions in starch complexes. The phenolie group is acidic and can cause some hydrolysis of ~ t a r c h . ~ ' Usually, ~ * ' ~ ~ C1- and S042- retard swelling, but this effect also depends on the accompanying cation."' The type of anion also controls the possible mode of complex formation. The interior of amylose and some branches of amylopectin can assume a helical structure, the interior of which is hydrophobic. Thus, under favorable structural circumstances, inclusion complexes can be formed that hold salt anions inside the helix, so that the accompanying cation is excluded and becomes activated through lack of direct contact with the charge field of the anions. Such phenomena are observed in the case of salt-inclusion complexes of cycl~dextrins.~'~ However, studies on the effect of lithium chloride, bromide, and rhodanide, and also MgS04 on the specific rotation of starch suggest that there is an interaction of ions with C-2 and C'-3 OH groups of glucose units."6 Such complexes can readily be formed with long-chain carboxylates salts, sulfates, and so 0n.s17-520 Studies by Fischer and S ~ h w a i b o l d ~as~well l as by Seidemann491show that there are significant differences between starch varieties in response to their being treated with salts. A general method for synthesizing starch-metal complexes with Ba, Ca, wherein Sr, Be, Mg, Zn, Al, Fe, and Cu is given by a 1926 British alkali starches were treated with one or more metal salts. The cupric complex was reported to have disinfecting properties. Sorptive properties of starch in thin-layer chromatography with respect to such metal ions as Fe, Hg, Sn, As, Sb, and Cr have been presented in several paper^.^^^-"^ In the twentieth century, several papers were published on the degradation of starch by salts, especially those which cause hydrolysis (see, for instance, papers by B i e d e ~ - m a n n ~and ~ ' *Haehn529). ~~~ This observation was frequently criticized as an artifact and was finally abandoned.530Nevertheless, the changes of starch-sodium salicylate complexes previously menshow ' tioned,S12.513 as well as the known hydrolysis of starch by a l ~ r n , 5 ~ that the question cannot be generalized. Moreover, in 1964 a paper was

320

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

publisheds3’ on the hydrolysis of starch gels by chlorides (Table XX). The authors assumed that the salts undergo hydrolysis in aqueous solution, generating hydronium ions. The hydrolytic activity correlates with the radius of the salt cation, and the rate of hydrolysis varies significantly with the type of salt added. The water-binding capacity of starch is affected by salts in the following order for cations: K > Mg > A1 and K > Na > Li. Similarly, the waterbinding capacity is affected by anions in the following order: CNS > I > Br > NO3> Cl > SO4.The effect of cations is stronger than that of anions.s33 The addition of various salts to potato starch on its compression up to 1.2 X lo9 Pa had only a small effect on the thermal properties of starch, as measured by thermogravimetry/differential thermogravimetry/differential thermal analysis (TGIDTGIDTA). Only FeC13, CoC12, and I2 caused significant effects.62 The viscosity of starch gels is also affected by salts. For example, potassium salts decrease their viscosity, but manganese (MnS04) and cobaltous (CoCI2)salts increase the viscosity at concentrations as low as 0.1 M.s34As described by Merckel, the viscosity of gels (from starch sols) blended with salts increases as a function of the third power of the lyotropic number at a given concentration. The lyotropic series CNO > I > Br 2 1 0 3 > F > Br03> C1, which is also obeyed in the case of the sorption of sodium salts in liquid ammonia,4s8displays a concave relationship with respect to the viscosity, as shown in Fig. 40. Similar relations have also been found for potassium salts.s3sIn some cases, a linear relationship is observed between the gel viscosity and lyotropic numbers assigned to anions and ~ a t i o n s . ~ ~ ~ - ~ ~ The gelation characteristics of starch blended with salts also depend on the variety of starch; in addition, the time- and temperature-dependent rheological behavior (amylogram) varies in a more complex manner with the lyotropic numbers.s39 More extensive studiess4” have revealed that SO4’-, PO:-, S 2 0 3 ’ - , and NaF increase the temperature of gelation; NaCl.

TABLE XX Hvdrolvsis of Starch in the Presence of Some Metal Chloridess3*

Metal Ion A13+ Fe3+

cu2+ Ni2+ Mn2‘ Cd”

Goldschmidt Radius, A

pH

Period for Total Hydrolysis, Days

0.51 0.67 0.72 0.78 0.91 1.03

0.9 0.4 1.o 4.2 0.9 3.7

2 8 to 90 140

t

COMPLEXES OF STARCH WITH INORGANIC GUESTS

321

1.160 1

4

4

5

6

7

8

9

5

6

7

8

9 10 11

10 11 12 13 14 N

12 13 14

N FIG.40.-Relationships between the lyotropic number, N,and the viscosity of starch gels. (From MerckeLs")

NaBr, and NaI decrease that temperature; and CO2- and HC03- have no effect. Studies of the effects of electrolytes on the strength of starch gels were performed by S h i m i ~ u . It ~ ~should ' be mentioned that homogenous gels could not always be achieved. Neither wheat nor corn starch forms542 gels with ZnCI2,NH4CI, and (NH4)2S04. The effects of the electrolyte concentration on gel viscosity are typically insignificant. For example, it was reported543that a 100-fold increase of the electrolyte concentration changes the viscosity by only 23%. Such a result suggests that, again, only interactions of ions with a phosphoric acid moiety are involved. However, the effect of salts on the specific rotation of starch gels points to interactions between ions, and the amylose helix and amylopectin.516 Thermal effects of electrolyte adsorption on potato starch have also been observed.476For the alkali-metal salts, adsorption and accompanying swelling are reversible. Coacervation and flocculation of starch gels provide other evidence of starch-metal ion interactions. Coacervation can be achieved, for example, by blending starch gels with various salts, including NaC1, KC1, Na2C03, NaHC03, Na2S04, and CaC12,s""~s4s Flocculation of starch sols has been reported546with MgS04, sodium halides, acetates, sulfates, and isocyan a t e ~ . The * ~ ~state of hydration of starch seems to be the most critical factor. It was also observed that the rate of coagulation by three salts increases in the order KCl < CdC12< AlCl,; activation energies for these salts are, respectively, 1.9 X lo3, 25.1 X lo3, and 107.75 X lo3 kcal/m01~~~ and are related to the electrolyte concentration.

322

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

Rendelman published549a detailed review on starch-metal-ion complexes in 1978. b. Complexes with Nontransition Metal and Ammonium Salts.Relatively little attention has been paid to the combination of starch with ammonium salts. Starch has been reported to accelerate the decomposition of ammonium nitrate.ss0 S ~ h o c h showed ~~l that ammonium nitrate decreases the gelation temperature of starch to as low as room temperature. Ammonium sulfate increases the gelation temperature; with a 30% admixture of ammonium sulfate, starch does not gelatinize on boiling. The effect of ammonium carbonate on the viscosity of a starch gel is negligible.552 Ammonium chloride and sulfate do not form homogenous gels with some varieties of However, complexes of starch with ammonium chloride have been patented as hardening agents for amine resinsss3 and also to prevent the formation of brown spots during the ironing of clothes.”* Sorption of NaCl onto starch was recognized qualitatively by Dem o ~ s s yand ~ ~quantitatively ~ by Lloyd.463Maize starch exhibited better sorption than arrowroot starch, but the author noted that the adsorption rate is not a function of the surface area available for sorption. Because the process is fast ( 5 min) at room temperature, there is evidence of normal surface adsorption. The adsorption of NaCl has a so-called negative character in contrast to many other salts which exhibit positive adsorption?s5 The adsorption of NaCl increases the sorptivity of various organic dyes on This property is utilized in the textile printing of cellulose fibers that have been impregnated with starch. Because of negative sorption, acidic dyes are readily sorbed onto The use of calcium chloride and ammonium rhodanide also demonstrated good sorption behavior.5s8 It was reported that the electrolysis of 2-5% aqueous solution of starch containing sodium chloride or sodium sulfate yields a composition which is used for household cleanser applications.559Heating of an aqueous starch suspension in the presence of sodium sulfate at pH 6 increases the gelation temperature and vis~osity.”~~~’ Ironing starch can be prepared from starch and NaHF2.s62Gels of high viscosity are available from starch with sodium dihydrogenphosphate and disodium hydrogen-pho~phate.~~~ The presence of sodium phosphate in starch stiffens gels and stabilizes the v i s c o ~ i t y . ~ ~ Also, magnesium and calcium ions readily adsorb onto starch. In the case of magnesium, equilibrium is reached more slowly than in the case of calcium (see Fig. 41)s6sand the equilibrium saturation concentration is lower. Starch adsorbs approximately 86 mg of calcium per gram of starch independently of pH; equilibrium is reached within 20 min. The binding capacity of starch is not decreased by g e l a t i n i z a t i ~ n . ’ ~In~ .an ~ ~alkaline medium, CaC12forms a defined compound with starch that is free of chloride

COMPLEXES OF STARCH WITH INORGANIC GUESTS

323

OD060

- 0.0050 ‘0,

I *0.0040 0.0030

O.OOZSL, 0.0021

.

,

124 8

,

,

24

48 Tirne,h

FIG.41.-Adsorption of calcium and magnesium ions by starch as a function of time. The solid line represents adsorption of magnesium ions and the pointed line represents adsorption of calcium ions. P, potato starch; W, wheat starch; M, maize starch. (From Hollo et

anions.567A difference has been noted565in the salt-binding capacity of different starch varieties. For example, potato starch adsorbs almost twice as much as wheat and maize starch. The authors demonstrated that defatted maize starch exhibits the same binding capacity as potato starch. Another group of authors566demonstrated that the binding ability of cassava starch is higher than that of maize and waxy maize starch. Separation of amylose and amylopectin was attempted, based on the selective sorption of various cations.56xRussian workerP9 separated arnylose from amylopectin on calcium phosphate columns at pH 5.7. Amylose could be eluted with phosphate buffer, whereas amylopectin could not. The complexation of starch by calcium salts is readily observed polarimetrica11y570.571 and by conductivity meas~rements.~’~ The interaction of starch with CaC12 lowers the conductivity by a larger amount than with NaCI. Complexation of soluble starch with CaC12 progressively changes the specific rotation of starch from the initial [aylDZ0 = +196.68 to 196.80, 199.01, 200.80, and 201.60 at CaClz concentrations of 3.75,7.50,15.00, and 30.00%, respectively. The [aID2” value decreases in aqueous CaCI2 solutions, as shown in Table XXI. All of these results contradict former statements concerning the amount of calcium which is bound to starch5&if it is assumed that only one, uniform type of interaction exists between starch and calcium ions. Variations in the specific rotation coefficient of starch were observed at calcium concentrations in excess of the equilibrium calcium concentration. This effect is attributed to calcium ions clathrated in the gel net. The adsorption of starch on kaolinite does not exceed 4%, whereas on bentonite nearly 23% of maize starch is adsorbed. It has been proved by infrared spectroscopy that hydrogen bonds are involved without any ion e~change.~” The formation of a calcium complex also increases the digestibility of

324

PlOTR TOMASIK AND CHRISTOPHER H. SCHILLING

TABLE XXI Temperature Effects on the Specific Rotation of Aqueous Starch Solutions571 Specific Rotation, [a]D, Degrees Temperature, 'C

30% CaCI2 Added

Hz0

Difference

80 70 65 60 55 50 45 40 35 30 25 20 15 10

194.53 196.00 196.51 196.54 197.06 197.54 197.55 197.59 198.06 199.65 201.oo 201.05 201.24 201.50

182.01 183.57 184.05 185.01 186.52 188.03 189.50 190.00 192.01 194.91 196.93 196.68 196.85 197.34

12.52 12.43 12.46 11.53 10.54 9.51 8.05 7.59 6.05 4.74 4.07 4.37 4.39 4.16

~tarch.~" Calcium chloride forms complexes with starch after it is pretreated with sodium silicate and alum; this product is used to produce pigment for rubber, paint, paper, and ~eramics.5~~ Complexes of starch with CaC12have been patented as drilling and described as dispersing media.576A complex of starch with calcium formate and sodium nitrite preserves silage and makes it difficult to ferment.577Blending glycerol and an aqueous solution of CaC12with potato starch gives a product used for printing rolls.57' The formation of a barium-starch complex is well k n ~ w n ~ ~ Stern"' ~-~"; determined its composition as (C6Hlo05)8Ba0.Complexation of starch with barium is also used to precipitate starch from its solution. The complex of starch with borax has interesting physical properties. The interaction between borax and starch is purely physi~al.~'~ The formation of this complex is described by a first-order equation with an activation energy of -16 kcal/moL5@' As shown by Leach et ul.,478starch sorbs the sodium metaborate (Na2B02)component of borax and rejects the H3B03component. It was reported that a colloidal solution of such a complex exhibits good ~ p i n n a b i l i t yThe . ~ ~ ~addition of this colloidal solution to paper was also reported to increase the wet strength, the degree of sizing, and its fire resistance.586The use of such a complex was also described as a container material for pesticide encapsulation587and for the sedimentation of alumi*~" preparation of a typical comnum ore residue^.^" M ~ r a k a m i ~ ' ~reported

COMPLEXES OF STARCH WITH INORGANIC GUESTS

325

plex: 3 mmol borax per gram of starch were heated at 90°C for 1 h. Calcium borate can be used instead5” in order to decrease the water solubility. A titanium oxide additive is also reported to improve the functional properties of the comp~sition.~’~ Several other modifications of starch-borax complexes are reported. For example, a starch-CaC12 (>35%) complex precipitated with borax gives a product that is dispersible in water and exhibits good adhesive proper tie^.^'^ A complex of starch with borax acidified with H2S04is also soluble in cold water.594Good adhesive properties may also be achieved by complexation of starch with borax in sodium hydroxide s o l ~ t i o n .A~ combination ~ ~ * ~ ~ ~ of starch with sodium tripolyphosphate and borax has been used as a treatment for textiles which is stable on ironing.597 A similar composition, without polyphosphate, is also patented598for use as a liquid laundry starch that is stable in freezing environments. Complexes of boric acid in borated starch have been d i s c ~ s s e d . 5 ~ ~ Starch is sorbed on alumina, more strongly on neutral alumina than on acidic alumina. The amylose and amylopectin components are sorbed with different degrees of effectiveness. Amylose can be eluted by an acidic buffer and amylopectin by a neutral buffer.600It is possible to fractionate starch components using a gel-separation column that is filleld with acidic and basic A1203 in the upper and lower parts of the column, respectively. Amylose adsorbs on basic alumina and amylopectin on acidic The complexation of sodium aluminate by starch accelerates decomposition of the ~ a l t , ’ ’ ~perhaps * ~ ~ ~ ~by hydrolysis of the salt and uptake of sodium hydroxide by starch. Starch complexed with sodium aluminate is used to agglomerate starch sludge when the complex has a low concentration of starch; it acts as a colloid when the complex contains a high concentration of starch.604Complexes simultaneously containing sodium aluminate (or A1203),borax, and trisodium phosphate are used in paper manufacturing to provide a high,filler percentage and mechanical strength.605Other alkalimetal aluminates complexed with starch have also been patented for this purpose.606Starch-aluminate complex solutions have a moderate effect on modulus stability (shape retention) in contact with solid phasesm7 An aluminum nitrate-starch complex has been patented for coating paper.608 A complex of starch (100 parts), aluminum formate (16.3 parts of 22% aqueous solution), and paraffin (16.3 parts) in water (62.2 parts) has been reported as a fabric-treating composition.609Complexes of cooking starch with alum are also used as thickeners for printing dyes, finishing compositions, and sizes.610An intramolecular complex of starch with AlCb was prepared by treating starch with AlC13 to yield a product containing AlC12 and AlCl (cross-linking) moieties. This complex is water-soluble but stable to hydrolysis (although not to hydration) and thermal treatment.611

326

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

A complex of starch with talc has been used for coating rubber granules."' Complexes of starch with SnC12 and Na2Sn03 are used as coatings, adhesives, and additives for drilling muds. They have exceptionally high viscosity and are stable on aging.613y6'4Starch complexes with lead are unknown, but complexation is utilized in dehydration and flocculation of lead slimes,h's protecting lead and lead alloys from corrosion in soft and also in chemical and environmental analysi~.~''A complex with As( 111) chloride (dichloroarsenous starchate) has been prepared.611Phosphorus( V) halides are reported618to form a 1:l complex with amylose having a stability constant of 1.5 X 10' at 25°C. c. Complexes with Salts of Transition Metals.-Starch forms two types of complex with CuS04: Positive and negative complexes are formed with diluted and concentrated solutions of CuS04, respectively.'" Sorption of silver(I) halides"' on starch (and on other hydrophilic polymers) influences the grain size of those halide^.^'' Complexation of starch with ZnC12results in insolubilization6" and resistance to microbial molding.564Complexation of starch with zinc fluorosilicate is patented for the ironing of clothes.562 Some varieties of starch form nonhomogenous gels with ZnC12.'40 Iodine zinc chloride causes layer swelling of starch granules, a phenomenon which may have some applications in the analysis of starch variety and chemistry.621Complexation with HgI preserves starch solutions.622An ammonium iodomercurate complex with starch is used to determine nitrogen concentrations in ~ t e e 1 . hComplexes ~~ which form between starch and organic titanium( IV) compounds of the general formula (Ti(OH),(OOCR)4.x (where R represents 1 to 4 carbon atom alkyl groups) have been reported and are perhaps responsible for stiffening of starch solutions.624Starch hydrated with titanium( IV) oxide or titanyl sulfate (5-10%) has been used in production of cardboard and p l y ~ o o dTitanium( . ~ ~ ~ IV) chloride reacts readily with starch, causing the evolution of hydrogen chloride. The resulting residue is readily hydrolyzed by water, causing precipitation of Ti02. The starch is also dextrinized, and its aqueous solutions have a low Coatings and adhesives result from the complexation of starch with titanates, zirconium( IV) chloride, or zirconium oxynitrate [ZrO(N03)2].6'4 Starch-iron complexes are reported as biologically active sources of iron.627,628 In one report, it is warned that such complexes may produce sarcomas as a result of long-term exposure.629investigation^^^' have shown that, independently of the ferric salt used, the maximum capacity of the salt in starch is 2-7 mg%. Because pH 5.8 is more conducive to stability than low pH values (3 or lower), higher concentrations of ferric salt are not advisable. Shi D e ~ h e n g recommended ~~l blending starch (100 g) with trisodium citrate (25g) and 2 M FeC13 (500 mL) in water (2500 mL) at

COMPLEXES OF STARCH WITH INORGANIC GUESTS

321

pH 7.5-8.5, adjusted with 20% aq. NaOH. In this case, the resulting iron was present in the form of FeO(0H). L e s z c z y n ~ ksaturated i~~~ potato starch with either FeC13 or ferric citrate, both at concentrations of 3.33 X lo-’, and 3.33 X 3.33 X M. The product is degradable by alpha amylase. These procedures are safe because FeC13 does not hydrolyze starch unless hydrogen peroxide is added; in this case the rate of hydrolysis increases with time.633Another procedure uses Fe(OH)3 (100 mg) in a colloidal state. It is stabilized by starch (10-50 parts) and made neutral by dilute ammonium hydroxide. It was not possible to precipitate a stable complex using CaCl’ or ethanolY4 it was noted that the presence of Ca’+ ions in the reaction mixture strongly inhibited the adsorption of ferric oxides from solution.635 S ~ n o w i e c kused i ~ ~ ~colloidal ferric oxide (136 mL), starch (6 g in 66 mL of water), and sodium hydroxide (0.7 g) in this procedure. After maintaining this reaction mixture for 1 h at 60°C, the complex was precipitated with alcohol. Studies by K r a ~ s e ~revealed ~ ’ , ~ ~that ~ only “meta ferric hydroxide” coagulates with starch, and amylose was not active in either case. It has also been reported that iron is released from starch-ferric complexes upon contact with ascorbic On working with mixtures of starch and ferric salts, redox reactions between components should be taken into account.531 The addition of potassium ferrocyanide to a starch solution increases the viscosity and the strength of the gel.@’ The Co(I1) ion is adsorbed on amylopectin in a manner similar to the Fe(II1) It is well known that starch-iron complexes are suitable for fortifying bread and flour with iron. The state of iron in flour, dough, and bread was investigated by Leichter and J ~ s l y n . @Iron ~ salts influence the whiteness of sweet-potato starch, but this effect is variable.614It was also reportedH5 that colloidal iron interacts with starch, a process which is used to fractionate starch into three portions: The first portion (80% of the total amount) is formed by colloidal iron itself, the second (9% of the total) is formed by iron and electrolytes, and the third portion (11%of the total) is not precipitated at all. Complexes of starch with salts of metals of the group VIII transition elements (particularly palladium complexes) are highly efficient regio- and stereoselective catalysts for the hydrogenation of plant 0ils.646*H7 Cerium( IV) salts are used to initiate graft polymerization of starch. In order to graft-copolymerize starch, a complex of Ce( IV) was prepared by blending cornstarch with Ce(NH4)z(N03)6-HN03reagent in the ratio of 75 glucose residues per Ce( IV) c ~ m p o n e n t . ~ ~ ~ @ ’ ACKNOWLEDGMENT The authors wish to thank the Office of Basic Energy Sciences at the U S . Department of Energy for supporting this research.

328

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

REFERENCES (1) H. Suzuki and N. Taguchi, Kenkyu Hokoku-Asahi Garasu Kogyo Gijutsu Shoreikai, 36 (1980) 311-321; Chem. Abstr., 94 (1984) 209108b. (2) V . I. Nazarov, Poverkhnost. Khim. Soedin. i Rol v Yavleniyakh Adsorbtsii, Sbornik Trudov Konf: Adsorbtsii, (1957) 268-270. (3) M. Baczkowicz, P. Tomasik, and S. Wiejak, Staerke, 38 (1986) 338-341. (4) R. E. Rundle, J. Am. Chem. Soc., 69 (1947) 1769-1772. (5) R. S. Stein and R. E. Rundle, J. Chem. Phys., 16 (1948) 195-207. (6) K. C. Sen. Chem. News, 129 (1924) 194-196. (7) R. Haller, Kolloid-Z., 41 (1927) 81-87. (8) G. Barger, Some Applications of Organic Chemistry to Biology and Medicine,McGrawHill, New York, 1930, 127-176. (9) C. T. Greenwood, Adv. Carbohydr. Chem., 11 (1956) 335-396. (10) P. Pascal, Nouveau Traite de Chemie Minerale, Masson and Cie. Editors, Paris, 1960, VOI. XVI, 476-477. (11) V. 0.Mokhnach and N. M. Rusakova, Dokl. Akad. Nauk SSSR, 135 (1960) 1143-1146. (12) F. Watanabe, Kensa To Gijufsu, 2(5) (1974) 28-31; Chem. Abstr.. 84 (1976) 147038111, (13) W. Saenger, Nafurwissenschafien,71 (1984) 31-36. (14) W. Banks and C. T. Greenwood, Starch and Its Components, Edinburgh University Press, Edinburgh, 1975. (15) J. Hollo and J. Szejtli, in J. A. Radley (Ed.), Starch and Its Derivatives. 4th edn.. Chapman and Hill, London, 1968, Ch. 7. (16) J. J. Colin and H. Gauthier de Claubry, Ann Chim., Ser. 1, 90 (1814) 87-100. (17) F. Stromeyer, Ann. Phys., 49 (1815) 146-153. (18) R. E. Rundle, J. F. Foster, and R. R. Baldwin,./. Am. Chem. Soc., 66 (1944) 2116-2120. (19) W. A. Jacquelain, Ann. Chim. Phys., Nouv. Ser., 73 (1840) 167-207. (20) F. W. Kuester, Liebigs. Ann. Chem., (1894) 360-379. (21) W. Harrison, Proc. Chem. SOC., 26 (1910) 252-253. (22) W. Harrison, J. SOC. Chem. Ind. (London),29 (1910) 1335. (23) W. Harrison, Z. Chem. h d . Kolloide, 9 (1911) 5-9. (24) G. Barger and E. Field, J. Chem. SOC., 101 (1912) 1394-1409. (25) R. Berczeller, Biochem. Z., 133 (1922) 502-508. (26) M. Bergmann, Ber., 57B (1924) 753-755. (27) A. K. R. Choudhury, Sci. Cult. (India), 13 (1947) 40-41. (28) R. Haller, Kolloid-Z., 41 (1927) 81-87. (29) E. Angulescu and J. Mirescu, J. Chim. Phys., 25 (1928) 327-342. (30) N. C. Turner, Science, 108 (1948) 302. (31) A. Roncato, Arch. Ital. Biol., 74 (1924) 146-149. (32) L. W. Andrews and H. M. Goettsch, J. Am. Chem. SOC., 24 (1902) 865-881. (33) E. Angulescu and J. Mirescu, Bul. Soc. Romaine Stiinf., 27 (1924) 59-64; Chem. Abstr., 20 (1926) 686. (34) R. Berczeller, Biochem. Z., 84 (1917) 106-117. (35) A. Burgstaller, Chem. Ztg., 36 (1912) 589. (36) T. Onami, Kagakrc to Kyoiku, 38 (1990) 578-579; Chem. Abstr., 114 (1991) 163132f. (37) L. A. Nikolaev and G. N. Fadeev, Dokl. Akad., Nauk SSSR, 276 (1984) 638-642. (38) M. Katayama, Z. Anorg. Chem., 56 (1907) 209-217. (39) H. Euler and S. Bergmann, Kolloid-Z., 31 (1922) 81-89. (40) G. Barger and F. J. Eaton, J. Chem. Soc., 125 (1924) 2407-2414. (41) J. B. Firth and F. S. Watson, J. Soc. Chem. Ind. (London),42 (1923) 308T-310T.

COMPLEXES O F STARCH WITH INORGANIC GUESTS

329

(42) (43) (44) (45) (46) (47) (48) (49) (50) (51)

A. Lottermoser, Z . Angew. Chem., 34 (1921) 427-428. A. Lottermoser, Z . Elektruchem, 27 (1921) 496-501. J. Dykyj, Chem. Listy, 38 (1944) 227-231. R. Haller, Helv. Chim. Actu, 28 (1945) 450-455. S. Bear, J. Am. Chem. Soc., 64 (1942) 1388-1392. W. J. Katzbeck and R. W. Kerr, J. Am. Chem. SOC., 72 (1950) 3208-3211. R. E. Rundle and D. French, J. Am. Chem. Soc., 65 (1943) 1707-1710. R. E. Rundle and F. C. Edwards, J. Am. Chem. Soc., 65 (1943) 2200-2203. A. Vogel, Nuchricht. Rep. Phurm. (1874) 7. A. Imberty, H. Chanzy, S. PCrez. A. Buleon, and Vinh Tran, J. Mol. Biol., 201

(52) (53) (54) (55) (56) (57) (58) (59) (60) (61) (62) (63) (64) (65) (66) (67) (68) (69) (70) (71) (72) (73)

A. Imberty, A. Buleon, Vinh Tran, and S . PCrez, Staerke, 43 (1991) 375-384. W. Hallgren, Svensk Farm. Tids., 27 (1923) 357-365. R. Schering, Brit. Patent 501,246 (1939); Chem. Absrr., 33 (1939) 6001. W. L. Minto, U.S. Patent 2,540 486 (1951); Chem. Absrr., 45 (1951) 5721. M. K. Pal and P. K. Pal, Mukromol. Chem., 190 (1989) 2929-2938. L. Vanino and A. Schinner, Arch. Phurm., 253 (1915) 47-51. K. H. Meyer and P. Bernfeld. Helv. Chim.Actu, 24 (1941) 389-393. J. J. Chinoy, F. W. Edwards, and H. R. Nanji, Analyst, 59 (1934) 673-680. A. Boutriac and S. Fabry, Bull. Soc. Chim.B i d , 24 (1942) 108-116. T. Handa and H. Yajima, Biopolymers, 79 (1980) 723-740. E. Kudla and P. Tomasik, Stuerke, 44 (1990) 253-260. M. Samec, Kolloid. Beih., 47 (1937) 91-99. J. M. Bailey and W. J . Whelan, J. B i d . Chem., 236 (1961) 969-973. F. L. Bates, D. French, and R. E. Rundle, J. Am. Chem. SOC., 65 (1943) 142-148. M. Samec, Kolloid. Beih., (1925) 55-77. L. Cotton, L. H. Lampitt, and C. H. Fuller, J . Sci. Food Agric., 6 (1955) 656-660. M. Richter, Staerke, 22 (1970) 167-174. J. Huebner and K. Venkataraman, J. Soc. Dyers Colorists, 42 (1926) 327-332. J. Szejtli, Period. Polytech., Chem., 7 (1963) 259-288. J. Field 2nd and L. G. M. Baas-Becking, J. Gen. Physiol., 9 (1926) 445-450. A. T. Phillips and V. R. Williams, J. Food Sci., 26 (1961) 573-577. A. L. Potter, V. Silveira, R. M. McCready, and H. S. Owens, J. Am. Chem. Soc., 75

(74) (75) (76) (77) (78) (79) (80)

D. M. W. Anderson and C. T. Greenwood, J. Chem. Soc., (1955) 3016-3023. J. A. Thoma and D. French, J. Am. Chem. Soc., 82 (1960) 4144-4147. L. E. Simerl and B. L. Browning, Ind. Eng. Chem., Anal. Ed., 11 (1939) 125-128. M. Samec, Ber., 73A, (1940) 85-92. M. Samec, E. Waldschmidt-Leitz, and K. Mayer, Z. Physiol. Chem., 242 (1936) 165-168. S. Lansky, M. Kooi, and T. J. Schoh, J. Am. Chem. Soc., 71 (1949) 4066-4075. S. Ono, T. Watanabe, K. Ogawa, and N. Okazaki, Bull. Soc. Chem. Jpn., 38 (1965)

(1988) 365-378.

(1953) 1395-1398.

(81) (82) (83) (84)

643-648. Q. J. Peng and A. S. Perlin, Curbohydr. Res., 160 (1987) 57-72. W. T. Smith and G . T. Smith, Curbohydr. Res., 10 (1969) 598-600. J . Mazurkiewicz and P. Tomasik, J. Phys. Org. Chem., 3 (1990) 493-502.

J . Mazurkiewicz, M. Nowotny-Rozanska, and P. Tomasik, Chem. Scriptu. 28 (1988)

375-379. (85) A. W. Lorenz, Chem. Analyst, 19 (1916) 20-21. (86) N. R. Dhar, J. Phys. Chem., 28 (1924) 125-130. (87) D. A. Godina and G . P. Faerman, Zhurn. Obshch. Khim., 20 (1950) 966-978.

330

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

I. M. Kolthoff, Pharm. Weekblad, 56 (1919) 391-393. J. W. Ellms and S. J. Hauser, J. Ind. Eng. Chem., 6 (1914), 553-554. R. Reilhes, C. R. SOC.Biol., 135 (1941) 554-557. T. Kuge and S. Ono, Bull. Chem. SOC.Jpn., 33 (1960) 1269-1272. S. Ono, S. Tsuchikashi, and T. Kuge, J. Am. Chem. SOC.,75 (1953) 3601-3602. Y. Miyazaki, Saga Daigaku Nogaku Zho, 11 (1960) 83-86; Chem. Absrr., 55 (1961) 20469b. (94) L. Ernst, Biochem. Z., 232, (1931), 346-351. (95) A. Payen and J. Persoz, Ann. Chim. Phys., Nouv. Ser., 56 (1834) 337-371. (96) S. Naegeli, Beitraege zur naheren Kenntniss der Staerkegruppe, Leipzig, 1874. p. 49. (97) A. Clementi, Arch. Farm. Sper., 20 (1915) 256-268. (98) P. Marquardt, Klin. Wochschr., 18 (1939) 1396-1397. (99) K. Takahashi and Y. Tori, Yakugaku Zmshi, 89 (1969) 538-543; Chem. Absrr., 71 (1969) 33381u. (100) C. Lange, Biochem. Z., 95 (1919) 46-84. (101) I. Markevich, Kolloid. Zh., 5 (1939) 63-67. (102) R. Sutra, Bull. Sac. Chim. Fr., (1947) 737-738. (103) H. D. Murray, J. Chem. Soc., 127 (1925) 1288-1294. (104) H. Euler and K. Myerbaeck, Ark. Kem. Mineral. Geolog., 8 (9) (1921) 1-29. (105) S. Mukherjee and S. Bhattacharyya, J. Indian Chem. SOC.,23 (1946), 121-132. (106) R. R. Baldwin, R. S. Bear, and R. E. Rund1e.J. Am. Chem. SOC.,66 (1944) 111-115. (107) K. Freundenburg, E. Schaaf, G. Dumpert, and T. Ploetz, Naturwissenschaften, 27 (1939) 850-853. (108) C. S. Hanes, New Phytol., 36 (1937) 101-141, 189-239. (109) J. A. Thoma and D. French, J. Phys. Chem., 65 (1961) 1825-1828. (110) R. E. Rundle and R. R. Baldwin, J. Am. Chem. SOC., 65 (1943) 554-558. (111) R. E. Rundle and D. French, J. Am. Chem. SOC.,65 (1943) 558-561. (112) J. Hollo and J. Szejtli, Period. Polyrech., 2 (1958) 25-37. (113) A. Cesario and D. A. Brant, Biopolymers, 16 (1977) 983-1006. (114) J. M. Bailey, W. J. Whelan, and S. Peat, J. Chem. SOC.,(1950) 3692-3695. (115) E. Waldschmidt-Leitz and M. Reichel, Z. Physiol. Chem., (1934) 76-80. (116) Y. Nakamura, T. Shimomura, and J. Hirano, J. SOC. Agric. Hokkaido Univ., 50 (1957) 141-157. (117) F. Cramer, and W. Herbst, Naturwissenschaften, 39 (1952) 256. (118) W. Dwonch, H. J. Yerian, and R. L. Whistler, J. Am. Chem. Soc., 72 (1950) 1748-1750. (119) J. Hollo and J. Szejtli, Brauwissenschaft, 13 (1960) 380-386. (120) T. D. Simpson, Biopolymers, 9 (1970) 1039-1047. (121) J. Tanaka, Kagaku Kyoiku, 28 (1980) 257-63; Chem. Absrr., 93 (1980) 237894~. (122) D. L. Mould, Biochem. J., 58 (1954) 593-600. 66 (1944) 2116-2120. (123) R. E. Rundle, J. F. Foster, and R. R. Ba1dwin.J. Am. Chem. SOC., (124) R. E. Rundle, J. Chem. Phys., 15 (1947) 80. (125) F. Cramer, Angew. Chem., 64 (1952) 437-447. (126) M. Kertesz and F. Vonderviszt, J. Am. Chem. Soc., 104 (1982) 5889-5893. (127) H. Kim, Biopolymers, 21 (1982) 2083-2096. 102 (1980) 3215-3217. (128) R. C. Teitelbaum. S. L. Ruby, and T. J. Marks,J. Am. Chem. SOC., (129) R. J. Hach and R. E. Rundle, J. Am. Chem. SOC.,73 (1951) 4321-4324. (130) H. Murakami, J. Chem. Phys., 22 (1954) 367-374. (131) T. Handd, H. Yajima, and T. Kajiura, Biopolymers, 19 (1980) 1723-1741. (132) M. Noltenmeyer and W. Saenger, J. Am. Chem. SOC.,102 (1980) 2710-2722. (133) M. Noltenmeyer and W. Saenger, Nature, 259 (1976) 629-632. (88) (89) (90) (91) (92) (93)

COMPLEXES OF STARCH WITH INORGANIC GUESTS

331

(134) T. L. Bluhm and P. Zugenmeier, Carbohydr. Res., (1981) 1-10. (135) M. Schlamowitz, J. Biol. Chem., 190 (1951) 519-527. (136) B. Pfannemueller and G. Ziegast, Staerke, 35 (1983) 7-11. (137) F. Cramer, Chem. Ber., 84 (1951) 855-859. (138) F. Cramer, Red. Trav. Chim. Pays-Bas, 75 (1956) 891-901. (139) H. Rossotti, J. Polymer Sci., (1959) 557-558. (140) R. C. Schulz, R. Wolf, and H. Mayerhoefer, Kolloid-Z., Z. Polym., 227 (1968) 65-72. (141) J. F. Foster and B. Zucker, J. Phys. Chem., 56 (1952) 170-177. (142) Yu-Chang Hsieh and Kwang Hsien Hsu, Pei Ching Ta Hsueh Hsueh Pao-Tzu Jan K’o Hsueh, 4 (1958) 478-489; Chem. Abstr., 53 (1959) 13772. (143) D. J. Manners and V. R. Wright, Biochem. J., 75 (1960) lop-11P. (144) J. F. Foster and R. L. Smith, Iowa State College J. Sci., 27 (1953) 467-477. (145) M. A. Swanson, J. Biol. Chem., 172 (1948) 825-837. (146) A. R. Archibald, I. D. Fleming, A. M. Liddle, D. J. Manners, G. A. Mercer, and A. Wright, J. Chem. SOC.,(1961) 1183-1190. (147) F. F. Mikus, R. M. Hixon, and R. E. Rundle, J. Am. Chem. SOC.,68 (1946) 1115-1123. (148) R. S. Higginbotham, Shirley Inst. Mem., 23 (1949) 171-184. (149) G. A. Gilbert and J. V. R. Mariott, Trans. Faraday SOC.,44 (1948) 84-93. (150) R. L. Whistler and G. E. Hilbert, J. Am. Chem. SOC.,67 (1945) 1161-1165. (151) T. Kobayashi and A. Yoshida, Bull. Agric. Chem. SOC.Jpn., 24 (1960) 538-540 Chem. Abstr., 55 (1961) 2757. (152) G. Ziegast and B. Pfannemuller, Int. J. Biol. Macromol., 4 (1982) 419-424. (153) H. Euler and Myrback, Ann., (1922) 1-24. (154) A. Lottermoser, Oesterr. Chem. Ztg., 27 (1924) 13. (155) A. Lottermoser, Z. Angew. Chem., 37 (1924) 84-85. (156) M. Tovbin and M. Feldman, Zh. Fiz. Khim., 13 (1939) 818-825. (157) J. Hollo and J. Szejtli, Przem. Spoz., (1957) 429-433. (158) J. Hollo and J. Szejtli, Period. Polytech., 1 (1957) 223-228. (159) J. Hollo and J. Szejtli, Fette. Seifen. Anschtrichmirtel, 59 (1957) 94-98. (160) J. Hollo and J. Szejtli, Brauwissenschaff, 13 (1960) 348-352. (161) A. Boutriac and S. Anglade-Thevenet, Bull. SOC. Chim. Fr., 9 (1942) 438-439. (162) R. A. Dimmick and C. Corley, Proc. Indiana Acad. Sci., 60 (1950) 141-144. (163) U. K. S. Gupta, A. K. Mucherjee, and K. K. S. Gupta, Kolloid-Z., Z . Polymer, 208 (1966) 32-34. (164) Y. Miyazaki, Saga Daigaku Nogaku Iho, (1960) 87-95; Chem. Abstr. 55 (1961) 4833. (165) S. Peat, W. J. Whelan,P.N. Hobson,andG. J.Th0mas.J. Chem. Soc., (1954)4440-4445. (166) J. Hollo, E. Laszlo, J. Szejtli, and A. Mandi, Staerke, I2 (1960) 351-358. (167) S . Gupta, A. K. Mukherjee, and K. K. Sengupta, Kolloid-Z., 208 (1966) 32-34. (168) Y. Miyazaki, Saga Daigaku Noguku Iho, 16 (1963) 67-75; Chem. Abstr., 62 (1965) 10654. (169) R. S. Higginbotham. J. Textile In~t.,40 (1949) T783-T794. (170) J. Szejtli, Staerke, (1966) 274-280. (171) G. L. Hatch, Anal. Chem., 54 (1982) 2002-2004. (172) B. L. Larson, K. A. Gilles, and R. Jennes, Anal. Chem., 25 (1953) 802-804. (173) M. Ito and S. Yoshida, Bull. Agric. Chern. SOC. Jpn., 23 (1959) 34-39. (174) T. Kobayashi and S. Yoshida, Denpun Kogyo Gakkaishi, 8 (1960) 48-55; Chem. Abstr., 57 (1962) 11439. (175) H. Suzuki, Denpun Kogyo Gakkaishi, 10 (1963) 107-1 10; Chem. Abstr., 63 (1965) 5881. (176) S. Nara, I. Maeda, and N. Kitabara, Bull. Agric. Chem. SOC.Jpn., 38 (1964) 509-513; Chem. Abstr., 63 (1965) 12221. (177) M. Ito and S. Yoshida, Bull. Agric. Chem. SOC.Jpn. 23 (1953) 34-39.

332

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

(178) D. Brunner and C. Leutner, Monutsh., 88 (1957) 1024-1030. (179) V. I. Deulin and V. I. Nazarov, Zh. Anal. Khim., 18 (1963) 1016-1020. (180) L. H. Lampitt and C. H. F. Fuller, Stuerke, 7 (1955) 223-226. (181) D. French and A. 0. Pulley, Stuerke, 15 (1963) 349-354. (182) E. J. Wilson, T. J. Schoh, and C. S. Hudson,J. Am. Chem. SOC., 65 (1943) 1380-1383. (183) C. T. Greenwood and S. McKenzie, Stuerke, 15 (1963) 444-448. (184) T. Kuge and S. Ono, Bull. Chem. SOC.Jpn., 33 (1960) 1273-1278. (185) W. Banks, C. T. Greenwood, and K. M. Khan, Curbohydr. Res., 17 (1971) 25-33. (186) J. Hollo and J. Szejtli, Stuerke, 8 (1956) 123-126. (187) J. Szejtli, M. Richter, and S. Augustat, Biopolymers, 5 (1967) 27-41. (188) W. Schneider, C. L. Cronan, and S. K. Podder, J. Chem. Phys., 72 (1968) 4563-4568. (189) K. Takahashi and S. Ono, J. Biochern., 72 (1972) 104-1043. (190) C. L. Cronan and F. W. Schneider, J. Phys. Chem., 73 (1969) 3990-4004. (191) M. Yamamoto, T. Sano, and T. Yasunaga, Bull. Chem. SOC.Jpn., 55 (1982) 1886-1889. (192) J. Eliassaf and M. Levin, Nature, 201 (1964) 1023-1024. (193) I. I. Alekseeva, A. P. Rysev, N. K. Ignateva, and A. I. Yakshinskii, Zh. Neorg. Khim., 16 (1971) 1654-1658. (194) A. Cesaro, E. Jerian, and S. Saule, Biopolymers, 19 (1980) 1491-1506. (195) G. K. Adkins and C. T. Greenwood, Curbohydr. Res., 3 (1966) 152-156. (196) J. Hollo and J. Szejtli, Stuerke, 9 (1956) 109-112. (197) W. L. Peticolas, Nature, 197 (1963) 898-899. (198) J. Hollo, J. Szejtli, E. Laszlo, G. S. Gantner, and M. Toth, Stuerke, 12 (1960) 351-358. (199) S. Hizukuri, Mem. Znst. Sci. Res. Osaka Univ., 15 (1958) 215-228; Chem. Abstr., 53 (1959) 3748. (200) A. T. Czaja, Stuerke, 17 (1965) 211-218. (201) R. W. Kerr, F. C. Cleveland, and W. J. KatzbeckJ Am. Chem. SOC.,73 (1951) 3916-3921. (202) J. F. Foster and E. E. Paschall, J. Am. Chem. SOC.,74 (1952) 2105-2106. (203) J. F. Foster and E. J. Pascall, J. Am. Chem. SOC.,75 (1953) 1181-1183. (204) L. H. Lampitt, C. H. F. Fuller, and N. Goldenberg,J. SOC.Chern. Ind., 60 (1941) 99-111. (205) C. D. West, J. Chem. Phys., 15 (1947) 689. (206) C. T. Greenwood and H. Rossotti. J. Polym. Sci., 27 (1958) 481-488. (207) H. Murakami, J. Chem. Phys., 23 (1955) 1979. (208) M. Tasumi, Chem. Lett., (1972) 75-78. (209) R. Bersohn and I. Isenberg, J. Chem. Phys., 35 (1961) 1640-1643. (210) G. Moyano Olson and R. A. Berg, J. Chem. Phys., 48 (1968) 1426-1427. (211) I. Isenberg and R. Bersohn, J. Chem. Phys., 48 (1968) 1427. (212) Y. Hoshino, Electrochem. SOC.Jpn., 18 (1950) 6-9. (213) B. Pfannemiiller, H. Meyerhoeffer, and R. C. Schulz, Biopolymers, 10 (1971) 243-261. (214) Joan-Nan Liang, C. J. Knauss, and R. R. Myers, Rheol. Actu, 13 (1974) 740-744. (215) C. F. Schoenbein, J. Prukt. Chem., 84 (1861) 385-409. (216) J. J. Pohl, J. Prukt. Chem., 83 (1861) 35-41. (217) R. Fresenius, Ann. Chem. Phurm., 102 (1857) 184-189. (218) A. Payen, C. R. Acud. Sci., 61 (1865) 1021-1023. (219) J. Personne, C. R. Acud. Sci., 61 (1865) 993-995. (220) C. Gauthier, and T. Nogier, C. R. SOC. Biol., 69 (1910) 156-157. (221) H. Bordier, C. R. Acud. Sci., 163 (1916) 205-206. (222) E. Rousseau, C. R. SOC. Biol., 93 (1925) 1482-1483. (223) H. Bordier, C. R. Acud. Sci., 163 (1916) 291-293. (224) L. Francesconi and R. Bruna, Guzz. Chim. ItuL, 64 (1934) 485-497. (225) M. K. Pal and A. Roy, Mukrornol. Chem., Rapid Commun., 6 (1985), 749-754.

COMPLEXES O F STARCH WITH INORGANIC GUESTS

333

(226) I. H. Halban and H. Eisner, Helv. Chim. Acfu, 19 (1936) 915-927. (227) T. De Leo, M. R. De Marco, and F. Badolato, Ricerca Sci., 27 (1957) 1812-1825. (228) L. Jonas, Ann. Pharm., 20 (1836) 40-50. (229) V. Griessmayer, Ann., 160 (1871) 40-56. (230) C. Meinecke, Chem. Zfg., 18 (1894) 157-160. (231) J. Pinnow, Z. Anal. Chem., 41 (1902) 485-488. (232) G. Rivat, Chem. Zfg., 34 (1910) 1141. (233) E. Chretien and H. Vanderberghe, Ann. Chim. Anal. Chim. Appl., 13 (1921) 19-23. (234) L. Deibner, Anal. Chem., 33 (1951) 207-215. (235) P. Arthur, T. E. Moore, and J. L. Lambert, J. Am. Chem. Soc., 71 (1949) 3260. (236) J. L. Lambert, Anal. Chem., 23 (1951) 1247-1250. (237) J. L. Lambert, Anal. Chem., 23 (1951) 1251-1255. (238) J. Hoelzl and E. Bancher, Osfer. Bof. Z., 111 (1964) 69-77. (239) V. Novak and V. Dlask, CON. Czech. Chem. Commun., 30 (1965) 908-912. (240) A. Beszterda and B. Jadzyn, Rocz. Akad. Roln. Poznan, 90 (1976) 3-7. (241) U. Kolodynska, Pr. Cenfr. Inst. Ochr. Pr., 37 (134) (1987) 127-135. (242) V. P. Ignatev and I. V. Kolomeitseva, Radiokhimiyu, 32(5) (1990) 114-117. (243) J. Hernandez Mendez, A. Alonso Mateos, M. J. Almendral Parra, and C. Garcia de Maria, Anal. Chim.Acru, 184 (1986) 243-250. (244) L. V. Melnikova, Zuvod. Lab., 56 (9) (1990) 26-27. (245) L. H. Lampitt, C. H. F. Fuller, and N. Goldenberg,J. SOC.Chem. Ind., 66 (1947) 142-147. (246) L. Paloheimo, Muuful. Aikuk., 20 (1948) 109-113. (247) S. Winkler and G. Luckow, Sfuerke, 17 (1965) 331-333. (248) T. Minoru, Kugawa Duiguku Nogakubu Gukuzuyubu Hokoku, 13 (1962) 180-184; Chem. Absrr., 59 (1963) 6711. (249) G. H. Cater and A. M. Nembert, J. Agric. Food Chem., 2 (1954) 1070-1072. (250) L. Szechenyi, Elelmezesi Ipur, 8 (1954) 96-97. (251) M. Richter, Nuhrung, 8 (1964) 106-107. (252) J. Charles, Bull. Soc. Chim. Biol., 36 (1954) 705-710. (253) N. Ivanov and R. Schultz, Bull. Inst. Textile, Fr., 42 (1953) 29-41. (254) L. M. Liggett and H. Diehl, AnaChem. News. 6 (1946) 9-10. (255) R. M. McCready, J. Guggolz, V. Silviera, and M. S . Owens, Anal. Chem., 22 (1950) 11561158. (256) Y. Otani and S. Takahashi, Hukko Kuguku Zasshi, 36 (1958) 448-452; Chem. Absrr., 53 (1959) 17415. (257) H. Kurasawa, T. Hayakawa, I. Igaue, Y. Kanauchi, and M. Kudo, NiigufaNorin Kenkyu, 19 (1967) 149-156; Chem. Absrr., 68 (1968) 483542. (258) H. N. De, N. H. Mian, and M. Haque, J. Sci. Ind. Res., 9 (1966) 243-246. (259) S. Singh. N. Nath, and H. P. Nath, Biochem. J., 63 (1956) 718-720. (260) C. T. Greenwood and J. S. H. Robertson, J. Chem. Soc., (1954) 3769-3778. (261) Yun-Hao Liao, Bull. Assoc. Agric. Chem. Nafl. Taiwan Univ., 10 (1961) 38-41; Chem. Absrr., 56 (1962) 2623. (262) G. L. C. Ciottoli Sollazzo. Tec. Moliforiu, 17 (1966) 57-60. (263) J. Hollo and J. Szejtli, Kolloid. Zh., 20 (1958) 229-232. (264) L. H. Lampitt. C. M. Fuller, and N. Goldenberg, J. Chem. SOC.Ind., 67 (1948) 97-101. (265) D. L. Mould and R. L. M. Synge, Biochem. J., 58 (1954) 585-593. (266) J. V. Halick and K. K. Keneaster, Cereal Chem., 33 (1956) 315-319. (267) H. Goerlitz and E. Wilberg, Z. Landwirfsch. Forsch. Unfersuh. Wes., 7 (1961) 392-398. (268) N. K. Matheson and J. M. Wheatley, Austr. J. Biol. Sci., 15 (1962) 445-458. (269) C. T. Greenwood and J. Thompson, Biochem. J., 82 (1962) 156-164.

334

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

(270) Z. Nikuni, Z. Hizukuri, Z. Tamura, and M. Sakai, Mern. Inst. Sci. Ind. Res. Osaka Univ., 19 (1962) 97-104. (271) D. G. Medcalf and K. A. Gilles, Cereal Chem., 42 (1965) 546-557. (272) E. Tolmasquim and F. R. T. Rosenthal, An. Acad. Brasil. Cienc., 33 (1961) 309-320. (273) F. Kurasawa, 1. Igaue, and T. Hayakawa, Nippon Nogei Kagaku Kaishi, 37 (1963) 16-20 Chem. Abstr., 62 (1965) 9338. (274) J. Eliassaf and J. B. Ayche, Sraerke, 17 (1965) 589-590. (275) T. M. Gorelkina, Byul. Prikl. Botan. Genet. Ser. 3, 5 (1934) 291-299. (276) S. A. Watson and R. L. Whistler, Ind. Eng. Chem., Anal. Ed., 18 (1946) 75-76. (277) R. M. McCready and W. Z. Hassid, J. Am. Chem. SOC.,65 (1943) 1154-1157. (278) I. A. Wolff, L. J. Gundrum, and C. E. Rist, J. Am. Chem. SOC.,72 (1950) 5188-5191. (279) G. L. Ciottoli Sollazzo, Tec. Molitoria, 17 (1966) 121-124. (280) Y. Otani and S. Takahashi, Hakko Kagaku Zasshi, 36 (1958) 453-457: Chem. Abstr.. 53 (1959) 17416. (281) E. J. Bourne. W. N. Haworth, M. Stacey, and S. Peat, J. Chem. SOC., (1948) 924-930. (282) Y. Kihara and Z. Kawase, Rept. Food Res. Inst., 5 (1951) 27-34; Chem. Abstr., 49 (1955) 16482. (283) S. Augustat, Ernaehrungsforsch., 3 (1958) 567-574. (284) L. H. Lampitt. C. H. F. Fuller, and N. Goldenberg,J. Chem. SUC.Ind., 60 (1941) 99-1 11. (285) M. Samec and M. Dermelj, Kolluid-Z., 101 (1942) 123-126. (286) E. Nielsen, Nature, 194 (1962) 89-90. (287) S. Rogols and R. L. High, Staerke, 15 (1963) 1-4. (288) K. Takaoka, Nippon Nogei Kagaku Kaishi, 23 (1949) 56-60. (289) K. Takaoka, Mern. Inst. Sci. Ind. Res. Osaka Univ., 7 (1950) 159-162. (290) B. W. Smith and J. H. Roe, J. Biol. Chem., 179 (1949) 53-59. (291) M. J. Murphy, J. Chromatogr., SO (1970) 539-540. (292) Konishiroku Photo Ind. Co. Ltd.,Jpn Kokai Tokkyu Koho J P 59,224,698 (1984); Chem. Abstr., 102 (1985) 162974~. (293) Shu Shyang Kuo and Teng Yung Feng, Anal. Biochem., 177 (1989) 165-167. (294) J. Hollo, J. Szejtli, and G. S. Gantner, Period. Polytech., 3 (1959) 95-104. (295) J. Hollo, J. Szejtli, and G. S. Gantner, Period. Polytech., 3 (1959) 163-172. (296) M. A. Rutschmann and J. Solms, Lebensm. Wiss. Technol., 23 (1990) 88-93. (297) J. Szejtli, M. Richter, and S. Augustat, Biopolyrners. 5 (1967) 5-16. (298) G. G. Du Chatelier, Ann. Pharm. Fr., 8 (1950) 644-649. (299) J. Hollo and J. Szejtli, Staerke, 14 (1962) 75-78. (300) K. Ohashi, Nippon Nogei Kagaku Kaishi, 33 (1958) 576; Staerke, 15 (1963) 34. (301) 0. Yu.Magidson, Zh. Khim. Prom., 4 (1927) 3-8. (302) G. E. M. A., Vienne, Fr. Pat. 945,359 (1949): Chem. Abstr., 45 (1951) 4010. (303) A. Lumiere, C. R. Acad. Sci., 165 (1917) 376-377. (304) P. Boa, Pharm. J., 94 (1915) 485-486.501. (305) J. A. 0. Johansson, Swedish Pat. 405,680 (1978): Chem. Abstr., 90 (1979) 210138k. (306) S. Yamamoto and Y. Yamamoto, Japanese Pat. 8899(’57)(1958); Chem. Abstr., 52 (1958) 12334. (307) V. 0. Mokhnach, M. A. Litvinov, L. B., Borisov, N. A., Matyko, and M. 1. SmirnovaIkonnikova, Mikobiologiya, 29 (1960) 451-452. (308) V. 0. Mokhnach, L. B. Borisov, M. A. Litvinov, and N. A. Matyko, Tr. Leningr. Sunit.Cigen. Med. Inst., 66 (1962) 162-170. (309) V. 0. Mokhnach and L. N. Propp, Iodinol Med. Vet., Eksp. Klin. Issled. Akad. Nauk SSSR, Bot. Inst. (1967) 21-31.

COMPLEXES OF STARCH WITH INORGANIC GUESTS

335

(310) N. Ya. Aliev, K. K. Rakhimov, V. V. Alferov, and T. Pulatov, Tr. Uzb. Nauch.-lssled. Inst. Vet., 21 (1973) 241-243; Chem. Abstr., 82 (1975) 39339k. (311) A. F. Kirizhnu, P. G. Tatarov, E. L. Rudenko, and S. S. Pyslarach, Fizikokhimicheskiye aspekti tekhnologii pishchevikh produktov, Kishinev, 1985, p. 48-50; Ref:Zh., Khim. (1985) 16R182. (312) V. 0. Mokhnach, E. R. Popova, and F. Kh. Yakhina, Iodinol Met. Vet., Eksp. Klin. Issled., Akad. Nauk SSSR, Bot. Inst., (1967) 145-149. (313) V. I. Zak, L. E. Olifson, and L. E. Mikhailova, Mikroelem. Biosfere Promen. Ikh Sel. Khoz. Med. Sib. Dalnego Vostoka, Dokl. Sib. Konf: 3rd, 1969, (1971) 451-455; Chem. Abstr., 79 (1973) 124783h. (314) R. Leskova, Wien. Tierazrl. Monatsschr., 56 (1969) 369-374. (315) E. R. Popova, V. V. Kovalev, and Ya. R. Krutyi, Upr. assortimentom i kachestvom rovarov v torgovle, Kiev (1987) 73-76; Ref: Zh., Khim. (1987) 23R130. (316) E . R. Popova, Puti sokhraneniya kachestva i snizheniya poter tovarov v torgovle., Sb. Nauch. Tr., Kiev, (1990) 54-63; Ref: Zh., Khim. (1990) 21R1234. (317) N. N. Apalkova, Sadovod. Vinograd. Mold. (9) (1988) 43-45. (318) E. R. Popova, N. V. Tirnoshenko, and M. I. Chupa, Sokhrmeniye kachestva optimiz. assortimenta isnizheniyepoter tovarov v torgovle, Kiev (1989) 118-121; Ref: Zh., Khim., (1989) YR1473. (319) L. A. Nikulina, S. M. Zubkova, Yu. N. Korolev, A. S. Bobkova, and E. G. Korovkina, Radiobiologiya, 300 (1990) 417-419. (320) F. R. Smith, PCT Int. Appl. WO 85 02,422 (1985); Chem. Abstr., 104 (1986) 70266f. (321) P. Collings. Eur. Pat Appl. E P 391,542 (1989); Chem. Abstr., 114 (1991) 26050~. (322) M. T. Rahmatalla, A. Abdel-Kerim, and N. El-Mashatt, Iraqi J. Sci., 31 (1990) 484-498 Chem. Abstr., 114 (1991) 105686d. (323) D. J. Macchia and F. A. Bettelheim, J. Polym. Sci., B 2 (1964) 1101-1104. (324) G. Nemitz, Staerke, 14 (1962) 276-278. (325) P. H. Thorpe, Appita, 35 (1982) 505-510. (326) J. Muetgeert, P. Hiernstra, and W. C. Bus, Staerke, 10 (1958) 303-308. (327) A. V. Rakovskii, D. N. Tarassenkov, and A. V. Komandin, Zh. Obshch. Khim., 5 (1935) 1441-1444. (328) F. Schierbaurn, Staerke, 12 (1960) 237-243. (329) S. Nara, K. Yamaguchi, and K. Okada, Denpun Kogyo Gakkaishi, 16 (1968) 1-4; Chem. A bstr., 70 (1969) 116425s. (330) S. Nara, Denpun Kugaku, 28 (1981) 24-32; Chem. Abstr., 94 (1981) 193980s. (331) A. Rakowski. Kolloid-Z., 9 (1911) 225-230. (332) A. Rakowski, Kolloid-Z., 10 (1912) 22-31. (333) A. Rakowski, Kolloid-Z., 11 (1912) 269-272. (334) G. Centola, Atti Ricerca Sci. Acad. Lincei, Rend., [6] 23 (1936) 617-622. (335) S. P. Chesheva, Kolloid. Zh., 3 (1937) 121-127. (336) T. A. Granskaya and N. J. Ssakun, Kolloid. Zh., 3 (1937) 117-121. (337) G. Malfitano and A. N. Moschkoff, C. R. Acad. Sci., (1910) 710-711; 151 (1910) 817-819. (338) J. van der Hoeve, H. G. Bungenberg de Jong, and H. R. Kruyt, Kolloid Beih., 39 (1934) 105-123. (339) M. Samec, Kolloid Beih., 54 (1943) 435-483. (340) A. V. Dumanskii, Kolloid-Z., 65 (1933) 178-184. (341) A. V. Dumanskii, Dokl. Akad. Nauk SSSR, 64 (1949) 537-540. (342) A. V. Dumanskii and Ye. A. Yakovkina, Kolloid. Zh., 14 (1952) 37-39. (343) G. Champetier and D. Yovanovitch, C. R. Acad. Sci., 234 (1952) 837-839. (344) 0. Yavanovitch. C. R. Acad. Sci., 240 (1955) 429-431.

336

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

W. Nossian, J. Prukt. Chem., 83 (1861) 41-50. M. Ulmann, Ernuehrungsforsch., 1 (1956) 96-104. F. Schierbaum, K. Taeufel, and M. Ulmann, Stuerke, 14 (1962) 161-167. F. Schierbaum, Stuerke, 12 (1960) 257-265. M. V. Chapek, A. A. Mozgovoy, and G. N. Tretyakov, Kolloid. Zh., 1 (1935) 399-416. M. V. Chapek and P. V. Zhuravel, Pedologiyu, (11) (1939) 35-43. N. I. Gumayunov, L. Yu. Vasileva, and V. M. Koshkin, Biofiziku, 20 (1975) 38-40. M. P. Volarovich, N. I. Gamayunov, and L. Yu. Vasileva, Kollod. Zh., 33 (1971) 922-923. P. Tomasik, M. Baczkowicz, and S. Wiejak, Stuerke, 38 (1986) 410-413. S. L. Gupta and R. K. S. Bhatia, Indian J. Chem., 7 (1969) 1231-1233. M. Baczkowicz, P. Tomasik, and S. Wiejak, Stuerke, 38 (1986) 339-341. M. Ulmann and F. Schierbaum, Stuerke, 9 (1957) 23-29. F. Schierbaum and K. Taeufel, Stuerke, 14 (1962) 411-415. F. Schierbaum and K. Taeufel, Stuerke, 14 (1962) 274-276. N. N. Hellman, T. F. Boesh, and E. H. Melvin, J. Am. Chem. SOC., 74 (1952) 348-350. L. P. Kaminskii, V. V. Beldii, V. P. Dushenko, B. S. Sazhin, and M. S . Panchenko, Khim. Nuft. Mushinostr., (1) (1970) 6-8. (361) S. Poliszko, G. Hoffmann, and R. Rezler, Actu Aliment. Pol., 17 (1991) 351-359. (362) T. M. Shaw and R. H. Elsken, J. Chem. Phys., 21 (1953) 565-566. (363) C. F. S. Van der Berg, J. A. G. Kaper, and I. Wo1ters.J. Food Technol., 10 (1975) 589-602. (364) S. F. Tanner, B. P. Hills, and R. Parker, J. Chem. Soc., Furuduy Trans., 87 (1991) 26132621. (365) H. Lechert, W. C. Scoggins, W. D. Bassler, and J. Schwier, Stuerke, 40 (1988) 245-250. (366) R. Hoover and D. Hadzijev, Stuerke, 33 (1981) 290-300. (367) M. Shikata and S. Ueda, J . Electrochem. Assoc., Jpn., 5 (1937) 438-448. (368) P. Abadie, R. Charbonniere, A. Gidel. P. Girard, and A. Guilbot, J. Chem. Phys., 54 (1957) 235-238. (369) S. Ono, T. Kuge, and N. Koizumi, Bull. Chem. SOC. Jpn., 31 (1958) 34-39. (370) A. Guilbot, R. Charbonniere, P. Abadie, and P. Girard, Stuerke, 12 (1960) 327-332. (371) F. Horii, H. Yamamoto, A. Hirai, and B. Kitamaru, Curbohydr. Res., 160 (1987) 29-40. (372) J. R. Katz and J. C. Derksen, Z. Phys. Chem., A 150 (1930) 100-109. (373) J. R. Katz, Kolloidchemie der Stuerke, Steinkopf, Dresden, 1927, p.74. (374) A. Guilbot, R. Charbonniere, and R. Drapron, Stuerke, 13 (1961) 204-207. (375) C. Legrand and 0. Yovanovitch, C. R. Acud. Sci., 245 (1957) 1553-1556. (376) V. Hain, H. Bizot, and A. Buleon, Curbohydr. Polym., 5 (1985) 91-106. (377) A. Buleon, H. Bizot, M. M. Delage, and J. L. Multon, Stuerke, 334 (1982) 361-366. (378) V. M. Irklei, T. P. Starunskaya, N. I. Bychkovskii, I. D. Kolpakova, and M. P. Nosov, Khim. Voloknu, (4) (1983) 28-29. (379) E. Kudla and P. Tomasik, Stuerke, 44 (1992) 253-260. (380) A . G. Assef, R. H. Haas, and C. B. Purves, J. Am. Chem. Soc., 66 (1944) 66-73. (381) D. E. Wursker, G. E. Peck, and D . 0. Kildsig, Stuerke, 36 (1984) 294-299. (382) J. Szejtli and S . Augustat, Stuerke, 18 (1966) 38-52. (383) P. C. Manor and W. Saenger, J. Am. Chem. Soc., 96 (1974) 3630-3639. (384) G. Rappenecker and P. Zugenmaier, Curbohydr. Res., 89 (1981) 11-19. (385) W. Banks and C. T. Greenwood, Stuerke, 23 (1971) 300-314. (386) E. I. Zhuravleva, Kolloid. Zh., (1948) 203-208. (387) E. Farrow and E. Swan, Shirley Inst. Mem., 2 (1923) 329-338. (388) E. Swan, J. Text. Inst., 17T (1926) 527-538. (389) B. Ubertis and G. Roversi, Stuerke, 10 (1958) 266-267. (390) W. Bushuk and C. A. Winkler, Cereal Chem., 34 (1957) 73-86.

(345) (346) (347) (348) (349) (350) (351) (352) (353) (354) (355) (356) (357) (358) (359) (360)

COMPLEXES OF STARCH WITH INORGANIC GUESTS (391) (392) (393) (394)

337

W. Poersch, Sfuerke, 15 (1963) 405-412. A. H. A. de Willigen and P. W. de Groot, Sfuerke, 19 (1967) 368-372. M. Freymann and R. Freymann, J. Phys. Radium, 15 (1954) 165-175. M. Loncin, J. Lenges, J. J. Bimbenet, and D. Jacqumain, Ind. Aliment. Agr. (lnd. Aliment. Agr. (Paris), 82 (1965) 923-927. (395) G. A. Egorov and A. 1. Shchegoleva, Izv. Vyssh. Uchebn. Zuved., Pishch. Tekhnol. (4) (1974) 16-18. (396) E. D. Sunner, W. K. Poole, D. N. Entrekin, and A. F. Ike, J. Phurm. Sci., 58 (1969) 83-86. (397) C. A. Brownic, J . Ind. Chem. Eng., 14 (1922) 712-714. (398) E. I. Zhuravleva, Kolloid. Zh., 12 (1950) 32-35. (399) A. R. Urqhart, J. Text. Inst., 20T (1929) 125-132. (400) F. T. Pierce, Shirley Inst. Mem., 8 (1929) 35-52. (401) W. Bushuk and C. A. Winkler, Cereal Chem., 34 (1957) 87-93. (402) D. E. Wurster, G. E. Pock, and D.0. Kildsig, Stuerke, 36 (1984) 294-299. (403) N. Koizumi and S . Ono, Bull. Inst. Chem. Res. Kyofo Univ., 20 (1950) 47-48. (404) N. Koizumi, S. Ono, and T. Kuge Bull. Insf. Chem. Res. Kyoto Univ., 20 (1950) 80. (405) M. P. Volarovich, N. I. Gamayunov, and L. Yu. Vasilev, Kolloid. Zh., 37 (1975) 345-348. (406) K. Kamiyashi, M. Freymann, and M. J. Ripoche, Arch. Sci. (Genovu), 11 (1958) 71-73. (407) S. Nara, Y. Yabumoto, K. Yamaguchi, and I. Maeda, Nippon Nogei Kuguku Kuishi, 43 (1969) 570-574; Chem. Abstr., 65 (1966) 11236. (408) A. S. Ginzburg, I. M. Savina, and Yu. Z. Altshuter, 44(12) (1970) 55-57. (409) W. D. Cramer. T. P. Hanson. G. T. Tsao, and E. B. Lancaster, J. Mucromol. Sci., Phys., 3 (1969) 611-622. (410) W. D. Cramer, G . T. Tsao, and E. B. Lancaster, Polym. P r e p . Am. Chem. Soc., Div. Polym. Chem., 9 (1968) 1473-1480. (411) S . Tomita and K. Terajima, Nippon Nogei Kuguku Kuishi, 44 (1970) 111-117; Chem. Abstr., 73 (1970) 26857s. (412) Liang Tsen Fan, Huai-Chong Chen, J. A. Shellenberger, and Do Sup Chung, Cereal Chem., 42 (1965) 387-398. (413) P. J . Carrillo, S. G. Gilbert, and H. Denn, J. Food Sci., 53 (1988) 1199-1203. (414) E. Swan, Shirley Inst. Mem., 5 (1926) 167-176. (415) M. K. S. Morsi, C. Sterling, and D. H. Volman,J. Appl. Polyrn. Sci., 11 (1967) 1217-1225. (416) D. H. Volman. 1. W. Simons, J. R. Seed, and C . Sterling,J. Polym. Sci., 46 (1960) 355-364. (417) V. Rebar, E. R. Fischbach, D. Apostolopulos, and J. L. Kokini, Biotechnol. Bioeng., 26 (1984) 513-517. (418) C. Tsutsumi and H. Koizumi, Shokuryo Kenkyusho Kenkyu Hokoku, 21 (1966) 1-5; Chem. Absfr., 65 (1966) 11236. (419) J. R. Katz, Kolloid Eeih., 9 (1917) 65-182. (420) L. Sair and W. R. Fetzer, Itid. Eng. Chem., 36 (1944) 205-208. (421) F. El-Khawas. R. Tawashi, and H. Czetsch Lindewald, J. SOC.Cosmetic Chem., 17 (1966) 103-1 14. (422) L. Smolina, Tr. Tashkent. Selskokhoz. Insf., (7) (1956) 189-195. (423) T. P. Hanson, W. D. Cramer, W. H. Abraham, and P. E. Lancaster, Chem. Eng. Progr. Symp. Ser., 67 (1971) 35-39. (424) A. J. Stamm, Tuppi, 40 (1957) 765-770. (425) N. N. Hellman and E. H. Melvin, J. Am. Chem. SOC.,72 (1950) 5186-5188. (426) F. Schierhaum and K. Taeufel, Stuerke, 14 (1962) 233-238. (427) C. A. Winkler and W. F. Geddes, Cereal Chem., 8 (1931) 455-474. (428) W. F. Geddes, Food Ind., 4 (1932) 243. (429) H. Rodewald, Z. Physik. Chem., 33 (1900) 593-604.

338

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

(430) H. Rodewald and A. Kattein, Z. Physik. Chem., 33 (1900) 579-592. (431) H. Gaudechon, C. R. Acad. ScL, 157 (1913) 209. (432) W. G. Schrenk, A. C. Andrews, and H. King, Ind. Eng. Chem., 39 (1947) 113-1 16. (433) A. V. Dumanskii and J. F. Nekryach, 17 (1955) 168-170; 171-172. (434) S. M. Lipatov, B. A. Karzownik, and M. S. Shulman, Kolloid. Zh., 12 (1950) 286-293. (435) M. Ulmann, Stuerke, 5 (1953) 290-296. (436) R. Brebant, Inds. Agr. Aliment. (Paris), 66 (1949) 141-153. (437) A. L. Elder and T. J. Schoch, Cereal Sci. Today, 4 (1959) 202-208. (438) F. Schierbaum and M. Ulmann, Stuerke, 9 (1957) 48-50. (439) W. Maurer, Staerke, 7 (1955) 56-64. (440) N. N. Hellmann and E. H. Melvin, Cereal Chem., 25 (1948) 148-150. (441) E. Eberius, Stuerke, 9 (1957) 77-81. (442) 0. A. Dumanskii and E. A. Yakovkina, Tr. Kievsk. Tekhnol. Inst. Pishch. Prom., 27 (1963) 101-104. (443) M. Boruch, S. Brzezinski, and A. Palka, Acta Aliment. Pol., 11 (1985) 115-124. (444) M. E. Freeman, Arch. Biochem., 1 (1942) 27-39. (445) B. Das, R. K. Sethi, and S. L. Chopra, lsr. J. Chem., 10 (1972) 963-965. (446) M. Ulman and F. Schierbaum, Staerke, 8 (1956) 81-87. (447) G. A. Sorokin, Vysokomol. Soedin., 13 (1971) 608-612. (448) M. V. Chapek, Kolloid-Z., 67 (1934) 145-148. (449) N. Koda, Acta Schol. Med. Univ. Imp. Kyoto, 10 (1928) 137-154 Chem. Abstr., 22 (1928) 2790-2791. (450) H. Schlenk, D. M. Sand, and J. A. Tillotson, U.S. Pat. 2,827,452 (1958); Chem. Abstr., 52 (1958) 12901. (451) F. Cramer and M. Henglein, Chem. Ber., 90 (1957) 2561-2571. (4.52) V. V. Rachinskii, A. Peltser, and T. A. Khegai, Izv. Timiryuzevski. S-kh. Akad., (5) (1981) 153-156. (453) P. Rion and P. A. Berard. C. R. Acad. Sci., 186 (1928) 1433-1436. (454) S. Kiki, R e p . Centr. Lab. S. Manchuria Railway Co., (1929) 24-6; Chem. Abstr., 25 (1931) 1702. (455) D. Costa, Gazz. Chim. Ital., 54 (1924) 207-211. (456) 1. F. Karpova and E. V. Kazakov, Izv. Vyssh. Uchebn. Zaved., Pishch. Tekhnol., (2) (1964) 21-23. (457) C. Fuehrer and M. Rebentisch, Pharm. Ind., 37 (1975) 441-446. (458) R. Taft, Trans. Kansas Acad. Sci., 32 (1929) 38-41. (459) J. Chociej. A. Konitz, and P. Tomasik, Acfa Aliment. Pol., 11 (1983) 36-42. (460) P. M. Afenya, Int. J. Miner. Process, 9 (1982) 303-319. (461) S. R. Belajee and 1. Iwasaki. Trans. AIME, (1969) 401-406: Chem. Abstr., 73 (1970) 90217k. (462) A. V. Rakovskii, Zh. Russ. Khim. Obshch., 44 (1912) 586-605. (463) H. Lloyd, J . Am. Chem. Soc., 33 (1911) 1213-1226. (464) L. T. Smith and S. G. Morris, lnd. Eng. Chem., 36 (1944) 1052-1054. (465) L. 0. Gill, Staley J., 9 (1927) 5-13. (466) A. Rakowski, Kolloid-Z., 11 (1912) 51-58. (467) A . V. Rakovskii, Zh. R i m . Fiz. Khim. Obshch., 45 (1913) 13-21. (468) A. Rakowski, Kolloid-Z., 12 (1913) 177-181. (469) A. Reychler. Bull. Soc. Belg. Chim., 23 (1910) 378-383. (470) 0. Yovanovitch, C. R. A d . Sci.,232 (1951) 1833-1835. (471) G. Champetier and 0. Yovanovitch, J. Chim. Phys., 48 (1951) 587-589. (472) S. Lipatov, Kolloid-Z., 39 (1926) 9-14.

COMPLEXES O F STARCH WITH INORGANIC GUESTS

339

(473) S. Lipatov, Zh. Russ. Fiz. Khim. Obshch., 58 (1926) 983-993. (474) I. S. Lipatov, 2. Anorg. Allgem. Chem., 152 (1926) 73-90. (475) V. 1. Deulin, USSR Pat. 272,908 (1970); Chem. Abstr., 73 (1970) 111197~. (476) A. H. A. de Willigen and P. W. de Groot, Stuerke, 23 (1971) 37-42. (477) A. Rakowski, Kolloid-Z., 12 (1913) 128-130. (478) H. W. Leach, T. J. Schoch, and E. F. Cheesman, Staerke, 13 (1961) 200-203. (479) H. Ivekovic. T. Vrbaski, and D. Pavlovic, Croat. Chem. Acta, 28 (1956) 101-105. (480) T. Sato, Nuturwissenschufren, 45 (1958) 184. (481) A. V. Rakovskii, Zh. Russ. Fiz. Khim., 46 (1914) 246-258. (482) E. J. Bourne. G. H. Donninson, S. Peat, and W. J. Whelan, J. Chem. Soc., (1949) 1-5. (483) M. Kuchikata, Y. Nitta, and H. Kuza, Jpn. Kokui Tokkyo Koho, 79.160,721 (1979); Chem. Abstr., 92 (1980) 175796r. (484) A. M. A. de Willigen, Profestu Audupelverwek (Groningen), Kurt. Ber., 28 (May 1950); Chem. Abstr., 44 (1950) 9173. (485) A. F. Belogurova, A. B. Lukyanov, and B. A. Veksler, Sukh. Prom., 41 (8) (1967) 75-77. (486) M. Patasinski, Actu Agr. Silv., Ser. Roln., 4 (1964) 151-166. (487) M. Patasinski and J. Busek, Rocz. Technol. Chem. Zywn., 47-57. (488) R. Haller, Melliund Textilber., 31 (1950) 49-50. (489) J. Dykyj, Chem. Lisfy, 38 (1944) 219-226. (490) J. Seidemann, Staerke-Atlas, Paul Parey, Berlin, 1966, 77-91. (491) E. B. Lancaster and H. F. Conway, Cereal Sci. Today, 13 (1968) 248-250. (492) 8. M. Gough and J. N. Pybus, Staerke, 25 (1973) 129-130. (493) J. R. Katz, J. Seiberlich, and A. Weidinger, Biochem. Z., 298 (1938) 320-322. (494) H. Courtonne, C. R. Acud. Sci., 171 (1920) 1168-1170. (495) A. Buzagh. Kolloid-Z., 103 (1943) 119-126. (496) J. 0. Samuel. J. Inst. Fuel., 24 (1951) 238-247. (497) L. C. Hoffpauir and J. D. Guthrie, J. Am. Chem. Soc., 67 (1945) 1225-1226. (498) I. D. Popov and A. Dushev, Izv. Insr. Mefodii Popov. Bulg. Akad. Nauk, 9 (1958) 175- 187. (499) J. L. Jane. Stuerkr, 45 (1993) 172-175. (500) J. L. Jane, Staerke, 45 (1993) 161-166. (501) A. Reychler, Bull. Soc. Chim.Belg., 30 (1921) 223-225. (502) A. Reychler, Bull. Soc. Chim. Fr., [4] 29 (1921) 311-316. (503) A. Reychler, Bull. SOC. Chim. Belg., 29 (1920) 118-122. (504) J. P. Katz and F. J. F. Muschter, Biochem. Z., 257 (1933) 385-396. (505) R. Collinson and M. P. McDonald, Nature (London), 136 (1960) 548. (506) R. Collinson, Nature (London), 188 (1960) 1105. (507) R. Collinson, Staerke, 16 (1964) 184-186. (508) H. J. Hennig and P. Scholz, 2. Phys. Chem., (Frankfurt), 103 (1970) 31-44. (509) J. P. Katz and F. J. F. Muschter, Biochem. Z., 257 (1933) 397-405. (510) P. Moretti and G. Muscolino, Arch. Furmacol. Sper., 51 (1930) 167-171. (511) B. Novak and S. Franklova, Zentr. Bukteriol. Purasifenk. Abt. 11, 117 (1964) 714-721. (512) M. 1. Knyaginchv. Kolloid. Zh., 5 (1939) 899-906. (513) A. Delauney and C . de Roquefeuil, Rev. Immunol., 19 (1955) 46-51. (514) R. H. Harris and 0. Banasik, Food Res., 13 (1948) 70-81. (515) J. Szejtli, Cyclodextrins and Their Inclusion Complexes, Akademiai Kiado, Budapest, 1982. (516) S. R. Erlander and R. Tobin, Mukromol. Chem., 111 (1968) 212-225. (517) S. Saito, Kolloid-Z., 154 (1957) 19-29.

340

PlOTR TOMASIK AND CHRISTOPHER H. SCHILLING

(518) M. Kugimiya and K. Mukai, Denpun Kugaku 36 (1989) 249-2.55; Chem. Absfr., 112 (1990) 181768f. (519) W. A. Mitchell, W. C. Seidel, and J. D. O’Rurke, Eur. Patent Appl. 11,479 (1980); Chem. Abstr., 93 (1980) 130970~. (520) P. Somasundaran, J. Colloid Interface Sci., 31 (1969) 557-565. (521) F. Fischler and S. Schwaibold, Biochem. Z., 283 (1936) 322-338. (522) E. Stern, British Pat. 272,274 (1926); Chem. Ahsrr., 22 (1928) 1872. (523) N. Perisic-Janjic, V. Camic, and S. Radosavljevic, Chromutograhiu, 57 (1983) 454-455. (524) V. D. Canic and N. Perisic-Janjic, Glus. Hem. Drus. Beogrud., 34 (1969) 535-539; Chem. Absrr., 74 (1971) 15976r. (525) M. Dugandzic, Z. Koricanac, and L. Milovanovic, Arh. Farm., 22 (1972) 159-161. (526) C. Calzolari, L. Favretto, and G. Bruni, Univ. Srudi Trieste, Fuc. Econ. Commer. Ist Merceol., 26 (1965); Chem. Absrr., 67 (1967) 76518d. (527) W. Biedermann, Biochem. Z., 137 (1923) 35-42. (528) W. Biedermann, Biochem. Z., 149 (1924) 309-328. (529) M. Hoehn. Biochem. Z., 135 (1923) 587-602. (530) N. Malyshev, Biochern. Z., 206 (1929) 401-409. (531) L. S. Solomina, E. A. Shtyrkova, and N. N. Tregubov, Sukh. Prom., (3) (1979) 40-42. (532) M. 1. Knyaginichev and Yu R. Bolkhovitina, Izv. Vyssh. Uchebn. Zuved., Pishch. Tekhno/., (4) (1964) 47-48. (533) L. B. Smolina, Ukr. Khim. Zh., (1950) 485-495. (534) I. D. Popov and L. Doganova-Koleva, Izv. Inst. Metodii Popov. Bulg. Akud. Nuuk, 9 (1958) 189-196. (535) J. van der Hoeve, H. G. Bungenbreg de Jong, and H. R. Kruyt. Kolloid Beih., 39 (1934) 124-138. (536) J. H. C. Merckel, Kolloid-Z., 75 (1936) 318-322. (537) E. H. Buechner, E. M. Bruins, and J. H. C. Merckel, Proc. Acud. Sci. Amsterdam, 35 (1932) 569-575. (538) A. Boutriac and M. Chapeaux, C. R. Acad. Sci., 214 (1942) 949-950. (539) D. G. Medcalf and K. A. Gilles, Stuerke, 18 (1966) 101-105. (540) K. Takahashi, K. Shira, K. Wada, and A. Kawamura, Denpun Kugukci, 27 (1980) 22-27; Chem. Ahsrr., 9.5 (1942) 949-950. (541) T. Shimizu, Kogyo Kaguku Zusshi, 64 (1961) 677-682; Chem. Absrr., 57 (1962) 7502. (542) C. Drotschmann, Butterien, 16 (1963) 426-432. (543) K. Heyns and F. Burchard, Stuerke, 2 (1950) 293-296. (544) D. T. Yu and M. M. McMasters, Stuerke, 17 (1965) 75-77. (545) R. E. Baker and M. M. MacMaster, Sruerke, 19 (1967) 399-402. (546) H. Kober and F. Dittmar, Kolloid-Z., 73 (1935) 219-226. (547) J. 0. Samuel, J. Inst. Fuel, 24 (1951) 196-206. (548) S. E. Kharin, R. Jasiunas, and Z. P. Shcherban, in A. V. Zubchenko (Ed.), Fizzcheskokhimicheskiye osnovipishchevoi thekhnologii, Voronezhskij Tekhnologicheskij Institut. Voronezh, USSR, 1973, 142-146. (549) J. A. Rendleman, Food Chem., 3 (1978) 47-162. (550) A. Findley and C. Rosebourne, J. Soc. Chem. Ind., 41 (1922) 58T-9T. (551) T. J. Schoch and E. C. Meinwald, Anal. Chem., 26 (1956) 382-387. (552) A. I. Zhushman, E. K. Koptelova, and N. M. Popova, Zesz. Probl. Podsr. Nuuk Roln., 159 (1974) 177-186. (553) Henkel and Cie. GmbH, German Pat. 1,079 831 (1960); Chem. Abstr., 55 (1961) 1907s. (554) M. E. Demoussy, C. R. Acud. Sci., 142 (1906) 933-935. (555) K. Sheringa, Phurm. Weekbl. 57 (1920) 1289-1294.

COMPLEXES O F STARCH WITH INORGANIC GUESTS

341

J. Huebner and K. Venkataraman, J. Soc. Dyers Colourists, 42 (1926) 110-121. R. B. Patel and H. A. Turner, J. SOC.Dyers Colourists, 68 (1952) 77-87. Henkel et Cie. Ges., British Par. 289,053 (1927); Chem. Absrr., 23 (1929) 681. A. Hering Aktiengesselschaft, German Pat. 811,460 (1952); Chem. Abstr., 47 (1953) 12853. (560) I. D. Evans and D. R. Heisman. Staerke, 34 (1982) 224-231. (561) 0. B. Wurzburg and L. H. Kruger, U.S. Pat. 3,977,897 (1976); Chem. Absrr., 85 (1976) 162291~. (562) Pennsalt Chemicals, German Pat. 1,146,820 (1963); Chem. Abstr., 59 (1963) 2999f. (563) International Minerals and Chemical Corp. British Pat. 857,868 (1961); Chem. Abstr., 55 (1961) 13887. (564) G. N. Gupta and K. C . Mukherji, J. Sci. Technol. (Kampur, India), 9 (1949) 17-27. (565) J. Hollo. J. Huszar, J. Szejtli, and M. Petho, Staerke, 14 (1962) 343-347. (566) L. H. Hood and G. K. O’Shea, Cereal Chem., 5 (1977) 266-271. (567) S. J . Przylecki, Spr. Posiedz. Tow. Nauk. Warszawa, Cl.IV, 29 (1936) 186-187. (568) W. C. Bus, J. Muetgeert. and P. Hiemstra, US Par. 2,829,988 (1958); Chem. Abstr., 52 (1958) 14204. (569) N. A. Smykova and B. N. Stepanenko, Prikl. Biokhim. Mikrobiol., 5 (1969) 219-220. (570) C. Mannich and K. Lenz, 2. Nahr. Genussrn., 40 (1920) 1-11. (571) M. Boruch, Zesz. Probl. Post. Roln., 159 (1974) 205-210. (572) D. L. Lynch, L. M. Wright, and L. J. Cotnoir, Soil Sci. Soc. Am., Proc., 20 (1956) 6-9. (573) G. Sukan, M. W. Kearsley, and G. G . Birch. Staerke, 31 (1979) 125-128. (574) W. L. Craig, U.S. Pat. 2,824,099 (1958); Chem. Abstr., 52 (1958) 17752. (575) G. T. Bravos and J. W. Evans, US.Pat. 2,900,335 (1959); Chem. Abstr., 53 (1959) 22872. (576) J. R. Fraser and R. A. Hoodless, Analyst, 88 (1963) 558-560. (577) G. Pfeiffer, German Pat. 1,099,468 (1957); Chem. Abstr., (1960) 12424. (578) M. M. Nurkas, Poligr. Proizv. (5/6) (1946) 19-20. (579) J. Asboth, Chem. Zrg., 11 (1887) 147-148. (580) J. C. Lintner, Ber., 21 (1888) 454c. (581) P. Karrer, C. Naegli, 0. Hunvitz, and A. Waelti, Helv. Chim. Acra, 4 (1921) 678-699. (582) E. Stern, Z. Angew. Chem., 41 (1928) 88-91. (583) K. Romaszeder, Mugy. Textiltech., 23 (1971) 276-283. (584) R. Murakami, Kobunshi Ronbunshu, 43 (1986) 389-93; Chem. Absrr., 105 (1986) 99455~. (585) R. Murakami, Kenkyu Hokoku-Kurnamofo Kogyo Daigaku, 10 (1985) 63-65; Chem. Absrr., 103 (1985) 162118s. (586) R. Murakami, Kenkyu Hokoku-Kumamoto Kogyo Daigaku, 11 (1986) 97-100; Chem. Abstr., 105 (1986) 62548~. (587) D. Trimnell, B. S. Shasha, R. E. Wing, and F. H. Otey,J. Polym. Sci., 27 (1982) 3919-3928. (588) R. L. Jones, U S . Pat. 2,935,377 (1960); Chem. Abstr., 54 (1960) 16356. (589) R. Murakami, Denpun Kagaku, 36 (1989) 273-276; Chem. Absrr., 112 (1990) 181770a. (590) R. Murakami, Kenkyu Hokoku - Kumamoto Kogyo Daigaku, 7 (1982) 57431; Chem. Absrr., 97 (1982) 57431. (591) Henkel et Cie. Ges., British Par. 294,235 (1927); Chem. Abstr., 23 (1929) 2065. (592) W. L. Craig, U S . Pat. 2,425,058 (1947); Chem. Absrr., 41 (1947) 7138. (593) W. L. Craig, U S . Pat. 2,457,797 (1949); Chem. Abstr., 57 (1962) 9966n. (594) J. W. Todd, U.S. Pat. 2,865,775 (1958); Chem. Abstr., 43 (1949) 2006. (595) R. F. Davies and B. H. Erleau, German Pat. 2,814,474 (1978); Chem. Absrr., 90 (1979) 7969q. (596) H. McIver, Adhesives & Resins, 4 (4) (1956) 50-59. (597) J. L. Miller, U.S. Pat. 2,999,761 (1959); Chem. Abstr., 56 (1962) 2624.

(556) (557) (558) (559)

342

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

(598) J . W. Evans and G. E. Nelson, US Put. 3,083,112 (1963); Chem. Abstr., 59 (1963) 1829. (599) F. Trost, Ind. Chim., 4 (1929) 868-869. (600) E. H. Fisher and W. Settele, Helv. Chim. Acru, 36 (1953) 811-819. (601) M. Ulmann and B. Wendt, Kolloid-Z., 148 (1956) 157-168. (602) M. Ulrnann, Stuerke, 4 (1952) 73-77. (603) T. Sato, J. Appl. Chem. (London), 10 (1960) 35-38. (604) I. Dvornik and Z. E. Hermann, Kolloid-Z., 128 (1952) 75-86. (605) M. L. Cushing, Pulp Paper Mug. Can., 55 (1954) 163-165. (606) T. Aitken, W. V. Cross, and F. W. Webking, US Parent 3,264,174 (1966); Chem. Absrr., 65 (1966) 12409. (607) V. D. Ponomarev and L. G. Romanov, Vestn.Akud. Nuuk Kuz. SSR., 18 ( 5 ) (1962)57-60. (608) N. Rama and E. Jaekko, U.S. Pat. 3,455,715 (1969); Chem. Abstr., 71 (1969) 92862a. (609) J. R. Hill, U.S. Pat. 2,565,686 (1951); Chem. Abstr., 45 (1951) 9886. (610) L. V. Fodiman, USSR Pat. 77,923 (1949); Chem. Absrr., 47 (1953) 10239. (611) K. Marusza and P. Tomasik, Stuerke, 46 (1994) 13-19. (612) Polymer Corp. Ltd., Belgian Put. 659,260 (1960); Chem. Abstr., 63 (1965) 18432. (613) R. W. Kerr, U.S. Pat. 2,468,207 (1949); Chem. Abstr., 43 (1949) 6850. (614) Oxford Paper Co., French Pat. 1,351,615 (1964) 5892. (615) V. B. Shneerson and A. D. Olesyuk, Tsver. Merul., (9) (1939) 68-70. (616) I. N. Putilova, K. A. Korotchenko, and L. F. Garin, USSR Pat. 161,609 (1964); Chem. Absrr., 61 (1964) 5327. (617) J. Grossfeld, Z. Nuhr. Genussm., 29 (1915) 51-56. (618) I. 1. Alekseeva and 1. 1. Newzer, Zh. Neorg. Khim., 15 (1970) 1244-1247. (619) N. Itoh, Bull. SOC. Sci. Photogr. Jpn., (16) (1966) 24-29. (620) Inveresk Paper Co., British Par. 1,024,881 (1966); Chem. Abstr., 65 (1966) 906. (621) A. T. Czaja, Stuerke, 17 (1965) 211-218. (622) W. A. Samuel, Chemist Analyst, 37 (1948) 33-35. (623) A. M. Beccaria and S. Maneschi, Met. Itul., 56 (1964) 393-398. (624) C. M. Langkammerer, U.S. Pat. 2,489,651 (1949); Chem. Abstr., 44 (1950) 1534. (625) F. K. Signaigo, US. Pat. 2,570,499 (1951); Chem. Absfr., 46 (1952) 3783. (626) C. Muzirnbaranda and P. Tomasik, Stuerke, 46 (1994) 469-474. (627) Farbenfabdken Bayer A.-G., British Pat. 1,111,929 (1968); Chem. Abstr., 75 (1971) 1330311. (628) Zhang Liping, Chen Liying, and Zhang Yishen, Yingyung Xuebuo, 10 (1988) 220-223; Chem. Abstr., 110 (1989) 211355~. (629) E. Undritz and B. Fraenkel, Sungre, 9 (1964) 437-440. (630) S. Suzuki and K. Arai, Denpun Kogyo Gukkuishi, 10 (1962) 33-37; Chem. Abstr., 63 (1965) 10158. (631) Shi Decheng, Shipin Yu Fujiuo Gongye, (2) (1989) 69-70; Chem. Absrr., 111 (1989) 113936~. (632) W. Leszczynski, Acru Aliment. Pol., 11 (1985) 21-33. (633) 0. Durieux, Bull. SOC. Chim. Belg., 27 (1913) 90-97. (634) E. M. Batisse, C. R. Acud., Sci., 230 (1950) 570-572. (635) 1. Iwasaki, Trans. AIME, 232 (1965) 383-387. (636) Z. Synowiecki, Polish Put. 45 026 (1961); Chem. Abstr., 57 (1962) 9966u. (637) A. Krause, M. Belzynska, W. Jagodzinski, and F. Krochmal, Kolloid-Z., 179 (1961) 70-72. (638) A. Krause and M. Rychlewska, Kolloid-Z., 185 (1962) 63. (639) T. Goto and M. Ikeda, Tohoku J. Agr. Rex, 13 (1962) 287-292. (640) A. P. Safronov, N. S. Razumikhina, and A. N. Efremova, Poligrufiyu, (11) (1968) 24-26.

COMPLEXES OF STARCH WITH INORGANIC GUESTS

343

(641) L. J . Klotz, U.S. Pat. 2,968,653 (1961); Chem. Abstr., 55 (1961) 8775. (642) A. Krause, Z. Narurforsch., 15b (1960) 683-684. (643) J. Lechter and M. A. Joslyn, Cereal Chem., 44 (1967) 346-352. (644) S. Suzuki and K. Arai, Denpun Kogyo Kaishi, 10 (1962) 30-33; Chem. Absrr., 63 (1965) 10157. (645) J. Mellanby, Biochem. J., 13 (1919) 28-36. (646) W. Schumann E. Bayer, T. Ito, and Y.Nawata, German Pat. DE3,727,704 (1989); Chem. Absrr., 112 (1990) 756071. (647) E. Bayer, W. Schumann, and K. E. Geckeler, Polym., Sci. Technol. (Plenum), 33 (1986) 115-125. (648) L. A. Gugliemelli, W. M. Doane, C. R. Russell, and C. L. Swanson, J. Polym. Sci., Part B, 10 (1972) 415-421. (649) L. A. Gugliemelli and C. R. Russell, J. Polym. Sci., Part B, 9 (1971) 711-716.

This Page Intentionally Left Blank

.

ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY VOL . 53

COMPLEXES OF STARCH WITH ORGANIC GUESTS* BY PIOTRTOMASIK AND CHRISTOPHER H. SCHILLING Department of Chemistry and Physics. The Hugon Kollataj Academy of Agriculture. 30 059 Cracow. Poland; and Ames Laboratory** and Department of Materials Science and Engineering. Iowa State University. Ames. Iowa 50011

V. Introduction ...................................................... VI . Preparation Methods ............................................... VII . Complexes with Aromas and Flavoring Agents 1. Aliphatic and Aromatic Hydrocarbons .............................. 2. Haloalkanes and Halobenzenes .................................... 3. Nitrogen-Based Compounds 4 . Simple Sulfur-Containing Compounds ............................... 5 . Alcohols 6. Phenols ...................................................... 7. Ethers ....................................................... 8. Aldehydes .................................................... 9. Ketones ...................................................... 10. Carboxylic Acids ............................................... 11. Carboxylic Esters ............................................... 12. Nitriles ....................................................... 13. Amines 14. Carboxyamides ................................................ 15. Vitamins ..................................................... 16. Sulfates and Sulfonates (Surfactants) VIII . Complexes with Dyes .............................................. IX . Complexes with Lipids .............................................. 1. Introduction 2. Native Starch-Lipid Complexes ................................... 3. Preparation Methods ............................................ 4 . Structures and Properties of Complexes 5. Functional Properties of Starch-Lipid Complexes .....................

...........................

...................................... ......................................................

......................................................

................................

...................................................

.............................

346 350 352 352 357 357 359 360 364 365 365 366 367 372 373 373 374 374 375 376 385 385 386 387 392 396

* This is a companion

article to the immediately preceding Chapter “Complexes of Starch with Inorganic Guests. and the numbering of references. figures. tables. and the Table of Contents is consecutive from the prior article . ** Ames Laboratory is operated by Iowa State University under the contract number W7405-eng-82 with the U . S . Department of Energy . ”

345

Copyright 0 19Y8 by Academic Press. All rights of reproduction in any form reserved .

346

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

6. Digestibility of Starch-Lipid Complexes. ............................ 7. Analysis of Lipids in the Presence of Carbohydrates ................... X. Starch Complexes with Mono- and Oligosaccharides ...................... XI. Starch Complexes with Macromolecules 1. Starch-Protein Complexes. ....................................... 2. Complexes with Dextrins, Polysaccharide Gums, Alginates, Pectins, and Starch Derivatives .............................................. 3. Complexes with Cellulose and Modified Cellulose ..................... 4. Complexes with Synthetic Polymers ................................ References ......................................................

................................

399 400 400 405 405

41 1 412 413 414

V. INTRODUCTION Starch in plants is accompanied by water, metal ions, lipids, proteins, sterols (such as saponins), and alkaloids (as in such "exotic" plants as Dia~coracea).'~~ Several of these components can be washed out by the isolation of starch, some of them are extractable with organic solvents, and some are volatized by steam treatment. With the exception of metal ions (preceding article, p. 263), the foregoing components form physical mixtures with starch and do not chemically bond with either amylose or amylopectin. Therefore, one may assume that amylose and amylopectin form inclusion complexes with organic components that are similar to those mentioned in the preceding article. Bear4' and R ~ n d l e ~ observed '.~~ that starch of the A and B patterns transforms into V-type starch in contact with 1-butanol (namely, to a form capable of producing a blue color with iodine in KI). In this case, the randomly coiled amylose component is transformed into a helical structure. The hydrophobic carbon chain of 1-butanol, acted upon by its van der Waals forces as a complexing agent, causes a specific spatial orientation of the glucose residues in amylose. This orientation generates a helix having a hydrophobic cavity that includes a molecule of 1-butanol. A similar effect, forming either a helix or an extended coil, can be achieved by several other organic compounds and by alkali species.'85 Studies by Brant efu1.650-652indicate that only a small amount of complexing agent is required to form the helical structure of arnylose. On the other hand, attempts to form complexes with amorphous amylose have not been su~cessful."~~ Therefore, it may be readily deduced that complexes of organic compounds involve inclusion inside the helix rather than surface sorption. At first glance it may be assumed that the presence of an organic compound having a relatively long carbon chain is necessary for the coiling of amylose to trap organic molecules inside the coil. This could, for example, explain the observation of KodaU9 that ethane, ethyne, and chloromethane sorbed on starch less readily than did inorganic gases (CO, COz,NO, H2S, and SO?).

COMPLEXES OF STARCH WITH ORGANIC GUESTS

341

The carbon chains of these compounds were too short and, as a consequence, the sum of the van der Waals forces was too low to cause coiling. Another condition for the formation of the complex is the geometry of the guest molecule. For example, the size of the helix interior must be such that the guest molecule fits inside the helix. Several experiments have shown that the diameter of the helix cavity is variable and can expand from 4.5 to 6.0 This diameter also depends on the number of turns of the Thus, the helix has a variable inclusion capacity and it can hold even seemingly bulky guest molecules. The concept of a long enough hydrophobic portion of an organic component as a necessary condition for the complexation is only partly correct. Kuge and take^^^^ (Fig. 42) observed that a group of alcohols, ketones, and alkyl halides (among them such bulky compounds as cyclohexanol and cyclohexanone) are much better sorbed on amylose (area 1) than such compounds as benzene, toluene, branched alkyl halides, carbon tetrachloride, tert-butanol, isomeric xylenes, and P-pinene (area 2). Also, as shown in Fig. 42, linear, branched, and cyclic alkanes, such as n-hexane, isopentene, and cyclopentane, are sorbed in very small amounts (area 3). The polar group terminating each alkyl chain is also an important factor. The borderline between those three groups in Fig. 42 proceeds neither along the nature of the polar group nor along the steric properties of the hydrophobic moiety. In the case of monosubstituted benzenes, the inclusion capacity increases with increasing dipole moment and boiling point of the potential guest. Esters of benzoic acids form complexes less readily as the chain length of

A.

Amylose in column,o/o

FIG.42.-Relationship between retention volume and amylose content in colum11.6~~ (See text for explanation of areas 1 , 2, and 3.)

348

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

the esterifying alcohol exceeds 10 carbon atoms."' The curved shape of the relationship shown in Fig. 42 suggests that there are two types of sorption on amylose: (1) inclusion inside the helix, and (2) surface sorption."' The formation of surface-sorption complexes can explain why several dyes, which are usually rather large molecules, form complexes with starch. The branches of amylopectin can also undergo coiling, which in turn can be involved in complexation. French et ~ 2 1 . ~ confirmed ~' that amylopectin exhibits a weak tendency for complexation of certain organic compounds (see Table XXII) where the complexation ability is expressed by means of the iodine-binding capacity and p12 (namely, the negative logarithm of the apparent iodine concentration at half of its maximum potential binding capacity). Obviously, the complexing ability of starch depends on the variety of starch and hence the amylose-to-amylopectin ratio. Osman-Ismail and S01ms~~' investigated the formation of inclusion complexes of 1-hexanol, 1-octanol, 1-decanol, decanal, 1-menthol, 1-menthone, limonene, and 0pinene with rice, corn, and potato starch, and also potato amylose. The ability to form inclusion complexes with these materials is as follows: potato starch > rice starch > corn starch > potato amylose, a trend which has no relation to the content of amylose in these starch varieties. It should be emphasized that this order varies according to the nature of the guest molecule. For example, the relative percentages of acetone inclusion are as follows: potato (4.15) > cassava (3.40) > wheat (3.30) > maize (2.65); for methanol the corresponding order is potato (1.90) > cassava (1.30) > wheat (1.20) > maize (1.15).659 Inclusion complexes are commonly characterized either by the temperature of their formation"' or by the binding parameters of different ligands. These parameters originate from the Scatchard equation?'

r = n k cf/(l + k q ) ,

(11)

TABLE XXII Properties of Complexed Amylose and Amylope~tin~~'

Iodine-Binding Capacity Guest Molecule

Amylose

Amylopectin

Beta-Amylase Limit (Amylose)

Benzene Carbon tetrachloride Chloroform Cyclohexane 1,2-Dichloroethane 1-Pentanol 1.1,22-Tetrachloroethane

18.0 16.7 14.0 14.7 17.9 16.1 16.5

0.3 0.0 0.0 0.0

68.8 69.5 68.8 68.0 (-0.2) 67.5 67.0

-

0.3 0.0

COMPLEXES OF STARCH WITH ORGANIC GUESTS

349

where r is the average number of moles of bound ligand per mole of glucose unit of starch, n is the maximum number of moles of bound ligand per mole of glucose unit of starch, k is the intrinsic binding constant (an association constant), and cf is the molar concentration of unbound ligands at equilibrium. As just mentioned, starch and its components can adsorb by two mechanisms: inclusion or surface sorption. A two-parameter equation which accounts for these two mechanisms appears to be more appropriate: r

=

n1 kl cf/(l + kl cf) + n2 k2 cf/(l + n2 k2).

(14

In this expression, the subscripts 1 and 2 refer to inclusion and surface sorption, respectively. Other techniques for characterizing complexes include desorption methods, elemental analysis, X-ray diffraction, spectroscopic methods, thermogravimetry, and others. Since native complexes of starch, especially those with lipids and proteins, are known, it may be assumed that the evacuation of guest molecules can provide space for other guest molecules such as aromas, waxes, and various biologically active compounds (pesticides, pharmaceuticals, and so on). Such evacuation of natively residing guest molecules usually results in collapse of the helix. It is also known that the coiling and decoiling of amylose and certain branches of amylopectin is normally reversible. It may also be assumed that replacement of one guest molecule by another without the decoiling-coiling step should also be taken into account. Several observations suggest that wet starch (that is at least randomly coiled) accepts some organic molecules (such as alcohols) more readily than does dry starch (that is, more amorphous). In order to form a complex with methanol, a dry starch has to be used, whereas complexes with ethanol, 1-propanol, and benzyl alcohol are formed more readily with a native starch (that is, with a starch-water complex).661*662 Water in starch not only provides coiling favorable for the entry of guest molecules, but swelling also provides guest molecules access to the interior of granules. In addition, successive sorption and desorption of guest molecules from starch can affect the structure of granules.663Inclusion complexes may also form that involve inclusion of a second guest molecule into a preexisting inclusion complex. For example, starch containing 0.5%of included CaC12 adsorbs malt alpha-amylase,6@and starch-ZnCI2 complexes adsorb triethanolamine.665This is not always the case because, for instance, some bi- and trivalent cations inhibit inclusion of albumin and globulin into starch.666 There are several practical aspects to the formation of inclusion complexes. One of the earliest applications is the flocculation of starch from aqueous solutions. Among other compounds, the lower alcohols (Cl-C4) and acetone are superior in this respect.667The stabilization of flavoring and aromatizing compounds constitute the most common practical application of inclusion complexation. In this manner, oxidizable food components may be pro-

350

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

t e ~ t e d .Some ~ ~ ,biologically ~~~ active compounds can be introduced into plant and animal organisms in the form of starch complexes.670Stabilization of nitroglycerol in alkali starch has been patented.671Water-dispersible comhave also positions that are inclusion complexes of gossypol and been patented. The selectivity of various organic compounds in the complexation with components of starch can be utilized in fractionation of starch. Kuge and take^^^^ proposed (-)-menthone for this purpose. Other applications of complexation and complexes will be discussed next.

VI. PREPARATION METHODS There are three primary methods of complexation: (1) sorption from the gas phase, (2) sorption from a liquid phase, and (3) blending. Sorption from the gas phase is possible when the guest molecules can evaporate and form a saturated vapor. In this method, starch is placed in a chamber filled with vapor and left until sorption equilibrium is reached. Depending on the character of the guest molecule, equilibrium is reached after a time period which ranges from a few hours to several days. Figure 43 shows that equilibrium with n-hexane and ethyl acetate is reached within 1-2 days, whereas equilibrium with 1-butylamine and ethanol was still not reached even after 60 and 75 days, respectively.674The shapes of the curves in Fig. 43 suggest the possibility of a side effect, such as swelling. The extent to which guest molecules are complexed is related to their polarity; however, the kinetics of the process do not follow this trend (see also Table XXIII). Sorption of guest molecules from the liquid phase may proceed either when the guest molecules form a liquid phase by themselves, or when they are dissolved in a suitable solvent (such as water, alcohol, or Me2SO). In the latter case, the kinetics of complexation can be monitored by spontaneous precipitation of the complex. Acceptable results are achieved when the

0

25

50

75

T i m e , days

FIG.43.--Kinetic curves of sorption of volatile aromas on dry starch. (Reprinted with permission from H. G. Maier and A. Bauer, Sraerke, 24 (1972) 101-107.)

COMPLEXES OF STARCH WITH ORGANIC GUESTS

351

TABLE XXIII Content of Flavoring Agents in Air-Dried Starch Films674

Maximum of Sorption Flavoring Agent

After 3 Days, mg/g

Amount, mg/g

Acetic acid Acetone Acrolein I-Butylamine 2-Butylamine tert-Butylamine Die thylamine Ethanol Ethyl acetate Hexanal trans-2-Hexanal 3-Pentanone Propanal Propanoic acid 2-Propanol Pyrazine Pvridine

31 34 10

41 43 25 31

21 21 20 0.2

92 92 19 10 17 8 11 50 31 55 106 146

2 1 5 68 71 24 41 62 74 26 7 44

101

12 4 0 0 7 17 27 0 76 123

reaction mixture is autoclaved. Usually a 1-10% suspension of starch is used for c o m p l e x a t i ~ n . ~ Comparative ~ ~ ~ ~ ~ ' studies revealed that shaking at room temperature produces very similar results, regardless of the starch concentration.65' A conventional procedure for preparing the starchbenzaldehyde complex using alcohols as benzaldehyde-carrying solvents is presented in ref. 661 (see Scheme 1).There is also evidence that moisture in starch significantly improves the extent of inclusion from solutions of higher alcohols, although complex formation can be very slow. For instance, it was reported that a 1%solution of starch binds sorbic acid immediately, whereas a 0.1% solution binds only 1.76% of sorbic acid immediately and a further 44.38%binds after 4 weeks.675 In some instances the carrier of the guest plays the role of emulsifier. For example, alcohols and lower fatty acids or their esters are used in the formation of fat-starch complexes.676In this case, conditions for preparation of complexes resemble conditions for extraction, and unexpected results can accompany both processes. For example, it has been shown that extraction of lipids with 1-propanol from their surface complex with oat starch produced a helical lipid-starch complex that was absent prior to extraction.677 Preparation of complexes by blending entails mechanical grinding of starch and guest molecules (or a source containing the guest molecule) in

352

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING Starch ( 5 g dry basis)

.1 Drying at 100°C in vacuum (omitted in modified procedures) 1 + The solution of guest compound in a carrier-solvent (10 mL) .1 Standing overnight in a stoppered flask

.1 Drying at 40°C

1 Continuous extraction with In-hexane

1 Drying at 100°C in vacuum

.1 Product SCHEME1.-Conventional Process for Preparation of Starch Complexesbh'

a mortar. The resulting mixture is stored in a stoppered flask and then washed several times with a solvent such as ether or Me2S0. In every instance, repeated grinding increases the amount of inclusion c ~ m p l e x . " ~ VII. COMPLEXES WITH AROMAS AND FLAVORING AGENTS Starch complexes with aromas and flavoring agents are usually synthetic in origin. In nature, starch sometimes includes some aroma- and flavorgenic components that generate flavor and aroma on processing (see, for instance, ref. 678). Such agents include mainly aldehydes, ketones, and carboxylic esters; however, hydrocarbons, alcohols, carboxylic acids, and haloalkanes have also been used.

1. Aliphatic and Aromatic Hydrocarbons Published literature on starch complexes with aliphatic and aromatic guest molecules is scarce, and only limited generalizations can be made. For example, it may be observed from Fig. 42 that alkanes and cycloalkanes exhibit two distinct types of sorption behavior: (1) n-Hexane, isopentane, isoheptane, cyclopentane, cyclohexane, and methylcyclohexane are sparingly sorbed (they fall along line 3) whereas (2) isooctane and @-pineneare sorbed in larger amounts (in area2 of Fig. 42). Figure43 suggests that the equilibrium sorption occurs rapidly. For example, within the first 60 min, half of the equilibrium amount of n-hexane (6 mg/g of starch) is sorbed from the gas phase. This sorption is evidently strong, since n-hexane cannot be d e ~ o r b e d "at ~ temperatures as high as 80°C. In contrast, both @-pineneand isooctane, being more bulky compounds, are more readily sorbed. The curvature shown in Fig. 42 suggests that there are at least two mechanisms of sorption: (1) sorption

COMPLEXES OF STARCH WITH ORGANIC GUESTS

353

within the helix, and (2) sorption either in the capillaries or on the surface. The observation by KodaM9on the weak sorption of ethene and ethyne on starch, together with the conclusionsdrawn from Fig. 42, suggest that the size of hydrocarbon is a critical factor controlling sorption kinetics. Only P-pinene and isooctane have a size that fits the cavity of the helix. X-Ray diffraction analysis of an insoluble potato ?tarch-P-pinene complex revealed the following interplanar spacings (in A): 12.80 (strong), 7.70 (medium), and 4.83 (strong) (see Table XXIV). The Scatchard parameters are as follows: kl = 1.30 x lo1,k2 = 1.81, nl = 0.027, and n2 = 0.089 (Table XXV).656These data suggest, especially in comparison with data for other compounds mentioned in Table XXV, that sorption is weak and proceeds in two distinct regimes. The concentration of limonene in starch is linear679 against k. Reported temperatures of the formation of various complexes are shown in Table XXVI. The yields of complex formation (on the basis of dry weight of starch) are 17.2%for starch-cyclohexane, 20.4% for starchlimonene, and 9.2% for starch-P-pinene complexes.673Complexes of starch with petroleum ether (5.4-5.7%) are also known.681*682 Less information exists on the sorption behavior of aromatic hydrocarbons such as benzene, toluene, the three isomeric xylenes, mesitylene, and TABLEXXIV X-Ray Diffraction Patterns of Potato Starch and Some of Its Complexes6” Guest Molecule None

(-)-Menthol

(-)-Menthone

Decanoic acid Linoleic acid

Spacing, A

Intensity

15.8 8.90 7.94 6.14 5.16 4.54 4.00 3.70 3.38 2.60 12.75 7.60 4.90 12.75 7.60 4.90 11.70 6.75 12.70 6.80 4.80 4.40

m vw vw m s

Guest Molecule 1-Hexanol

1-Octanol

W

m m

1-Decanol

W W

s s s

Decanal

P-Pinene

S S

S

m s m m m m

Oleic acid

Octadecanoic acid

Spacing, A

Intensity

11.65 6.60 4.80 11.70 6.75 4.42 11.70 6.70 4.41 11.70 6.80 4.42 12.80 7.10 4.83 11.50 6.90 4.38 12.90 7.90 4.37

s s s S

s s s s s

m s

m s

m s m m m s S

s

354

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

TABLE XXV Scatchard Parameters of Different Ligands with Potato Starch at pH 7.06%

1-Hexanol 1-Octanol 1-Decanal Decanal Decanoic acid Octadecanoic acid Oleic acid Linoleic acid (-)-Menthone (-)-Menthol P-Pinene

54.5" 219 125 125 330 357" 666 959 184 143" 13.0

0.10 0.05 0.04 0.01 0.07 0.069 0.019

0.004 0.012 0.007 0.027

21.5 12.9

-

43.5

-

57.7 46.4 8.97 -

1.81

0.11 0.1 1 -

0.19 0.089 0.020 0.045 -

0.089

" k , is the total constant because the Scatchard plot is linear in its whole range.

p-cymene. Data for these hydrocarbons resides in area 2 of Fig. 42, along with P-pinene and i s ~ o c t a n e . ~The ' ~ temperatures of complex formation are reported in Table XXVI. Yields of complexation are 23.4, 22.9, and 18.2%,respectively.673It is apparent that they are higher than the complexation yields of alkanes and alkenes. The equilibrium sorption of benzene on both amylose and amylopectin is reached within 14 days. After this time period, 3 mg of benzene is sorbed per gram of amylose, and 4 mg of benzene per gram of a m y l ~ p e c t i nThe . ~ ~characteristics ~ of gelation of potato starch change dramatically after 3 h of refluxing in benzene; however, these changes are much smaller when starch is heated for 3 h in toluene at 100 "C. The dramatic changes observed with benzene are interpreted as resulting from the collapse of the helix on azeotropic evacuation of water. Observations of starch granules by optical microscopy over the temperature range of 60-245 "C confirm major changes in the appearance of granules after refluxing in benzene. Some differences in appearance are also evident in the case of air- and oven-dried potato starch. Analysis of the dry mass content shows that 12-13% of benzene remained in starch after such heat treatment; however, thermogravimetric analysis did not reveal any evidence of benzene being desorbed before decomposition of the s t a r ~ h . ~Ben~',~~~ zene can displace acetone, diethyl ether, or methanol from their inclusion complexes. Such replacement of one ligand by another is incomplete. The origin of starch plays a role in this repla~ement.6~~@~*~'*

COMPLEXES OF STARCH WITH ORGANIC GUESTS

355

TABLEXXVI Starch Inclusion C o m p I e ~ e s ~ ~ - ~ ~ ~ ~ Guest Molecule Hydrocarbons Benzene Bicyclo[l,2,2]heptene Cycloheptadiene Cycloheptane Cycloheptene Cyclohexane Cyclohexene Cyclooctane Cyclopentane p-Cymene 23-Dimethylbutane Limonene Methylcyclohexane Methylcyclopentane P-Pinene o-Xylene Halohydrocarbons Bromocyclopentane o-Bromotoluene Carbon tetrachloride Chloroform 2,3-Dibromobutane 1.2-Dichloroethane 1.2-Dichloropropane Fluorobenzene Hexachloroethane 1,1,2,2-Tetrabromoethane 1,1,2,2-TetrachIoroethane 1 ,l,l-Trichloroethane 1,1,2-Trichloroethane AIcohoIs Borneo1 I-Butanol fert-Butanol” Citronellol 1-Decanol Ethanolh Geraniol 1-Hexanol 4-Hydroxy-4-methyl-2-pentanoneh Linalool (-)-Menthol Methanol”

Temperature of Formation, “C

Yield’

56 70 57 81 61 67-69 65 53 41 49 26 25 41 40 23 30-32

23.4

53 32 66 52 27 50 53 52 78 69 83 57 50

17.2

22.9 20.4

9.2 18.2

18.2 20.0

26.1

67 46

25.7 26.6

62 37

25.5

45 42

25.5

65 66

22.8 26.4 (continues)

356

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING TABLE XXVI (Continued) Guest Molecule

1-Octanol 1-Pentanol Perillyl alcohol Pinacol Phenols p-Cresol 2,4-Dinitrophenol 1-Naphthol 2-Naphthol Phenol Aldehydes Decanal Octanal Perillaldehyde Ketones Acetoneh Camphor Carvone Cyclohexanone Dirnedone 2,6-Dimethyl-4-hexanone (-)-Menthone 4-Methyl-2-butanone Pinacolone Carboxylic acids 2-Bromopropanoic acid Butanoic acid Decanoic acid Dodecanoic acid Hexanoic acid Linoleic acid Octadecanoic acid Octanoic acid Oleic acid Tetradecanoic acid Miscellaneous Diethyl malonate Nitrobenzene Pyridine" Quinoline

Temperature of Formation, OC

Yield"

40 45 62 55

24.6 28.8

72 60 85 55 61

32.2 22.6 31.5 16.1 24.2

36 36 70

25.5

60 52 85 80 23 55 86 54 53

21.8 8.9 15.0 22.9 1Y.7 13.0 24.5 20.5 31.0

44 50 46 40 50-55 64 35 50 21

18.4

21.8 21.2 21.1

40

23 61

2.7

85

24.1

If available. The efficiency is dependent on the concentration of the guest molecule.

COMPLEXES OF STARCH WITH ORGANIC GUESTS

357

2. Haloalkanes and Halobenzenes Sorption data for haloalkanes are spread widely among all regions in Fig. 42. There seems to be no simple and logical relation between these positions and the dipole moments, boiling points, and size and shape of the guest molecules. Similarly, the temperatures of complex f o r m a t i ~ n ~ ~ ~ @ ~ are not amenable to simple interpretation. The sorption of alkyl halides is possible by replacing diethyl ether:59,681.682,pyridine,659*681,682 or dimethyl sulfoxide6" from their complexes with starch or amylose. In case of carbon tetrachloride, its sorption capacity is between 3.0 and 4.9%.The conversion of the pyridine complex is more complete, perhaps because of the known swelling effect of pyridine on starch (see later discussion). The low sorption capacity for C C 4 has been confirmed by Gupta and Bathia.3s4 These authors also observed good reproducibility of C C 4 adsorptiondesorption isotherms in successive experiments. The sorption-desorption isotherm of C C 4 on wheat flour proceeded without any hysteresis.6%The gelation characteristics of potato starch are only slightly affected by conditioning in chloroform (Table XXVII), but the appearance of the granules changes substantially (Table XXVIII).6x9 3. Nitrogen-Based Compounds

Whistler and Hilbert687observed that nitroalkanes form complexes with starch, a fact utilized from fractionating starch into amylose and amylopectin. The authors indicated that amylose forms complexes, whereas amyloTABLE XXVII Characteristics of Gelation of Air-Dried Potato Starch after Conditioning in Various Organic Solvents684

Solvent None Acetone Acetonitrile Benzene Chloroform N,N-Dimethylformamide Ethanol Nitrobenzene I-Propanol Pyridine Toluene "

Temperature Viscosities, mP-see Temperature of of Max. Gelation, "C Viscosity, "C Maximum At 96°C" At 50°C 63.5 62.5 67 62 62.5 74 63 63 62.5 83.5 63

73.5 73 79 71.5 72 95 75 76 76 96 72.5

4347 2724 369 3594 3764 263 2693 60 3152 397 2753

Values in parentheses represent viscosity maxima after 1200 seconds.

63 (322) 54 (178) 85 (73) 6 (76) 236 (263) 203 (138) 39 (393) 66 (130) 48 (337) 397 (163) 94 (241)

4194 2111 1999 6 1040 1184 2210 1279 4621 938 1939

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

358

TABLE XXVIII Microscopic Observations of Air-Dried Potato Starch aPter Conditioning in Organic SoIvents6&l Solvent None

Benzene

Conditions (Temp. "C)

Observation with Normal Light

Observation with Polarized Light

60

yellow points, dashes, crosses

yellow points, dashes, blue spots no change no change yellow crosses, edges of grains illuminated pale-blue spots (235°C) yellow crosses. pale blue spots yelow points, dashes and crosses no change no change yellow points and spots blue points and spots (180°C) yellow points and dashes, blue spots yellow dashes, pale blue spots no change no change yellow dashes and crosses shining ceases (230°C)

60 to 245 245 60 60 to 245 245

Toluene

Nitrobenzene

Pyridine

Chloroform

Acetonitrile

60 to 245 245 60 60 to 245 245

yellow points, dashes, and crosses no change no change yellow points and spots no change no change

60

yellow dashes, blue spots

60 to 245 245 60 60 to 245

no change no change yellow dashes and crosses grains melt, shining ceases dashes, crosses no change yellow dashes, crosses blue spots points turn into dashes

60

245 60 60 to 245 245

Ethanol

1-Propanol

DMF

no change no change yellow, dashes, blue points spots no change no change

60 60 to 245 245 60 60 to 245 245

60 60 to 245

245

no change yellow dashes, crosses blue spots yellow dashes and points blue spots yellow points and dashes yellow points and dashes blue spots blue spots yellow points, blue spots yellow dashes and crosses pale spots and dashes (185°C) points turn (130°C) yellow points and dashes yellow points and dashes yellow dashes, blue spots yellow dashes, blue spots points turn (130°C) points turn (130°C) yellow points, dashes edges of grains illuminated blue spots, yellow dashes yellow spots yellow dashes, pale spots yellow dashes yellow dashes (190'C) yellow dashes, blue spots (190°C) no change no change

COMPLEXES OF STARCH WITH ORGANIC GUESTS

359

TABLE XXVIII (Continued) Solvent Acetone

Conditions (Temp. "C) 60 60 to 245

245 Nitromethane

60 60 to 245 245

Observation with Normal Light yellow dashes no change no change yellow dashes, blue spots no change no change

Observation with Polarized Light illuminated yellow dashes, blue spots shining ceases (225°C) yellow dashes yellow dashes, blue spots no change yellow spots and dashes pale blue spots

pectin does not. The X-ray diffraction pattern of amylose complexes is essentially the same, regardless of which nitroalkane (nitromethane, nitroethane, l-nitropropane) is used. Such complexes readily retrograde. The effect of nitromethane on the gelation characteristics of potato starch, as well as on the appearance of the gran~les,6'~*~'~ was interpreted in terms of the low acidity of nitromethane (aci-form) as well as a possibility of the Henry6" reaction. Because of the sensitivity of the gelation characteristics to subtle structural changes, even traces of this reaction could affect the characteristics. There is little published information on starch complexes with nibrobenzene. Complexes have been reported, but their properties were not detailed.673@0Kuge and take^^^' reported that formation of the complex requires alkaline solutions. Ulmann and S ~ h i e r b a u m ~reported ' ~ . ~ ~ ~formation of the complex from a potato starch-acetone complex via a starchpetroleum ether complex boiled under reflux. The resulting complex contains 5.6-5.9% of the guest nitro molecule. Because of the possible oxidation of starch by nitrobenzene, the characteristics of gelation and the appearance of starch granules are strongly influenced by this n i t r ~ a l k a n e . ~ ~ ~ ~

4. Simple Sulfur-Containing Compounds The effects of sulfonic acids on starch are discussed later (p. 375). Dimethyl sulfoxide and carbon disulfide are the only other sulfur-containing compounds that have been examined with respect to their complex formation with starch. For example, a complex of potato starch with carbon disulfide was prepared via the starch-acetone complex on refluxing. It was reported that this complex contains 5.8-5.9% of CS2.682Dimethyl sulfoxide causes expanded coiling of amylose without the formation of a Banks and Greenw~od"~reviewed the Mark-Houwink exponent for Me2SO-starch solutions. Reported variations in this exponent are believed

360

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

to be caused by the reaction of Me2S0with starch.h8yErlander and Tobid'" observed that the helices of amylose and amylopectin are stabilized by either the dihydrate or anhydrous Me2S0. In acidic media, the stability increases, perhaps because of the formation of the protonated form of Me2S0 (Me2S+OH-).A complex of amylose with Me2S0 is also reported for the synthesis of amylose-alcohol and amylose-haloalkane c~mplexes."~ 5. Alcohols

Several reports discuss inclusion complexes of starch and its components with alcohols. In Fig. 42, all tested alcohols, with the exception of tertbutanol, follow line 1. This suggests that the size of the hydrophobic moiety of alcohols is a key factor.6s4The complexation yield of lower alcohols depends on the starch-to-alcohol ratio.h73The number of turns of the helix in the complex also depends on the complexed Previous reports on starch-alcohol interactions assumed that only physical sorption is involved, despite observations of the irreproducibility of successive adsorption-desorption isotherms for starch-methanol and starch-ethanol systems. This irreproducibility was assumed to be the result of swelling.354 Several years later Poliszko et aLh91studied the sorption of methanol on starch gels and confirmed that successive sorption-desorptions open new specific centers of sorption. Based on a comparison of the results of adsorption (entropying) of water and both of the aforementioned alcohols, a relationship between the volume of sorbate molecule and the entropying effect was suggested. Russian scientists studied the competitive sorption of water and alcohols by starch from water-alcohol solutions. For example, Chapek6y2observed that, in contrast to water, ethanol does not condense in capillaries. The amount of sorbed water was observed to decrease with increasing alcohol concentration in the solution. In contrast, the amount of sorbed alcohol first increases and then decreases with increasing water concentration.hh2It was also observed that water can be selectively adsorbed from water-ethanol solutions by minimizing the amylopectin-to-amylose ratio in starch. Water sorption by corn grits is usually decreased by grindingPY3Heats of sorption of starch with ethanol were determined by Dumanand Rebar et aL417The heat of sorption depend on the skii et al.6y4.6y5 concentration of water in starch as well as the concentration of the aqueous solution of alcohol (see Fig. 44). In contrast to water adsorption, the adsorption of ethanol is rather independent of the variety of ~ t a r c h . 4Like ~ ~ certain other molecules, ethanol has the effect of crystallizing starch and its component~,6~~ an effect that is not linearly proportional to concentration. The intrinsic viscosity of aqueous

COMPLEXES OF STARCH WITH ORGANIC GUESTS

361

FIG.44.-Relationship between heat, Q, of treating starch with water, ethanol, and mixtures thereof!y4

amylose solutions reaches a maximum at 12% ethanol and then displays a minimum at 16% ethanol. The authors6y7interpreted this phenomenon as a result of the aggregation of amylose, which increases its total length. On the other hand, Weige1698determined 30-35% of ethanol as the optimal concentration for starch crystallization. The effects of processing potato starch in ethanol and I-propanol on the gelation characteristics are similar, but the effect of this treatment on the appearance of starch granules in normal and polarized light is different (see Tables XXVII and XXVIII). The discovery of the V-type, helical amylose (see p. 265) that forms when amylose interacts with 1-butanol was crucial for the development of the chemistry of starch inclusion complexes. It soon appeared that 1-butanol complexes solely with the amylose component. This selectivity became the first convenient method of fractionating starch. This method was first described by S ~ h o c and h ~ ~later ~ developed by Kerr et uL700-7"2 and othe r ~ . ~ " , ~An " ~ improved procedure was subsequently ~atented.7"~ The amount of 1-butanol adsorbed in amylose is increased by the presence of moisture and is also dependent on two key factors: the time of contact with that alcohol and the origin of the amylose, as shown in Table XXIX.

TABLE XXIX Absorption of Butanol Vapor by Solid Amylose of Various Moisture content^'^ Absorption (YO)at Time (Days)

Amylose Origin Corn Tapioca Retrograded Amorphous

Moisture Content, 2 5-6 2 5-6 2 5-6 2 5-6

O/O

1

6

18

4.44 5.62 3.74 5.74 0.34 0.20 0.41 0.20

5.99 12.49 6.56 13.50 0 0.20 0 0.20

12.95 8.84 13.85 0 0.20 0 0.30

u)

25

27

32

39

18.2

9.02 21.4 10.39

7.86 21.4 9.44

9.23

7.90

16.0 9.23 18.1

18.2 0

0.2

0

0

0

0.2 0

0.25

0

0.35

41

62

18.1

17.4

0.2

0.4

0.30

0.25

COMPLEXES OF STARCH WITH ORGANIC GUESTS

363

Starch fractionation using l-pentan01,6~~~”~ cyclohexanol,7m2-butanol, and 2-propano16” instead of 1-butanol have also been proposed. Amylose complexes with all of the normal-chain alcohols have essentially the same X-ray diffraction pattern, which differs from the patterns of amylose complexes with branched a l ~ o h o l s . ~ ” ~ . ~ ~ ~ According to Hollo et ~ l . , ~the ” ’ low stability of starch-alcohol Complexes (lower than that of the starch-iodine complex) is caused by the relatively small amount of space inside the amylose helix that is available for the hydrophobic moiety of the alcohol. The data in Table XXX appear to confirm this assumption and indicate iodine sorption amounts by starch complexes with subsequent members of the homologous series of alcohols. With the exception of tert-butanol, the iodine uptake decreases as the alcohol inside of the helix becomes more bulky. Conditions for the formation of potato starch-alcohol complexes do not follow predictable trends. For example, all complexes are formed more readily from air-dried starch rather than from oven-dried starch. Only the starch-methanol complex favors room temperature for its formation; the other alcohols require elevated temperatures for effective complexations (see Table XXXI).65y~681~6x2 In contrast, moisture inhibits the formation of the starch-( -)-menthol complex, which is characterized as an interchain complex.710The Scatchard binding parameters show that (-)-menthol and 1-hexanol adsorb on starch by only one mode, whereas 1-octanol and 1decanol adsorb in two modes.656The results for the latter two alcohols indicate that the helices are not fully filled before the second mode of complexation starts. Temperatures of the formation of starch-alcohol complexes likewise do not follow any clear r e l a t i o n ~ h i p . 6 Bushuk ~ ~ * ~ ~ and reported that the amount of guest molecules (H20, MeOH,

TABLE XXX Effect of Various Alcohols on the Iodine Uptake, O/O, by S t a r ~ h ’ ~ Alcohol, V% Methanol Ethanol 1-Propano1 2-Propanol 1-Butanol 2-Butanol terr-Butyl alcohol 1-Pentanol 2-Pentanol Cyclohexanol

O.Oo0

0.415

0.830

1.679

3.340

8.350

4.22 4.22 4.22 4.22 4.22 4.22 4.22 4.22 4.22 4.22

-

4.17 4.09 3.97 4.10 3.92 4.08 4.12 3.80 3.95 3.51

4.07 3.98 3.76 3.99 3.65 3.76 3.91 3.46 3.69 2.85

3.95 3.72 3.50 3.80 3.38 3.57 3.74 3.14 3.46 2.07

3.87 3.50 3.08 3.57 2.85 3.24 3.49 2.51 3.04 0.85

-

4.14 4.10 4.08 4.08 3.99 -

3.82

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

364

TABLE XXXI Sorption of Alcohols by Starch Depending on the Reaction Conditionsm' Room Temperature

Reflux

Alcohol

Air-Dried

Vacuum-Dried

Air-Dried

Vacuum-Dried

Methanol Ethanol 1-Propanol 2-Propanol 1-Butanol 2-Butanol 2-Pentanol

1.1-1.6 2.4-3.3 0.5-1.1 0.1-0.9 0.1-0.5 0.1-0.5 0.2-0.7

0.3-0.9 0.1-0.7 0.1-0.2 0.1-0.4 0.4-1.6 0.4-1.6 0.6-1.1

0.6-2.0 3.3-3.6 4.5-4.8 3.6-4.3 3.9-4.6 4.0-5.0 1.6-2.2

0.9-2.3 1.4-2.4 0.3-0.8 0.3-0.9 0.7-1.4 0.4-0.9 0.5-1.2

EtOH, CClJ included in wheat flour decreases with the molar volume and increases with the dipole moment of these guests. The complex of 3,4-dinitrobenzyl alcohol with starch was prepared as a local radiation sensitizer in tumor radi~therapy.~~' Sorption of 2-phenoxyand 2-(ch1orophenoxy)-ethanol on starch was also studied by M ~ C a r t h y , ~ ' ~ who observed starch to be a suitable complexing agent. It was assurned7l3that other naturally occuring alcohols-sterols-form complexes with starch. Thus, complexes of cholest-5-ene-3P-01 (cholesterol), cholest-5-ene(24R)-24-methyl-3~-ol (campesterol), stigmast-5,Z,22diene-3/3-01 (stigmasterol), and stigmast-5-ene-3P-01 (sitosterol) were prepared by blending the sterols with a 0.2% solution of rice starch. Independent of the concentration of sterols, 33, 25, 22, and 20% of these sterols were complexed, respectively. Hydrolysis by cold acid led to recovery of approximately 20% of the sterols. Treatment with pyrogallol was completely ineffective, as less than 1% of the guest molecules could be liberated. Hydrolysis with beta amylase liberated 38-75% of complexed sterols. A starch-cholesterol complex was also studied by P01lak.~'~ 6. Phenols

Phenols readily form starch complexes, and they are also readily extractable. As indicated in Table XXXII, the extraction of phenols from their complexes with amylopectin and amylose using diethyl ether generally proceeds more readily with amylopectin. Relationships between the structure and stability of phenol-starch complexes are not clearly understood. Apart from the complexes of phenols listed in Table XXXII, complexes of chlorocresols,712three isomeric nitrophenols,715resorcinol, phloroglucinol, and rutin,'16 have been reported. The formation of complexes with nitrophenols has been monitored by ultraviolet

COMPLEXES OF STARCH WITH ORGANIC GUESTS

365

TABLE XXXII Diethyl Ether Extraction of Phenols fkom Amylose and Amyl~pectin~'~

Amount of Extracted Phenol, YO" Amylose

Amylopectin

Phenol

After 7 Weeks

After 1 Year

After 7 Weeks

After 1 Year

Phenol Guaiacol Vanillin Thymol

8 24 100 97

17 (42) 0 (11) 93 (7) 43 (35)

17 53 81 95

5 27 51 95

"The figures in parentheses relate to extraction with moist diethyl ether. The other extractions were performed with dry diethyl ether.

spectroscopy. In general, phenols require relatively high temperatures for the formation of c o r n p l e ~ e s . ~ ~ ~ ~ ~ ~ ~ Starch complexation with thymol was proposed for the fractionation of starch,704but the procedure is not as efficient as that with 1-butanol. Fractionation with thymol followed by the use of 1-butanol is used to produce high-purity components. Complexation with naphthols revealed that 1-naphthol forms complexes with starch more readily than does its 2isomer.6731-Naphthol complexes in two modes, as suggested by the Scatchard plot, and the binding is rather weak.717Complexes between a formaldehyde-hydroquinone polymer and starch have also been d e t e ~ t e d . ~ "

7. Ethers Ulmann and S c h i e r b a ~ m ~ published ~ ~ , ~ ~ ' ,some ~ ~ ~data on sorption of ethers and reported that moisturized starch takes up 1,4-dioxane when boiled under reflux. Diethyl ether and tetrahydrofuran complex more readily with air-dried starch than with oven-dried starch (see Table XXXIII ).

8. Aldehydes Earlier it was considered that formaldehyde adsorbs onto starch:l9 but later papers have shown that chemical reaction takes place with the formation of acetals and h e m i a ~ e t a l s . ~ ~ ~ ~ ' ~ ' Studies on complexes of higher aldehydes with starch were performed with a view to preserving natural food aromas. Among aldehydes, only trichloroacetaldehyde (chloral) has been studied extensively as a coacervant

366

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

TABLE XXXIII Complexation of Ethers by Potato S t a r ~ h ~ ~ ~ ~ @ * Preparation Method Ether Diethyl ether

Tetrahydrofuran 1.4-Dioxane

Ether Content, YO

Water Content in Starch, YO

Temp.

Source

3.3-3.8

20

Room temp.

5.5-6.1

40

Room temp.

3.2-3.6

20

Room temp.

5.0-7.0

20

Reflux

6.8-6.9 0.6-1.1 7.0-7.9 0.5-0.7 1.0-1.9

40 20 Vacuum-dried 20 Vacuum-dried

Starch-methanol complex Starch-methanol complex Starch-acetone complex Starch-acetone complex Native starch Native starch Native starch Native starch Native starch

Reflux Room temp. Reflux Room temp. Reflux

of and as an agent for starch f r a c t i o n a t i ~ n .Aromatic ~ ~ ~ . ~ ~alde~ hydes also readily undergo inclusion in Binding parameters and X-ray diffraction patterns of the complex of starch with 1-decanal do not differ significantly from corresponding analyses performed using l - d e c a n 0 1 . 6 ~The ~ ~ ~temperatures ~~ of formation of the aldehyde complexes are likewise close to those for relevant starch-alcohol complexes.673~hRn Analysis of the binding sites of the complex suggests that both amylose and amylopectin are involved in complexation, but these complexes are rather weak.717 The complexation of vanillin by starch is difficult and proceeds slowly over approximately 7 weeks. Among three varieties of starch (potato, waxy maize, and maize), potato starch is the most effective complexant. Gelatinized starch does not provide a suitable matrix to allow vanillin to be readily extracted.724Data from Maier and B a ~ eindicate r ~ ~ that ~ dry vanillin is better sorbed by amylopectin, and moist vanillin is equally well sorbed by both amylose and amylopectin. 9. Ketones

Acetone readily adsorbs on starch and is better sorbed on air-dried starch than on oven-dried starch. Complexation with the solvent boiling under reflux gives better yields than complexation at room temperature. The adsorption depends on the starch variety and decreases in the order po-

COMPLEXES OF STARCH WITH ORGANIC GUESTS

367

tat0 > cassava > wheat > maize. The overall amount of acetone sorbed ranges6SY.6Kl .682 from 4.2 to 2.6%. Higher temperatures favor the formation of ketone complexes.673~6Ko Comparative data are available for complexes of (-)-menthol and menthone; the X-ray diffraction patterns of these complexes are similar in both cases, but the binding parameter is slightly higher for menthone.6s6Menthone sorbs on starch solely by one Extensive X-ray diffraction studies were performed by Takeo and K ~ g on e ~ ~ ~ complexes of amylose with a series of n-aliphatic ketones of different chain length and different positions and numbers of the carbonyl groups. It was reported that the radius and chain length of the guest molecule are critical factors which determine the characteristics of the packing inside the helix. Butanone moderately alters the characteristics of gelation of potato starch and significantly changes the appearance of granules under normal and polarized

10. Carboxylic Acids Sorption of carboxylic acids on starch is useful in their thin-layer chromatograhic separation.727Amino acids are particularly well separated on thin layers of starch (see r e v i e ~ s ~ ~ ' Rice - ~ ~ starch ~ ) . is suitable for this purpose, whereas maize starch is not. Starch has been used for resolution of raceAgain, only a few studies are available on the adsorption of low molecular weight fatty acids on s t a r ~ h .Results ~ ~ ~ *indicate ~ ~ ~ that the adsorption follows the Freundlich isotherm (that is, chemisorption can be ruled out). The results also indicate that acetic acid is adsorbed onto potato starch more quickly and in greater quantities than propanoic acid. There is a rough reciprocal relationship between the number of carbon atoms in the fatty acid chain and the temperature of complex formaSuch complexation can be monitored by IR spectroscopy, as characteristic vibrations (mainly w , ~ ) undergo significant shifts.674Much more attention has been paid to complexes of fatty acids in the formation of starch-lipid complexes, and also in native starch, which usually contains higher fatty acids (in rice s t a r ~ h , 7 ~corn ~ v s~ t~a~r ~ h , ~ potato ~ ~ - ~starch73y) ~' and lipids.742M e r ~ k e observed l ~ ~ ~ that the adsorption of fatty acids is a function of the capillarity of starch. Further studies provide evidence that fatty acids increase the viscosity of gels of various starches, provided that they are nonwaxy, amylose varieties. Properties are obviously dependent on the amount of fatty material, the length of the fatty acid chain, the concentration of amylose, and the moisture content in the Starch hydrolyzed with alpha-amylase increases adsorption of fatty On the other hand, complexed fatty acids inhibit alpha-amylolytic degradation

368

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

30

60

90 120 Ti me,min

FIG.45.-Decomposition to glucose by alpha amylase of complexes of starch with various fatty acids given as the function of time. 1, behenic acid; 2, arachic acid; 3, octadecanoic acid; 4, hexadecanoic acid; tetradecanoic acid; decanoic acid; 7, hexoctanoic acid; 8, pure amylose. (By permission from Acker and Brauner-Glaesner.””’)

of starch in the manner presented746in Fig. 45. It may be seen from this figure that the inhibition increases with the length of the hydrophobic alkyl chain of the acids. Fatty acids included in starch cause swelling and solubilization of starch granules. Table XXXIV demonstrates this effect

TABLE XXXIV Effect of Fatty Acids on the Swelling and Solubility of Potato Starch747at 85°C Acid

Swelling Power

Solubility, YO

Arachidic Decanoic Dodeca noic Hexadecanoic LinoIeic Octadecanoic Octanoic Oleic Ricinoleic Tetradecanoic

29.9 19.3 14.9 13.5 16.4 20.8 23.3 13.1 14.7 11.4

3.2 13.6 2.8 1.3 3.9 1.7 13.6 0.9 3.1 1.2

COMPLEXES OF STARCH WITH ORGANIC GUESTS

369

Temp.’C 0

15 .$

3m 800

0

L

2 600

r

102

v)

5

3 400

UI

5 200 I I‘

0

. ! I

>

I

,

60

30

90

120

150

180

30

60

Time, min

90

120

150

180

Time,min

FIG.46.-Effect of various amounts of fatty acids on the Brabender viscosity (in B.U.) of potato starch. Starch concentration is 20 g/500 mL. Left side: effect of various concentrations of octadecanoic acid; right side: effect of various fatty acids at 1% concentration on dry starch basis (1, no adjunct; 2, caprylic; 3, lauric; 4, myristic; 5, arachidic; 6, stearic). (Reprinted with permission from V. M. Gray and T. J. Schoch, Staerke, 14 (1962) 239-246.)

for various acids in potato As shown in Fig. 46, the viscosity of gels depends on the acid and its concentration in starch. The preparation of starch-fatty acid complexes is based on the use of hydrophobic solvents, which in turn open the starch lattice for penetration by acids. Such solvent molecules can become guests of inclusion complexes and are subsequently displaced by fatty acids. Extrusion has been found useful for the synthesis of such c o m p l e x e ~ . ’ ~ Starch ~ , ~ ~should ~ be defatted prior to complexation by using m e t h a n ~ l ? ~ ~Cellosolve, .~~’ or 80% 1,4d i o ~ a n e . ~ ”Table ’ - ~ ~ XXXV ~ summarizes the results of a classical preparain Fig. 47, the amount of complex formation by extrusion t i ~ n . As ~ ~shown ’ is not linearly proportional to the concentration of fatty acids added.74yIn

TABLE XXXV Absorption of Fatty Acids, wt%, by Amylose at Different Moisture Levels”’ Amylose Corn Tapioca Retrograded Amorphous

Moisture Content

Oleic Acid

1.62 7.26 1.62 7.11 1.62 6.81 1.62 6.81

0.1 1.90 0.1 1.91 0 0.35 0 0.1

Hexadecanoic 3.40

0.06

370

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

U c

OA.* LA

60

E

n

II

2c

- . . 1.0

2.0

3.0

50

4.0

60

7.0

8.0

Lipids, '10

FIG. 47.-Effect of fatty acids on the formation of complexes with wheat (upper OA+LA and SA curves) and potato (lower OA+LA and SA curves) starch. OA, oleic acid; LA, linoleic acid; SA, octadecanoic a~id.7~'

every case, a saturation value of the fatty acid concentration is achieved (for instance, approximately 2 and 3% for potato and wheat starch, respectively). The practical value of wheat starch complexes (extrudates), given in terms of the characteristics of gelation, is given in Table XXXVI.74x

TABLE XXXVI Characteristics of Gelation of Wheat Starch-Lipid E ~ t r u d a t e ' ~ Characteristics of Gelation" Lipid Added Noneh None' Decanoic acid Hexadecanoic acid Octadecanoic acid Behenic Oleic/linoleic acid

Amount of Lipid Added YO

A

B

C

D

E

600 280 20 40 45 63 42

92 30

3.0 3.0 2.5 3.0 2.5

79 None None 30 30 30 30

90 84 None None None 92 None

1220 210 20 42 40 78 SO

92 92 92 92 ~~

A. Time at the first increase of the viscosity; B, viscosity (in Brabender units) at 96°C; C, time at the beginning of cooling; D. time at which the increase of viscosity is observed; E. viscosity after cooling to 50°C.

"The characteristics of gelation of the native starch. ' The characteristics of gelation of extruded starch without any lipid present.

COMPLEXES OF STARCH WITH ORGANIC GUESTS

371

Szejtli and Banky-Eloed optimized conditions for the formation of amylose complexes with unsaturated fatty The inhibiting effect of fatty acids on the blue reaction of amylose suggests that fatty acids are adsorbed by the amylose helix.751 X-ray diffraction patterns of amylose complexes with oleic, octadecanoic, hexadecanoic, and dodecanoic acids are very similar to one another. A key difference is that the amylose helix of the complex with dodecanoic acid has 17.6 glucose units per molecule of acid, and compounds with hexadecanoic acid and oleic acid have 22.6 and 25 glucose units per acid molecule, respectively. The diameters of the cavities in these three complexes are 19, 24, and 27 A, respectively. In amylose complexes the sorption capacities with respect to these acids are very similar. Amylopectin accepts a negligible amount of fatty acids, as shown in Table XXXVII for hexadecanoic (see also a paper by S c h o ~ h ~ ~The ' ) . X-ray diffraction patterns for pairs of hexanoic and oleic acids as well as octadecanoic and linoleic acids are also similar. Binding parameters for all those acids are of the same order of magnitude, but they increase with the chain length of the included acid.656 X-ray diffraction of a series of amylose complexes with lower and higher fatty acids revealed that the crystal structures depend on whether amylose was complexed in the dry or wet state. Both the 6, and 71 helical conformations of amylose were found in these complexes. The conformation appears to depend on the length of the hydrophobic moiety. Dry amylose forms crystalline complexes with a unit cell identical to that of the anhydrous 1-butanol-starch complex (lattice parameters a = b = 25.6 An orthorhombic unit cell was proposed for the 7, -helical structure of the wet complexes of monobasic acids (acetic, butanoic, pentanoic, hexanoic,

A).

TABLE XXXVIl Binding of Hexadecanoic Acid by Amylose and A m y I ~ p e c t i n ~ ~ * Hexadecanoic Acid Bound, wt% Amylose Variety Acid Added, g

V

B

Amylopectin

0.2 0.5 1.o 1.5 2.0 3.0 4.0

0.84-1.09 1.53-1.84 1.94-2.14 2.95-3.26 2.90-3.55 3.80-4.50 4.02-4.03

0.23 0.23 0.29 0.22 0.19 0.18 0.18

0.10 0.07-0.15 0.07 0.21 0.05-0.12 0.15 0.21

372

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

octanoic, dodecanoic, hexadecanoic, octadecanqic, undecylenic, elaidic, oleic, and linoleic; lattice parameters a = 13.7 A, b = 25.6 A, and c = 7.7 A). Propanoic acid gives rise to three kinds of X-ray diffraction patterns depending on the acid-to-amylose ratio. Dibasic acids give complexes with diffraction patterns that are characteristic of either the orthorhombic or hexagonal crystal structures. ’ ~ complexes ~ of corn starch with lower dioic Studies by Tomasik et ~ 1 . on acids [H02C-(CH2),-C02Hwith n = 0-41 revealed that oxalic acid forms a surface complex, with both of the carboxylic groups involved in interactions with the hydroxyl groups of the glucose residues. Malonic acid, which takes the form of an intramolecular, six-membered chelate, also reacts on the surface of starch, a process which involves interaction with only one carboxylic group. Succinic, glutaric, and adipic acids seem to enter the interior of the amylose helix. In all cases, complexes contain dioic acids at concentrations of approximately wt %. Inclusion protects unsaturated fatty acids from aging; however, this protection is not perfect, as amylose itself also complexes o ~ y g e n ~(see ~~.~’~ Fig. 48). Unsaturated acids have a specific pattern of the carbon chain because at least two sp2-hybridizedcarbon atoms are present, causing geometrical isomerism. The trans-isomer does not fit perfectly into the cavity of amylose. Another report indicates that starch complexation with tannic acid has no effect on its activity against experimental ulcers in laboratory rats.757

11. Carboxylic Esters Comparison of the sorption behavior of acetic acid and its ethyl ester (see Table XXIII)674reveals that ester sorption is slower and less efficient than that of the parent acid. The low yield of adsorption of diethyl malo-

f-#

100 l2OI

20

40 60 80 Time ,h

FIG.48.-Oxygen consumption of fatty acids complexed by amylose (I, 1 mg fatty acid; 2, 16.4 rng fatty acid; 3. 430 mg amylose). (Reprinted with permission from J. Szejtli and E. Banky-Eloed, Staerke, 27 (1975) 368-376.)

COMPLEXES OF STARCH WITH ORGANIC GUESTS

373

nate673suggests that this is a general property of esters. Thin-layer chromatography on rice and maize starch demonstrated the effect of complexation of esters of 3,5-dinitrobenzoic acid and alcohols, with the carbon chain from C1 to Cz0. A general trend is observed between the RF value and the length of the chain of the esterifying alcohol. Coumarin, which may be regarded as lactone, is sorbed on amylose and amylopectin. In the dry state this lactone is better sorbed on amylopectin, although moist coumarin is equally well sorbed on both of these polysaccharides.674It was also reported that breakdown of acetylcholine is reduced by inclusion in starch.759

12. Nitriles Conditioning in acetonitrile has significant effects on the characteristics of gelation of starch. It appears to act by ordering of the starch molecules. It increases the tendency of gels towards retrogradation. The appearance of starch granules is significantly affected on contact with acetonitrile, which suggests that the granules are easily penetrated.6x3@"

13. Amines

Sorption of amines on starch was recognized760as early as 1910 in studies of the interactions between starch and piperidine. Experiments with starch and 1-butylamine show extraordinarily high and fast adsorption. The equilibrium concentration of that amine reaches 1982 mg/g of starch, as compared to n-hexane (6 mg/g), ethyl acetate (27 mg/g), and ethanol (208 mg/ 8). Desorption is, in fact, also significant, but is much lower than in the case of the other complexes just mentioned. Because of their basic properties, amines decompose their host molecule.674Less-basic amines, such as aromatic t r y p ~ f l a v i n ~and ~ l aliphatic amine salts,'62 can be included into starch. Particular attention has been devoted to the interaction of starch with a specific tertiary amine, namely pyridine. Pyridine readily sorbs on starch, and the extent of complexation depends on the starch-to-pyridine ratio.h7',674,680 Despite the fact that pyridine has a higher basicity than do aliphatic amines, it does not compose starch to a significant large extent.669 Quinolineh7' and p y r a ~ i n are e ~ sorbed ~~ on starch in much smaller amounts. Pyridine, especially aqueous pyridine, also causes swelling of s t a r ~ h . ~ ~ ~ - ~ ~ Figure 49 shows that the swelling kinetics of potato starch depend on the concentration of aqueous pyridine. In addition, swelling kinetics depend on the variety of The affinity towards swelling decreases in the order potato > wheat > maize > rice starch. A r n y l ~ s e ~and ~ ~ amylopec,~~' tin76xcomplexes with pyridine can be prepared in crystalline forms. This process was utilized in starch fractionation, and amylopectin of 98%purity

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

314

60 E

50

0.

-2 430o -&

.-

f 3

m

20

lo o

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 Tirne,h

FIG.49.-Kinetics

of swelling starch as a function of the water content.77s

could be obtained. In addition, pyridine increases the gelation temperature of potato starch appreciably, and significantly affects the entire characteristics of g e l a t i ~ n . ~ ' ~ . ~ ~ 14. Carboxyamides

According to Banks and G r e n ~ o o d formamide ~~' increases the proportion of coiled amylose, but it is not able to completely transform amylose into a helical structure. As with pyridine, N,N'-dimethylformamide significantly affects the characteristics of gelation of potato starch. Based on thermal analysis, there is a suggestion that a reaction may occur between starch and that amide683~6'4 on 3 h of conditioning at 100 "C. Apart from various chemical modifications of starch with urea (see, for instance, Sroczynski et u L ~ ' ~ )a, true inclusion complex of urea with starch (17 :83) was prepared, and its usefulness in urea feeding was e~tablished.~~' It was reported that increases in the ammonia concentration in the blood of ruminants fed with this complex are generally much slower, and lower than in the case of the administration of urea by itself (Fig. 50). 15. Vitamins

It has been found that glucose, sucrose, casein, albumin, sodium chloride, flour groats, and starch stabilize ascorbic acid (vitamin C).771The addition of 5% of starch inhibits the decomposition of ascorbic Studies on the stability of ascorbic acid, sodium ascorbate, erythorbic acid, and sodium erythorbate showed that some stabilization is observed after the addition of 8% It was reported that the interaction is purely physical in nature.774

COMPLEXES OF STARCH WITH ORGANIC GUESTS

315

60 0

s 500

F- 400 0

I

z

; 300

0

m

200

100

I

I

1

2

L

I

3 4 Time,h

5

6

FIG.SO.--In vivo experiments with rumen-fistulated lambs with urea and starch-urea complex, measured as the concentration of ammonia in blood. (Reprinted with permission from J. Hollo, L. Fodor, and S . Gal, Stuerke, 31 (1979) 303-306.)

Potato starch adsorbs more than 2 mg of thiamine per gram. This vitamin is stable on storage at 38°C for 2 months and can be eluted by a 5% aqueous solution of sodium 16. Sulfates and Sulfonates (Surfactants)

Salts of long-chain alkyl sulfates and sulfonates are established surfactants. Thorough studies by S a i t and ~ ~ then ~ ~ by Yamamoto et ~ 1 with. sodium dodecylsulfate (SDS) on starch and amylose, respectively, revealed that a complex is formed in both cases. The long-chain anion occupies the interior of the starch helix, and the cations remain outside. Figure 51 illustrates that the response of a starch solution to an increase of SDS concentration is not linearly proportional to the reduced specific viscosity of the solution. The effect of SDS depends on the specific mode of its preparation and on the starch variety. The same trends are observed for such cationic detergents as cetyltrimethylammonium bromide. Such detergents cooperate with mineral salts, and their behavior becomes more like that of emulsifiers. Such behavior is specific for amylose. It is possible that amylopectin also interacts with detergents, but little is known about the nature of these interaction^.^'^ In general, anionic surfactants (monoglycerides and alkyl and aryl sulfates) restrict the hydration of starch and swelling. In contrast, cationic

~

~

~

376

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

-

0

0

02

04

06

Sodium Dodecyl Sulfate ,%

FIG.51.-Reduced specific viscosity of 0.93%starch solution as a function of concentration of sodium dodecylsulfate. (Reprinted with permission from S. Saito, Kolloid-Z., 154 (1957) 19-29.)

surfactants (quaternary ammonium salts) significantly increase hydration, and they reduce the swelling and solubilization of In this manner, water-soluble polysaccharides can be p r e ~ i p i t a t e d . ~ ' ~ . ~ ~ ~ The complexation of starch and thin-boiled starches with alkyl and aryl sulfonates gives a product that is readily soluble in warm water. This complexation also decreases the temperature of maximum swelling. Enzymic susceptibility is decreased and retrogradation is impeded.780 VIII. COMPLEXES WITH DYES Studies on the dyeing of starch are dated as early as the end of the nineteenth century, when the first observation was published on selective dyeing.781Because dyes belong to many chemical groups, the problem of dye complexation is rather involved.782However, this situation presents an exciting challenge for analysts. For example, it provided an excellent opportunity for differentiating starch varieties and for developing insight '~ also into the structure of starch dyes by selective d ~ e i n g . ~ ' ~It- ~should be noted that some dyes adsorb directly on starch and some of them merely impregnate the granules. For example, potato starch adsorbs Berlin Blue when impregnated with ferric chloride in solution with subsequent addition of potassium f e r r ~ c y a n i d e . ~ ~ ~ Several dye coloration scales are used to characterize starch varieties. Perhaps the oldest is the differentiation between starches based on the uptake of Saphranin and Gentiana Violet (see Table XXXVIII).787Cov e l l presented ~ ~ ~ ~ another coloration scale which is based on the use of six common acidic and basic dyes (see Table XXXIX). Like the Saphranin and Gentiana Violet dyes, these dyes adsorb directly on starch. Table XL presents a list of synthetic dyes tested in starch dyeing.78'.790Z ~ i k k e r ~ ~ ' observed the reactions of mechanically damaged starch granules and amylo-

COMPLEXES OF STARCH WITH ORGANIC GUESTS

311

TABLE XXXVIII Dyeability of Starches with Sapbranin and Gentiana Violet on the 15-Point Scalem7 Starch Source

Gentiana Violet

Saphranin

Aesculus hippocastanum Andropogon sorghum var. (W.K. Corn) Andropogon sorghum var. (Y.B. Sorgh.) Arum cornutum Arum italicum Avena sativaa var. Batatas edulis Canna edulis Canna roscoeana Canna var. (Jean Tissot) Castanea americana Castanea pumila Curcuma longa Curcunia petiolata Dolichos lahlab Hordeum sativum var. Iris alata Iris florentina Iris tingitana Jatropha curcas Lathyrus magellanicus var. albus Lathyrus odoratus var. Shahzada Lens esculenta Manihot utilissinia Maranta arundinacea Maranta leuconelira Musa cavendishii Musa cavendishii (Green fruit) Musa ensete Musa sapientum Oryza sativa var. Panicum crus-galli var. Phaseolus hinatus var. Phaseolus vulgaris var. Pisum sativum var. (Eugenie, yellow) Pisum sativum var. (Mam. G . Seeded) Polygonurn fagopyrum var. Quercus a h a Quercits rubra Secale cereale var. (Mammoth winter) Secalr cereale var. (Spring) Solanuni tiiberosurn Tacca pinnatifada

4 4 3.5 9.2 4 4 1 8.5 10 10.6 1 1.6 1 1.5 4

4 4 3.5 8.2 1 4 8.6 10 10 11.6 0.2 0.8 7 7.5 4 1 7 4 4.6 8.5 4.8 4 4 10 8.5 4 8.5 8.5 10.8 9.5 4 4 3.5 4 1 1.6 4 1 1.5 2.5 4 14 4

1 1 4 4.6 8.5 4.8 4 4 1 1 1 8.5 9.5 9.2 10.6 4 4 3.5 4 1 1.6 1

1 1 2.5 4 14 4

(continues)

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

378

TABLE XXXVIII (Continued)

Starch Source Triticum sativum var. vulgare Vicia faba Vicia sativa Vicia villosa Zea mays var. Everta (Golden Queen) Zea mays var. Everta (white rice) Zea mays var. Indurata Zea mays var. Saccharata Zingiber oncinale Zingiber offkinale var. (Jamaica)

Gentiana Violet

Saphranin

1 1.5 1 0.5 4 3.25 4 1 8.5 7.5

4 4.5

4 3.5 1 0.8 3.8 0.8 4 3.2

pectin bags with a variety of dyes (Table XLI). Rassow and Lobenstein7’* proposed characterizing native and processed starch based on their sorption behavior with respect to basic, acidic, and direct dyes. Gelation can also change the adsorptivity of starch towards dyes, depending on the starch variety and the type of dye. Schulz and S t e i n h ~ f presented f~~~ a coloration scale for the behavior of 5 varieties of starch as a function of 13 dyes (Table XLII). H ~ m b e r g e rand ~ ~ Seidemann795 ~ also proposed semiquantitative scales (Table XLIII). Huebner and V e n k a t a r a m a r ~studied ~ ~ ~ sorption of various dyes on starch of different varieties in air-dried and gelatinized forms (Table XLIV). Later studies by K ~ b a r n o t o ~ indicate ’~ that basic dyes adsorb to a greater extent on larger starch granules, whereas acidic dyes perform better on small granules. Neutral dyes adsorb independently of

TABLE XXXIX Dyeing of Starch with Acidic and Basic Dyesm

Fuchsin Starch Variety

Acidic

Basic

Methyl Violet

Methylene Blue

Potato Wheat Barley Rye Oat Rice Marantha Pea Bean

3+ 2+ 3+ 1+ I+ 1+ 1+ 2+ 1+

3+ 2+ 1+ 2+

3+ 2+ 2+ 2+

1+

1+

1+ I+ 2+ 1+

1+ 1+ 2+ I+

3+ 1+ 1+ 1+ 1+ 2+ I+ 0 0

Congo Red 0

I+ I+ I+ 0

0 I+ 0 0

Eosin 1+ I+ 1+ I+ I+ 0 I+ 1+ I+

COMPLEXES OF STARCH WITH ORGANIC GUESTS

TABLE XL Dyeing of Potato Starch with Coal-TarDyesm Little or No Dyeing Effect

Medium Dyeing Effect

Strong Dyeing Effect

Alizarin Yellow R Azo Bordeaux Azofuchsin B Cottonwool Yellow Benzopurpurin 10B Bordeaux Brilliant Crocein 3B Quinoline Yellow Chromic Brown R O Chrysoidine Diamino Bordeaux S Diamino Brown B Diamino Brown R Diamino Brown V Diamino Scarlett Diamino Deep Black 00 Direct Yellow G Direct Orange 2R Genuine Brown Genuine Acid Fuchsin B Eosin A Erythrosine Extra Fuchsin S Guinea Green B Hessian Purple NR Columbian Black Naphthol Yellow S Nyanza Black Orange I1 Patent Blue A Picric Acid Ponceau 4GB Primuline Resorcin Yellow Rose lndulin 2G Acid Violet 5BN Acid Violet 6B Salm Red Tartrazin

Alkaline Blue Alkaline Violet Hessian Brilliant Purple Hessian Yellow Towel Orange

Auramin 0 Bismarck Brown Extra Brilliant Green Chrysoidin A Diamin Blue BB Genuine Blue R Fuchsin Indazin M Janus Blue B Janus Blue R Janus Yellow G Cristal Violet Methylene Blue Neutral Blue Neutral Red Neutral Violet Parafuchsin Phosphine N Pyronin G Rhoduline Red Rhoduline Violet

319

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

380

TABLE XLI Behavior of Ground Starch and Amylopectin Granules with Respect to Organic Dyes"' Dye Nitro dyes Picric Acid Martius Yellow Naphthol Yellow S Azo Dyes Monoazo dyes Helianthine Orange G Chrysoidine Bismarck Brown Croceine Orange Ponceau 6R Bordeaux G Diazo dyes Brilliant Croceine Towel Red Biebrich Scarlett Chrysophenine Brilliant Yellow Direct Yellow Benzorit Benzazurine Benzo Blue 2B Benzo Orange Benzo Olive Benzopurpurine Benzo Blue-black Chrysamine Congo Red Congo Orange Brilliant Purpurine Benzo Brilliant Green Delta Purpurine Direct Black Direct Blue Toluine Orange " GS = Ground starch. A = Amylopectin.

+ = Strong dyeing effect. -t =

-

=

Weak dyeing effect. N o dyeing effect.

GS" -

-

Ab

Dye Acetone dyes (carbonyl dyes) Hematein Acid Carmin Ammonium Quinoline Yellow Acetonimino dyes Primulin

-

+ + -

-

+ -

rf.

+ + + + -

+

+ + + + + + + + + + + + +

Indigo dyes Indigo Carmin

Quinone Dyes Anthracene dyes Purpurine (Potassium Salt) Cyanine Quinimido dyes Cresil Brilliant Blue Magdala Red Methylene Blue Neo Blue Neutral Red Nigrosin e Saphranine Triphenylmethane dyes Erythrosine Eosine Koralline Fuchsin Acid Fuchsin Malachite Green Acid Green Iodine Green Gentiana Violet Acid Violet Water Blue Cottonwool Blue Toluidine Blue

GS"

Ab

381

COMPLEXES OF STARCH WITH ORGANIC GUESTS

TABLE XLII Dyeing of Starch Varietiesam3 Potato Dye Mixture of Black, White and Red Cresyl Violet Methyl Green Nigrosine-Sudan-Fuchsin Thionine Congo Red Gentiana Violet Neutral Red Bismarck Brown Methylene Blue Bromine water Metachrome Red Malachite Green Triacid mixture

A

B

Wheat

A

B

W

P

-

b

2 Ig

Ig

-

Ib Ib v

-

-

Y

-

bg Ib

Rye

P

-

dp Iv

-

-

-

-

_

b

gb

-

_

A W

Maize B

P

db

?lb

Ib

IP -

-

P

L

V

_

IY Ib

_

A

+ -

Rice

~

B

A

B

P

-

IP

-

Ib

-

-

-

Lv

-

IP Iv IP -

-

dP Ili IP 1Y Ib

Iv P IY b

-

b

_

~~

A. intact starch granules; B, swollen starch granules; b, blue; d, dark; g, green; I, light; li, lilac; p, pink; r. red: v. violet; w. white; y. yellow; 2.partly dyed; -no dye accepted. "

the granule size. Independent of the dye used, sorption is perturbed by chlorides of sodium, potassium, calcium, and barium. Lipatov"' recognized that the sorption of Methylene Blue on starch is a heterogenous neutralization reaction of neutralization in which starch acts as an acid. Adsorption isotherms of Methylene Blue on starch indicate that it is an equilibrium process and that swelling as well as other internal structural factors are responsible for the sigmoidal shape of the i ~ o t h e r m . ' ~ ~ *It' ~is' also known that the Langmuir isotherm is affected by equilibrium between the monomer and dimer forms of Methylene Blue, both of which are capable of adsorption on starch (Table XLV).'O' Anionic dyes readily adsorb on starch (Tables XXXIX-XLIII).802 However, there is evidence that this rule is violated in the case of potato s t a r ~ h . ~ "The ~ . ~simplest "~ intepretation of this fact has been presented in terms of the phosphate groups present in potato starch. A relationship exists between the phosphorus content in potato starch and the sorption capacity of that starch for Methylene Blue. The sorption follows the Langmuir isotherm. Extrapolation of the result to 0% phosphate leads to the conclusion that no Methylene Blue would be adsorbed on phosphate-free starch.'04 Methylene Blue is better adsorbed on potato starch, but is also

TABLE XLIII Dyeing of Starch Varietiesawm Potato

Wheat

Rye

Dye

A

B

A

B

A

B

A

B

A

Acid Fuchsin Bismarck Brown Brilliant Cresyl Blue Bromocresyl Green China Blue Chrysoidine Congo Red Crystal Violet Eosin, blueish Erythrosine Gentiana Violet Malachite Green Methyl Violet Neutral Red Nile Blue Saphranin Thionine Thiazole Yellow G Toluene Blue

3 0 0 2 0 4 0

4

3

3 1 3

1

0 0

2 0 2 1

4

4

3 0 1 2

4

2

2 4 0-2 4 4 1 2

0 2 3 3 2 3

0 2 2 0-1 2 0 3 1 1 3 3 1 3 0-1 2 3 2

4 1 3

3

3 3 1

1 1 2

0 3 3 0 0 1 1 0 1 2 1

3 0 0 1 0 3 0 0 0 1 3 2 1 4 2 3

1

4

1

1

2

1

2 1

1

1

4 2 4

1

4 1

4 2 0 0

1 1 1 1

3

0 2 2 0 2 0 3 1 2 3 3 1 3 0-1 3 3 2 2

1 4 1 4

2

0 1 1

1 1 1 3 1 1 2 1

2

0 2 0 1 0 0 3

2 3 2 1 2 2 1

2

Maranta

Maize

Rice

4

1

B

Pea

A

B

A

B

0

2

0

0

0

4

1

0

2 3

4

4

0

4

1 1

3

0 0 0

1

0 1 1

4 5

0 0 1

4

1

4

0 2 2

4

2

2

1

4 4

2 2

2 0-2

0

0 2 3 1 1 1 0

1

1

A. intact granules; B, swollen granules; data on a 5-point scale in which 0 = no dyeing, 1 = very weak dyeing, 2 = weak dyeing, 3 = good dyeing, 4 = strong dyeing.

COMPLEXES OF STARCH WITH ORGANIC GUESTS

383

TABLE XLIV Adsorption of Several Days on Starches of Various Origins7% Amount of Dyestuff Adsorbed, % Dye

Maize

Potato

Rice

Sago

Tapioca

Wheat

Acid Violet Benzopurpurine 48 Bismarck Brown Chrysoidine YRP Cutch Diamine Sky Blue Eosin A Indigo Carmine Magenta S Metanil Yellow Methylene Blue BB Methyl Violet Mikado Golden Yellow Naphthol Yellow S Orange 11 Ponceau R Water Blue

13-20 35 16 66 52 53 22-29 25 73-81 48 44-54 87 12 24 30

12 29

12 26

15 24

20 45

15 90

49 16 14 15 87 40 55

49 38 17 9 87

81

89

77 34 33 23 70 40 30

51 32 77 65 48

91 55 49 31 79 56 29

7 15

15 37

12 67

19 54

17 58

25 29

57

61 61

2

21 8 12 14 25

44

64

64

adsorbed on wheat and tapioca starch.'05 Starch inhibits Methylene Blue against fading.8MFluorescein, being an acidic dye, is sparingly sorbed on potato starch from very dilute aqueous solutions. The adsorbed dye retains its fluorescence, and starch granules assume an intense yellow-greenish CO~O~.~O~ The fluorescence of Acridine Orange adsorbed on potato starch depends on the concentration of that dye.'08

TABLE XLV Langmuir Constants for Absorption of Methylene Blue on Potato Starch from Aqueous Solutions at 26"c8O1 Dye Concentration

Langmuir Constants lo4 kl, L h o l

Low, predominantly monomer High. uredominantly dimer

0.466 1.54

lo-' *',

moVg

2.18 3.04

Linear Correlation Coefficient 0.996 0.998

384

PIOTR TOMASIK A N D CHRISTOPHER H. SCHILLING 1:10,000 and more <1:10,000 1:lMXI <1:100 1:100

pure green greenish yellow to yellow green yellow yellow-red red

The authorxo8and later Badenhuizenm' have attempted to differentiate the dyeing behavior of amylose and amylopectin present in starch granules, but they did not succeed. Instead, the dyeing of Acridine Orange allowed distinctions to be made between the A- and B-crystallographic patterns of starch?"' Further studies"' indicate that dyeing with Acridine Orange (a basic dye) is a suitable method for detection of positive and negative charges in starch granules as well as the distribution of starch in particular organs of plants. Cross-examination by dyeing with Erythrosine B (an acidic dye) is also very useful. Adsorption of a common antiseptic-Rivanol (Zethoxy6,9-diaminoacridine lactate)-on starch has also been studied.811 Studies on the adsorption of Congo Red on s t a r ~ h ~have ~ ~ shown ~ ~ ' * that potato starch does not adsorb that dye. In contrast to Acridine Orange, this dye enables determination of the amylose content in varieties of starch. The following percentages of amylose have been reported8'': wheat, 23; corn, 15; rice, 16; tapioca, 16.5; sweet potato, 2.8; and potato, 1.8. These results are suspect because of the relatively low amylose concentrations reported, particularly €or sweet potato and potato. Sorption of dyes by cellulose is decreased by the presence of starch in the dyeing solution. Comparative studiesx13on the dyeing of cellulose and starch with either Direct Scarlet B or Chrysophenine G gave the following heats of adsorption on cellulose: 49 and 45 kJ/mol. Corresponding values for starch were 29 and 62 kJ/mol, respectively. Starch complexes with Procion Brilliant Blue R, Procion Brilliant Blue H7GS, Procion Brilliant Red 2B, and Procion Red G (all derivatives of sym-triazine) are patented for coloring artificial thread~.''~ Complexes of 2-[2-(4-hydroxy-6-methylpyrimidylazo)-4-sulfochlorido]a-naphthol with starch are patented for the determination of amylose concentration~.~'~ Konrad and MussoXl6suggested the possibility of separating enantiomers of chiral azo dyes on starch, as the sorption is enantioselective. Little is known regarding the mechanism of adsorption of dyes on starch. Several early papers accepted surface sorption, and later papers suggest capillary Fluorescence and optical rotary dispersion studies818 of starch with Bengal Rose strongly suggest that both surface sorption and inclusion inside the amylose helix are involved. Pal et u1.56-x19 presented a fascinating conclusion from their studies on the induced dichroism of Methylene Blue and Acridine Orange on the starch-iodine complex. The

COMPLEXES OF STARCH WITH ORGANIC GUESTS

385

authors concluded that the starch-iodine complex is wrapped inside an additional helix of those dyes. It should be mentioned that some dyes are not only sorbed on starch by physical interactions: They can also cross-link starch. This can happen if a dye has suitable functional groups-for instance, Benzopurpurine, Congo Red, Chrysoidine-and if the pH permits dissociation of reaction sites in these dyes. It is understood that this cross-linkingaffects the UV absorption spectrum of the dye, and that the variety of starch has no effect on this spectrum.820 IX. COMPLEXES WITH LIPIDS

1. Introduction Several plants are common sources of plant fat (lipids). Some of them, for instance, cereals, also contain starch. Scheme 2 presents a classification of plant lipids. Lipids are not evenly distributed in starch granules. A certain proportion resides on the surfaces of granules (endosperm), and usually a much higher proportion resides as internal starch lipids. All of them are monoacyl glycerides, free fatty acids, and lysophospholipids.Cereal materials contain mainly internal starch lipids. Lipids of potato tubers reside in amyloplasts and are GLYCERIDES AND FA'ITY ACIDS Trig1ycerides Diglycerides Monoglycerides Free fatty acids STEROLS Phytosterol p-Sitosterol hexadecanoate P-Sitosterol glucoside 0-Sitosterol glucoside hexadecanoate GALACTOLIPIDS Digalactosyldiglyceride Monogalactosyldiglyceride 6-O- Acylgalactosyl monoglyceride Digalactosyl monoglyceride

PHOSPHATIDES Phosphatidylcholine Phosphatidylethanolamine

Phosphatidyl-N-acetylethanolamine Phosphatidylserine Phosphatidylinositol Phosphatidylglycerol Phosphatidic acid LYSOPHOSPHATIDES Lysophosphatidylcholine Lysophosphatidylethanolamine

Lysophosphatidyl-N-acetylethanolamine Lysophosphatidylserine Lysophosphatidylinositol

SPHINGOLIPIDS AND OTHER LIPIDS Phytosphingolipids Cerebroside Phytosphingosine Sulfolipids SCHEME2.-Review of Lipids of

386

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

mainly glucolipids and N-acylphospholipids.821This composition is typical for the majority of surface lipids.822Glucolipids are bonded to starch by hydrogen b0nds.8~~ The major differences between surface and internal lipids concern their chemical nature and extractability. Surface lipids are readily extractable, whereas internal ones are not.824In order to extract internal lipids it is necessary for solvents to penetrate the interior of granules. The application of heat and polar solvents is used for this purpose.x25 Lipids in starch have attracted the attention of food technologists and biologists. In particular, there is a wide variation of the concentration of lipid components in starches of various plants. Lipids are components which affect the characteristics of gelation of starch and the functional properties of gels?7y*382*826 Finally, there seems to be a link between the concentration of lipids in starch and biosynthesis and the degradation of starch. Various problems associated with lipids in starch have been reviewed several times (see and references therein, and papers on starch lipids in rice837,838 and potato83y).

2. Native Starch-Lipid Complexes Starch complexes with higher fatty acids consist of helical starch molecules containing the fatty acid inside the helix. These complexes are produced synthetically, and it is difficult to make a link between these complexes and the structures of natural starch-lipid complexes. Natural lipids are usually more complex and more bulky compounds, for which not enough space is available inside the starch helix. X-ray diffraction studies of cereal grains do not reveal the characteristic V-pattern of starch, and therefore the helical structure of starch inside these grains can be in little doubt. On the other hand, random V-type structures are reported in rice starch.84" Thus far there is little experimental evidence that starch-lipid (except starch-fatty acid) complexes have a common helical structure. For instance, amylose-bound lysophosphatidylcholine is attacked by phospholipase D. Because that lysophospholipid is not simultaneously attacked by acylhydrolases, it may be assumed that at least part of the lysophospholipid is protected by immersion inside the starch helix (see Fig. 52). Morrison8*'demonstrated that starch lipids in wheat are resistant to chlorination. This result may be explained by assuming that lipids are well protected by being complexed inside the amylose helix. However, it is also possible that the resistance to chlorination is due to protection by the granule shell. Studies on the extractability of lipids from oat starch show that the percentages of the total lipids extracted are 36-48% by cold extraction and 46-54% by hot extraction, while 6-8% remains n~nextractable."~~ Differences in the swelling of granules have been observed that are two-

COMPLEXES OF STARCH WITH ORGANIC GUESTS

0

II Choline-0- p - 0

I

387

0

- CH2-

Phospholipase D

O-CHOH-CHZ-O

II -C-(-fatty

acid chain- J -CH3

r Phospholipase A

(Lyso PC acyl hydrolase)

FIG.52.-Sites of action of phospholipases A and D on lysophosphatidylcholine. The horizontal lines indicate the portion of the lipid molecule assumed to be complexed with amylose. (Reprinted with permission from T. Gaillard, Recent Adv. Phytochem., 17 (1983) 111136.)

dimensional in wheat, barley, and rye, and three-dimensional in other cereal

st arc he^.^'.'^^ Moreover, the lipid content in large granules was found to be proportional to the surface area; in small granules the lipid content was proportional to the granule volume.843Such morphological differences suggest that the locations of lipids present in starch vary from one variety to another. Regardless of the situation of lipids in native complexes, such complexes can be synthetically reconstructed, although their chemical and structural properties then differ from those of naturally occuring complexes. For instance, the syntheticw complex of starch with lysolecithin is weakly bound and easily extracted, in contrast to its natural complex.845Studies illustrate that the reconstruction of native rice starch by by Hibi et dK4' the defatting and refatting of starch yields a product of the same crystalline pattern, but having a different tendency toward retrogradation. Refatted starch retrogrades differently from native starch and equally as well as defatted starch (Fig. 53). These results suggest that there could be a difference in the functional, technological, and nutritive properties of such complexes. For instance, inclusion complexes of lipids can limit the digestion of host molecule, as demonstrated with the complex of lysolecithin with star~h.~' 3. Preparation Methods KrogM8made an extensive comparison of two methods for preparing amylose complexes with the compounds shown in Table XXIV. The techniques differ from one another primarily by the method used for loading amylose with guest molecules. In Method I, amylose was treated with an aqueous dispersion of the guest molecule, followed by stirring for 30 min at 60°C (Table XLVI). In Method 11, the complex formed in Method I was cooled, centrifuged, and filtered through a sintered-glass filter. The results in both cases were monitored by reaction with iodine. There is a linear

388

PIOTR TOMASIK A N D CHRISTOPHER H. SCHILLING

Storage peri0d.h

FIG.S-Effect of lipid on starch retrogradation, measured as changes in the degree of gelatinization during the storage of cooked rice. Solid points, native rice; open points, defatted rice; solid squares, refatted rice. (Reprinted with permission from Y. Hibi, S. Kitamura, and T. Kuge, Cerenl Chem., 67 (1990) 7-10.)

relationship between the weight of the complex and the iodine affinity of the filtrate in the second method. In another study, it was reported that A similar enzymic hydrolysis of starch increases its fat ab~orptivity.'~~ method was developed by Osman et uLXs0 Model studiesxs1performed on gels and powders (microbeads) by CI8 monoglyceride revealed that complexation is always lower in powders (see Table XLVII). In both cases, the rates of complexation are similar for all types of complexation, and these rates are significantly influenced by the temperature of the process (Fig. 54). The rate of formation of an inclusion complex depends on the method of preparing monoglyceride samples.x52 For example, monoglycerides can be applied in the form of a gel, a monoglyceride hydrate, or a powder. The rate of complexation decreases in this sequence. Raising the temperature increases the rate of c o m p l e ~ a t i o n . ~ ~ ~ Hot extrusion and cooking are important methods. Japanese workersgs4 proposed a method of preparing the lecithin-starch complex by autoclaving at 120-130°C and continuously stirring an aqueous mixture of potato starch and soybean lecithin. Mercier et uLXs5 extruded manioc starch at temperatures of up to 225°C. They observed that this starch loses its crystal-like order as the extrusion temperature increases. The addition of fatty acids or their monoglycerides inhibits such crystalline ordering up to at least 200°C. Figure 55 shows the effect of the extrusion temperature on various properties of tapioca starch, and Fig. 56 illustrates the effects of certain additives on the aqueous solubility of manioc starch

COMPLEXES OF STARCH WITH ORGANIC GUESTS

389

TABLE XLVI Complex Formation between Amvlose and Food Emulsifiers849 Emulsifier Added, Materials Amylose without emulsifier Distilled monoglycerides YO-92% I-monoesters Lard, hydrogenated

Lard, unhydrogenated, 45% monoolein Soybean oil, hydrogenated, 85% monostearin

YO

15.3

2.5 5 .O 10.0

5.o 5.0

Acetylated, distilled monoglycerides 50% acetylation 90% acetylation Mono- and diglycerides, 45% monoester Tetraglycerol monostearate Organic acid esters of monoglycerides Lactic ester Succinic ester Malic ester Diacetylated tartaric ester Citric ester Soy lecithin Distilled propylene glycol monostearate, 90% Propylene glycol monostearate, pure Propylene glycol monopalmitate, pure Propylene glycol monolaurate, pure "Sorbitan" mono-octadecanoate "Sorbitan" tris-(octadecanoate) Sucrose mono-octadecanoate, commercial Sucrose bis-(octadecanoate), commercials Polyoxyethylene-"sorbitan"-(20)-monooctadecanoate commercial 2-Octadecanoyl-lactate Sodium-2-octadecanoyl-lactate Calcium 2-octadecanoyl-lactate Sodium octadecanoyle-fumarate

7.4 .2 0 10.0 2.0

92

35 87

10.0 20.0 Soybean oil. unhydrogenated, 55% monolinolein

Iodine Atrinity Amylose-Complexing of Filtrate Index

5.0

1.5 0 11.0 28 8.2

10.0 20.0

2.8

10.0 10.0 2.5 5.0 5.0

11.6 15.3 13.0 11.0 10.1

5.0 2.0 5.0 5.0 5.0 20.0 5.0 5.0 5.0

11.9 10.3 5.7 9.8 7.8 0 9.8 12.8 12.9

10.0 10.0 10.0 5.0 5.0 5.0 5.0 5.0

6.9 6.2 5.3 12.6 13.3 11.3 13.8 10.4

5.o

3.2 4.3 5.4 5.0

28 34

22 63 36 49 36 16 15

5.0 5.0 5.0

18 13 26 10 32 79 72 65 67

390

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

XLVII TABLE The Effect of Ct8-Monoglycerideand Its Two Crystalline Structures on the Complexing of Soluble Potato StarchaBS1 Complexing Index of Crystalline Form of Monoglyceride ~~

~

P

Monoglyceride Conc., YO

a Gel, pH 6.5

Powder (Microbeads)

0.1 0.2 0.5 1.o 2.0 3.0 3.5

21.2 2 4.56 39.3 ? 5.2 64.2 0.5 65.7 2 0.5 67.8 ? 1.0 68.8 2 1.0 68.6 2 1.0

17.1 2 1.9 35.9 5 0.8 53.0 2.6 54.9 ? 3.4 55.8 ? 3.3 58.0 5 3.3 58.0 5 3.4

*

*

The experiments were performed at 60°C for 20 min. Standard deviations were calculated with n = 3.

(see also a patent856on the preparation of starch (sodium or potassium) 2-octadecanoyl-lactate for use in instant puddings). M e ~ s e r ’ ~performed ~,~~’ similar studies on wheat and potato starch. Figures 57 and 58 illustrate basic differences in the complexing abilities of monoglycerides, triglycerides, and emulsifiers in wheat and potato starch. It may be seen that wheat starch has a saturation limit of 4% lipids for monoglycerides and 1-1.5% for triglycerides. In potato starch, this limit for both types of lipids is approxi-

8o

t

0’-

10

15

20 25 Tim B, min

.,

30

35

FIG.54.-Complexing rate of amylose leached from starch grains which were preheated, cooled, steam-cooked, and then mixed with Cls-type monoglycerides at 50 and 60°C; 0, gel powder form.8” pH 3.5; 0,gel pH 6.5; A, gel pH 7.1;

COMPLEXES OF STARCH WITH ORGANIC GUESTS

70

95

391

135 170 200 225 Extrusion temp., 'C

FIG.%.-Effect of extrusion temperature on expansion (solid points), water absorption index (open points), water solubility index (stars), and viscosity at 50°C (triangles) of tapioca starch. (Initial moisture content was 22% on dry starch basis.) (Reprinted with permission of C. Mercier, R. Charbonniere, J. Grebaut, and J. F. de la Gueriviere, Cereal Chem., 57 (1980) 4-9.)

mately 3%. Table XLVIII also presents relative viscosities of a cold gel and the lipid solubility of several extrudates of wheat starch. These results indicate that extrusion of plain starch significantly increases the solubility.

3100

I

A

GMS

(GMSIG w)

C18

FIG.56.-Water solubility of tapioca starch and chemically modified starch extruded without and with 2% addition of fatty acids. C2, acetic acid; CI2,dodecanoic acid C14. tetradecanoic acid; Clh, hexadecanoic acid; C18,octadecanoic acid; Clx: oleic acid; C18:2, linoleic acid; CaSL, calcium octadecanoyl lactate; GMS glyceryl monooctadecanoate; GMP, glyceryl monohexadecanoate; Am, Amidan and Dm, Dimodan (mixtures of GMS and GMP). (Reprinted with permission of C. Mercier, R. Charbonniere, J. Grebaut, and J. F. de la Gueriviere, Cereal Chem., 57 (1980) 4-9.)

392

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

? E

U

Im/ ao

Lipids, %

FIG.57.-Effect of lipids on formation of complexes with wheat starch (GMO. glyceryl monooleate; GML, glyceryl monolinoleate; GMS, glyceryl monooctadecanoate; SL, soy lecithin; HPF, hardened peanut fat; SO, soy

In addition, the solubility of extrudates with lipids is always lower than that of the plain extrudate. 4. Structures and Properties of Complexes

Studies of the rheological behavior of aqueous solutions reveal that contact with litids causes the formation of a helical complex with a lipid The most convincing evidence of this molecule inside the amylose structure comes from Raman spectroscopy.R59Approximately three turns

I HPFew

GML

1.0 2.0 3.0

4.0 5D 6.0 Lipids

7.0 80

O/O

FIG.%.-Effect of lipids on the formation of starch complexes with potato starch. (HPF,,, hardened extracted peanut fat; other notation as in Fig. 57).749

COMPLEXES OF STARCH WITH ORGANIC GUESTS

393

TABLE XLVIII Solubility and Room-Temperature Viscosity of Extrudates of Wheat Starch with Lipids748

Lipid in the Extrudate None, native starch extruded starch Octadecanoic acid Oleic and linoleic acid Glycerol mono-octadecanoate Glycerol monoleate and monolinoleate Soy lecithin Soy oil

Process Relative Lipid Temperature, Viscosity, "C Solubility, YO YO Added, YO

2.5 2.5 0.4 2.5 2.5 2.5 3.0 2.0 3.0 5.0

158 162 156 151 166 156 152

1 36 3 3 25 3 3 13

147 147 147

30 29 27

100

10 11

6 11 100 110

of the amylose helix stores the carbon chain of glycerol monooctadecanoate. The size of the carbon chain of dodecanoic acid fits the dimension of the amylose cavity.860X-Ray diffraction studies of inclusion complexes with amylose revealed that the cell dimension is the same regardless of the complexed lipid. Inclusion complexes form with all of the lipids studied, except for the diglycerides of hydrogenated soybean oil. Derivatographic861 and calorimetric86'a,861b studies on lipid complexes with maize and wheat starch indicate that complexation takes place at the moment of starch gelation. The enthalpy of formation of the starch complex with lysolecithin is 5.8 J/g. The authors suggested that lipids vary in their affinity towards complex formation with starch. More extensive studies performed with potato starch by Hoover and Hadzijev862illustrate that such properties as the solubility, swelling power, viscosity, heat stability, and the water-binding capacity depend on the carbon chain length of the fatty acid associated with the complex as monoglyceride (Tables XLIX-LI). It is evident from stability-constant measurements that the monoglyceride of tetradecanoic acid forms the most stable complex. Enthalpies of melting of the complex increase proportionally with the length of the carbon chain of the fatty acid residue. Binding parameters (Table LII)717show that the complexes are weak and they can be readily decomposed by other competing agents. As shown by Kim and cyclomaltoheptaose forms binary complexes with lysolecithin and ternary complexes with lysolecithin and amylose. The complex of lysolecithin with amylose is disrupted by cyclomaltoheptaose.

PIOTR TOMASIK AND CHRISTOPHER H. S C H I L L I N G

394

TABLE XLIX Solubility, Swelling Power, Viscosity, and Transmittance of Starch-Monoglyceride Complexesss' ____

~

Viscosityb,CP Fatty Acid

Solubility", 7'

~~

Swelling Power 50°C 60°C

70°C 80'C

Transmittance YO at 520 nmd

~

None

32.1 2 1.2

171.2 t 8.5

29.73 2 0.5' 31.4 5 0.1 18.6 t 0.3 22.9 t 0.5 8.4 2 1.2 10.5 2 1.2 3.3 t 0.5 5.4 2 0.5 4.9 2 0.3 7.0 t 1.8 7.3 2 0.5 9.2 t 1.2

145.6 -+ 4.5 157.6 t 4.0 68.9 t 4.5 83.1 ? 7.5 34.2 3.5 36.2 t 1.2 16.1 t 0.9 22.6 3.5 21.6 2 2.0 27.9 2 3.2 30.2 t 2.5 35.6 t 2.5

* *

5.6 6.6 5.4 6.2 3.9 4.6 2.8 3.2 2.6 3.0 2.6 3.0 3.0 3.4

____~ a

6.7 7.7 6.3 7.2 4.6 5.2 3.4 3.8 3.2 3.6 3.2 3.6 3.6 4.0

7.6 8.6 7.2 8.0 5.4 6.0 4.3 4.6 4.0 4.2 4.0 4.2 4.5 4.8

10.8 11.8 10.1 11.0 7.6 8.4 5.0 5.6 4.5 5.0 4.5 5.0 5.2 5.8

___

54.3 68.4 49.3 61.6 37.6 44.2 27.5 32.3 22.4 24.8 24.8 27.5 28.8 33.9

___

1he lower values pertain to potassium salts of monoglycerides. The lower values pertain to gels cooled to 25°C. The standard deviations were calculated for n = 3. The upper values were obtained at 80°C.and the lower values after cooling to 25°C.

TABLE L X-Ray Diffraction Patterns of Starch-Monoglyceride Complexesss1 Lipid" None

C8 ClO c 1 2 c 1 4

Clh

cis

ClH'

Moisture Content, 70

Interplanar Spacingb

Number of Weak Spacings

Range, A

12.5 13.3 13.4 13.9 13.3 13.3 13.9 13.3

15.24m 6.07m 5.15s 3.97m 3.73m 5.22m 4.48s 6.51m 5.83m 4.67s 5.09s 4.44m 3.90m 15.78m 5.15s 4.43m 3.98m 3.67m 12.11m 5.21s 4.53s 4.17m 3.73m 5.18s 4.67s 5.90m 5.18s 4.43m 4.13m 3.70m

13 9 7 7 10 9 14 6

3.73-17.67 4.1 1-1 5.24 3.82-17.67 3.14-16.36 4.21-14.73 3.40-20.08 3.80- 19.21 3.55-15.78

The length of the acid chain is given. Only medium (m) and strong (s) intensities are reported 'The 1-monoglycerides are isolated from hydrogenated and distilled soybean oil.

a

COMPLEXES OF STARCH WITH ORGANIC GUESTS

395

TABLE L1 Starch-Lipid Complex Endotherm Characteristics as Affected by the Monoglyceride Chain LengthaBS1 ~

Complex Melting Point ("C) Regardless of Chain Length G-Transition

M2-

M2-Transition

VI

to

t,

t,

to

t,

t,

Chain Length

0.39 0.50 0.65 0.70 0.85

57 56.5 55.5 54.5

66 66 66 66

70.5 71 71 70.5

126 122 109 104 92

134 129.5 115 113 104.5

140 133 122 118.5 110

C8 Clo C12 C14 C16

Transition H,cal/g

Amylose Complexed, YO

0.71 0.86 1.43 1.78 1.75

36.5 43.8 72.9 91.2 89.6

" Starch was treated with 0.7 m M monoglycerides.

'

Values were determined at Y , = 0.85. Average T o , unit was established from linear regression analysis.

=

169.4 f 2.1"C and 113 KJlmol. The o-glucose

Rheological studies indicate that the gelation temperatures of corn and potato starch are only weakly perturbed by lipids. The addition of lipids increases the peak viscosity of wheat starch, whereas this value is decreased in the case of tapioca and potato starch.864It was suggested86sthat these differences may be attributed to the ability of monoglycerides to penetrate into the interior of starch granules, an ability which depends on granule swelling. At 30°C the bonding of monoglycerides is irreversible, regardless of the starch variety. Quantitative differences are interpreted in terms of the specific area of the granules (see Table LIII).

TABLE LII Binding of Decanal, 1-Naphthol, Glycerol Monowtadecanoate Glycerol Monohexadecanoate, and Menthone to Starch717 Binding Parameters Guest Molecule Menthone Decanal 1-Naphthol Monooctadecanoate (70°C) Monohexadecanoate (70°C)

mom 49.2 38.2 19.7 4.27 3.12

B,,,

mmollmol 43.94 13.78 62.35 9.27 10.42

h 1.43 2.10 2.22 1.96 2.75

396

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING TABLELIII Binding of Monoglycerides to Starches of Various Origins at Hexadecanoate t Octadecanoate

Starch

Rice Wheat Tapioca Potato

Specific Area, m*/g Added, mglg Starch Bound, mglg Starch Bound, mglm* 0.59 0.29 0.26 0.12

38.8 45.0 40.0 39.6

6.6 9.5 4.9 10.5

11 29 19 88

5. Functional Properties of Starch-Lipid Complexes The significance of starch-lipid complexes in bread has been reviewed.866 Earlier, the role of lipids and other emulsifiers was also r e ~ i e w e d . ~ ~ ’ , ~ ~ ~ - ~ ~ For such starchy foods as noodles, cakes, pastries, processed potato food, and puddings, lipids improve the texture. The tendency of bread to staling is also related to the presence of lipids and emulsifiers. In order to satisfy market demands, it is important to optimize the water-binding capacity, the rate of water sorption, and the swelling power. The effects of lipids on these properties is under ongoing study. The mode of application of lipids is also a factor which controls functional proper tie^.^^'-^^^^^"^ The effect of all these factors on bread quality has been r e c ~ g n i z e d . ” ~ - ~ ~ ~ The firmness of bread depends, among other things, on the rate of retrogradation of polysaccharides (namely, the amylose and amylopectin present in the flour). The rate of retrogradation of amylose is generally so high that it is quite unlikely to be the factor responsible for the staling of bread. In contrast, the relatively slow retrogradation rate of amylopectin appears to be a decisive However, the accelerating effect of amylose on the retrogradation of amylopectin is also a factor.R7sComplexation of amylose, as already described in this chapter, impedes retrogradation of amylopectin (see also papers by LorenzEZ6and Ohashi et u L , ’ ~ as ~ well as by Azudin and M o r r i s ~ n and ~ ’ ~Germani ~ ~ ~ ~et ~ 1 . ~ ~Complexation ’). should, therefore, be the most important factor controlling the firmness of bread. Additionally, it has been realizeds7’ that monoglycerides of saturated fatty acids produce better results (less staling, more firmness) than unsaturated ones. This observation was thoroughly examined by Lagendijk and Pennings,8” who indirectly checked the effect of monoglycerides of dodecanoic (GML), tetradecanoic (GMM), hexathecanoic (GMP), octadecanoic (GMS), arachidic (GMA), oleic (GMO), and linoleic (GMLi) acids on the firmness of bread. They attempted to prepare inclusion complexes of those

COMPLEXES OF STARCH WITH ORGANIC GUESTS

397

lipids with amylose and amylopectin. The results quoted in Table LIV show that, although both components of starch form complexes with lipids, amylopectin binds lipids to a considerably lesser extent. Complexes of amylopectin with unsaturated monoglycerides have not been reported. Results of the authorP6 confirm former observations that the complexation ability of the series of saturated monoglycerides with amylose reaches a maximum at the monoglyceride of tetradecanoic acid. They observed a maximum of complexation ability in the case of hexadecanoic acid monoglyceride. The ability of those monoglycerides to form complexes with amylopectin increases with increases of the chain length of the fatty acid. There is a linear relationship between the complexing capacity of monoglycerides with amylose and the compressibility values of the bread. No such relationship was observed in the case of amylopectin. The mode of application of the monoglyceride has a critical effect on the firmness of bread. For example, within a 6-day experiment, the softness of bread was best maintained when octadecanoic monoglyceride was applied in the form of gel at pH 6.8. The worst results were obtained when that ester was added in a powder form. An experiment with a mixture of mono- and diglyceride (approximate composition 1:l)applied as emulsion produced a negligible effect on bread softness (Fig. 59).853Qualitatively similar results were presented by Seibel er uf.@I The importance of the crystallinity of esters was also indicated. The a-crystalline form is preferred over the /3-form.882.883 Bourne er aLxM studied the glycolipids (sucrose mono- and dioctadecanoates) glyceryl monooctadecanoate and polyoxyethylene monooctadecanoate as antistaling agents in bread. As shown in Fig. 60, several antistaling agents give successful results on wheat starch. The intention of the authors884

TABLE LIV Content of Monoglycerides Complexed by Amylose and AmylopedineRO Amount of Monoglyceride Bound, mg

Amount of Monoglyceride Bound, g/lO-* mmol

Monoglyceride

Amylose

Amylopedin

Amylose

Amylopedin

Dodecanoate Tetradecanoate Hexadecanoate Octadecanoate Arachidate Oleate Linoleate

41.2 70.1 112.2 101.6 59.2 73.9 36.5

3.0 10.7 15.1 25.0 32.8

5.4 8.9 12.4 10.5 5.8 7.2 3.5

0.4 1.3 1.6 2.5 3.0

398

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

1400

I\

1200

800 600

400

200

1

1

2

3

4

5

6

Time, days

FIG.59.-Anti-firming effect of the monoglyceride preparations in white bread. Diglyceryl octadecanoate (DGMS) at pH 6.8 (open points), at pH 7.3 (solid points); DGMS hydrate (solid squares); DGMS hydrate powder (open squares); DGMS powder (solid triangles); mono- and diglycerideemulsion (open triangles);control (crosses). (Reprinted with permission from N. Krog and B. N. Jensen, J. Food Techno[., 5 (1970) 77-87.)

was to form a layer made of such complexes on the surfaces of swollen starch granules. Such a layer, possibly impermeable to water, should prevent escape of water from bread and thereby inhibit staling. In practice, the situation is far more complex. Gluten (a protein) also plays an important role in the properties of bread. Its reaction to water and its interaction with lipids are equally essential. Mono-, di-, and triglycerides are found in the protein fraction of flour, along with phospholipids. Starch shows a preference for bonding saturated monoglycerides and free fatty acids, whereas the protein fraction shows a preference for binding unsaturated mono glyceride^.^^^ The formation of lipid-protein complexes must also be taken into documented that monoglycerides Model studies by Strandine et dXh9 inhibit swelling and hydration of starch granules and flour when heated in diluted aqueous slurries. The soluble starch is retained within the starch

COMPLEXES OF STARCH WITH ORGANIC GUESTS

399

POEMS

1400 GMS com mercial

1000

0.00 00%

aos 0.075

VOPrecipitant FIG. 60.-Precipitation of wheat starch with lipids. (SMS, sucrose monooctadecanoate; GMS, glyceryl monooctadecanoate; POEMS, polyethylene monooctadecanoate; SDS, sucrose disoctade~anoate).~~~

granule. Decreasing the degree of starch gelatinization makes available more moisture for hydration of the gluten. Eliasson ef aLm7studied cornstarch-lipid-cationic surfactant complexes and showed that the presence of cetyltrimethylammonium bromide increases the storage modulus of the complex. The formation of inclusion complexes of lipids inside the amylose helix is not the only important factor regulating the functional properties of foodstuffs. The adsorption of lipids on starch surfaces can prevent the separation of components in frozen starch noodles. Such surface sorption reduces the viscosity and adhesiveness of the starch.888The latter property can also be important in the microencapsulation of medicines. For example, a complex of cornstarch with glucolipids has been patented as an excipient for 3-( p-chlorobenzyl)-6-methoxy-2-methylindole-l-acetic acid.88y Complexes of starch with lecithin are useful for pharmaceutical applications, as they form molding compositions with good release characteristics and dimensional stability.8wSolutions of approximately 10% of lecithin in starch are utilized for fiber sizing and as cold-soluble adhesives.891Only 3-5% of lecithin in starch produces a cold-water paste.892A complex of starch with lecithin increases the adhesiveness of some synthetic polymers.xy3

6. Digestibility of Starch-Lipid Complexes Enzymatic degradation of amylose is inhibited by complexation with

lipid^.^^^-^'^ Decreased digestibility of complexes in vifro and in vivo have been observed, and such results suggest the feasibility of enzyme-assay

400

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

determinations of starch.R95 These observations also have potential dietetic implications.The combination of starch and lipid components decreases the nutritive value of a meal, and conversely, separation of these components increases the nutritive value. Fat metabolites (such as fatty acids and monoglycerides) are adsorbed in a micellar form in the upper part of the intestine. Within this organ, these metabolites can come into contact with nondigested amylose, particularly if its form in food provides for slow amylolytic degradation (as in bread and cereals). Since approximately 1 wt% of lipids in cereal starch can complex about 5 wt% of amylose,s6' the formation of dietary fibers in the intestine is quite probable."' This possibility can positively induce peristaltic action of the human intestine and should be avoided in animal feedstuffs. ExperimentsR96in vitro indicate that there is a rather small difference in the rate of degradation by pancreatic alpha to amylase of gelatinized starch and its complex with the monoglyceride of oleic acid. The difference in this rate (given as dextrose equivalent) reaches 20%.

7. Analysis of Lipids in the Presence of Carbohydrates The problem of lipid analysis was reviewedRY7 by Menger in 1971. Several methods were developed to liberate lipids for their analytical determination. In the case of analysis of starch, the problem seems to be simpler if an enzymic method involving the thermally stable alpha amylase for starch degradation is ~ s e d . ~Analysis ~ ~ ~ of " ~intact complexes involves the routine method of iodine-binding capacity. Using this method, it was reported8" that the concentration of complexes can vary as a function of time. In the case of potato flakes with the monoglyceride of octadecanoic acid, the concentration of complexes decreases, and the loss of the complex increases with an increase in the amount of lipid added (Table LV). The formation of starch-lipid complexes can also affect amylase activity in serum, as measured by the starch-iodine method in patients treated with heparin. Heparin induces lipoprotein lipase, which generates lipids capable of amylose complexation.m The formation of complexes with lipids was utilized in the determination of amylose content in starch. Various lipids were utilized for this purpose. Kugimiya and Donovan861,861a proposed lysolecithin, whereas Sievert and HolmR61bused L-a-lysophosphatidylcholine.The formation of complexes was observed either derivatographically or calorimetrically. It was proved that complexes were formed when starch was gelatinized.

X. STARCH COMPLEXES WITH MONO-AND OLIGOSACCHARIDES Berczeller" observed that lactose and maltose exhibit negative sorption on starch in aqueous solutions. This polarimetrically monitored sorption increases with the concentration of the saccharide solution. In some pa-

COMPLEXES OF STARCH WITH ORGANIC GUESTS

401

TABLE LV Data for Potato Flakes with Glycerol Monooctadeeanoate (GMS)*" Complexed Starch, %

IBC Starchb Sample, % GMS Dry Matter %

%

Glucose %

Time, h IBC Time, h

C,

~

0

92.33

74.6

0.04

0.3

92.42

76.0

0.04

0.6

92.68

74.5

0.03

0.9

92.40

75.3

0.03

0 0.08 2 5 0 0.08 2 0 0.08 2 6.5 0 0.08 2 7

1.74 1.76 1.76 1.78 1.67 1.64 1.54 1.53 1.43 1.17 1.08 1.42 1.33 1.02 0.78

0 0.08 2

5 0 0.08 2 0 0.08 2 6.5 0 0.08 2 7

49.8 49.3 49.3 48.7 52.7 53.6 56.4 55.8 58.7 66.2 68.8 59.4 62.0 70.9 77.7

Iodine-binding capacity.

* Starch concentration.

pers?)z-yM the retention of crystalline sucrose is claimed to be the result of interactions with starch. If crystallization of sugars in the presence of starch takes place, the macrocrystal structure is changed with respect to that which is normally built up in the absence of sugars. It was observed in the case of glucoseyosand sucrosem6 that it can be an important factor in using sucrose as pharmaceutical e ~ c i p i e n t . "At ~ a certain proportion of mono- and disaccharides to starch, the crystallization of polysaccharide is perturbed. Xylose and ribose decrease the retrogradation of wheat starch with increasing sugar concentration. Fructose exhibits the opposite effect.g0* Similarly, monosaccharides (glucose and mannose) and disaccharides (sualcrose) are reported to increase the retrogradation of though the opposite effect was reported by another author in the case of wheat starch."" More extended comparative studies are lacking. Kim and D' Appolonia'" studied the effect of wheat-flour pentoglycans on the retrogradation of wheat-starch gel. It was reported that waterinsoluble pentoglycons retard retrogradation more effectively than soluble ones. In contrast to soluble pentoglycans, which interact only with arnylose, insoluble pentoglycans form complexes with amylose and amylopectin. The effect of pentoglycans on retrogradation is interpreted as hindering centers

402

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

of crystallization of starch. Pentoglycans do not influence gelatinization. Various effects of pentoglycans on breadmaking have also been rep~rted.”~-’~~ The industrially important process of sugar filtration is hindered by the presence of starch in filtered media,y15-y1’8 a fact which is not necessarily attributed to the formation of any complexes, but is instead caused by the formation of particles <2 pm in diameter. The formation of starch complexes with lower saccharides is suggested by the increased viscosity of sugar syrups, starch sols, and starch gels after the addition of y1y-y24 The addition of sucrose to a dry-like cornstarch mixture of water causes liquefaction of the mixture as a result of a decrease in water activity. This has been described by ChinachotiYZ5 as a magic trick. The same effect is caused by other sugars. Such mixtures are buoyant and viscous at the same time. They form a blue color with iodine, and this color of the complex is not changed by the addition of sugar. Pure amylose does not show the effect of the “magic trick,” but behaves analogously with respect to iodine.926This result suggests that the complexing sugar does not decoil the amylose helix and amylopectin random coils. It also suggests that migration of sugar into the cavity of the helix takes place, and it indicates that the stability constant of starch-sugar complexes is lower than that of the starchiodine complex. There have been some contradictory observations on the effects of various mono- and disaccharides on the gelatinization of starch, contradictions that result from the properties of different varieties of starch. However, the general trend observed by all authors is that increases in the sugar concentration lead to decreases in the gel viscosity (see Table LVI). It has been shown’21~’22~y27~’28 that saccharides added to starch increase the gelatinization temperature. This results from the retardation of granule s~e11ing.’~’~’~~~”’~’~’~’~~ However, it should be strongly emphasized that the effect of sugars on swelling depends on the concentration of their aqueous TABLE LVI Effect of Sugars on Gel Strength, g/cm, of Corn Starch9” Sugar Concentration, % ~

~

~

Sugar

0

5

10

20

30

50

Fructose Glucose Maltose Lactose Sucrose

149 146 148 158 151

157

158

150

145 134

140 104 94

96 75 66 60 63

42 26 n o gel

143 157

139

133 127

93 90

no gel no gel

COMPLEXES OF STARCH WITH ORGANIC GUESTS

403

solutions. Above certain concentrations, swelling does not occur.y31The majority of the foregoing effects were previously interpreted in terms of the competition of mono- and oligosaccharides with starch for water molecules necessary for solubilizing, hydration, swelling, and gelation.908~y21,Y22~ y2y~y32-y35 This competition is won by the low molecular weight saccharides, and as a consequence starch has fewer water molecules available for swelling. To prove this hypothesis, studies of water mobility in starch-sucrosewater ternary systems have been performed by I3C and I7O NMR techn i q u e ~ . Johnson ~ ~ ~ - ~et ~~ ~1 . used ' ~ ESR methods in such studies. Several investigators have shared the opinion that there are direct interactions between starch and sucrose as well as other saccharides. Gardell"' and also Brown and Frenchy48have shown that mixtures of saccharides can be separated effectively on chromatographic columns packed with starch. Brown and Frenchy4' found the following sequence of elution volumes for the following saccharides: stachyose < raffinose < lactose < glucose, which are respectively tetra-, tri-, di-, and monosaccharides. For several years, these authors assumed the formation of inclusion complexes of saccharides with starch. The foregoing chromatographic studies suggest that an essential factor in the formation of such complexes is the conformational fit of the host and guest molecules. The best conformational fit should obviously be possible with a-D-glucose and other sorbates that contain such moieties. In disaccharides, especially in sucrose, the second sugar moiety should form a branch of the main trunk of the complex, and it should introduce disorder on a macroscopic scale. However, if there are several such branches situated at a suitable distance from one another, ordering may result instead. Such ordering may arise either from direct interactions attributed to a local mutual conformational fit, or from the ordering and eventual captive interactions with water molecules. It could explain the 13C NMR results of Hansen et af."' that, on interaction of sucrose with starch, some of the carbon atoms of sucrose interact more strongly than others. It could also explain the observation by Lim et aLg5' of a decrease of the water mobility in starch after the addition of sucrose. Changes in the mobility of water in starch mixtures with other saccharides are similar to the case of mixtures with sucrose; however, the relative magnitudes differ. It was reported"' that the effectiveness of interactions of saccharides with starch correlate strongly with the number of potential hydrogen bonds offered by a given sugar molecule multiplied by the concentration of the sugar in solution (nH).These results correlate well with the temperatures of the onset of starch gelation (T,) in the presence of glucose, sucrose, maltose, and maltotriose. For a set of 12 data points, the equation nH = 1.41 Tg + 52.07 with a correlation coefficient r = 0.99 is obeyed. Also, for a set of 1 1 data points on starch mixtures with glucose, sucrose, and fructose,

404

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

the equation nH = 1.52Tg + 51.72 applies, with r = 0.95. These results suggest a conformational fit with fructose in its pyranoid tautomer in the complex. It should be noted that this correlation is opposite to that reported by Brown and French on the sorption of sugars on ~tarch."~ The enthalpies of gelation do not correlate with nH. The scatter that is observed is an indication of the complexity of the gelatinization process, a process which is not suitable for studying complexation, primarily because it depends on swelling. Spies and H o ~ e n e proposed y ~ ~ ~ that sugar molecules bound to amorphous regions of starch form bridges between chains. The complexation of sugars should retard water absorption, a fact that is observed in practice.953It signifies an increased energy requirement of gelatinization. Gelatinization temperatures obey the following sequence for the following complexes with potato starch: sucrose > glucose > maltose > ribose.y53The effect of sugars on the loss of birefrigency of starch obeys the following sequence: sucrose > glucose > fructose.9s4The effect of sugars on starch gelatinization depends on the chain length of the interacting sugar.9s2 The aforementioned branching explains this observation. Branches, and the hydrating water molecules attached to these branches, create steric hindrance for access of water molecules to starch, causing swelling and gelatinization. The effects of saccharides on starch retrogradation may be similarly interpreted. The formation of starch complexes with fructose and glucose certainly causes local ordering of the species, which can be extended to ordering on a macro scale. Sucrose, by the formation of a complex, can also produce local ordering, but its uncomplexed fructose moieties introduce disorder on a macro scale. Noncomplexing, or relatively weakly complexing, pentoses cause disorder on the micro and macro scales. Tomasik et a1.955advanced a convincing argument for the complexation of mono- and disaccharides with starch. They compared the polarimetric rate and extension of mutarotation of starch and starch-sugar mixtures. Perturbation of this process by the introduction of particular sugars accounted for the complexation. Measurements of viscosity, differential scanning calorimetry, and interpretation of Brabender amylograms suggest that starch complexes with D-glucose, D-fructose, D-galactose, D-mannose, lactose, maltose, D-xylose, and sucrose, Complexation of starch with D-ribose is doubtful, and there is no complexation with L-arabinose. There are several practical applications involving interactions between starch and saccharides. For example, starch-derived sugars are used as plasticizers for starch.956Thus, the addition of potato starch to sugar syrup increases the solution viscosity to a level where it retains gas bubbles and is suitable for producing froths.9s7Agaran, starch, and swollen Sephadex G-200 form a mixed support for zone electroph~resis.'~~ A plywood of improved strength resulted from the blending of an aqueous solution of

COMPLEXES OF STARCH WITH ORGANIC GUESTS

405

sucrose and starch or wheat flour, followed by the addition of sulfuric acid and hot pressing.”’ A mixture of agar with sucrose and starch gives a jelly of good quality.y60An oriental candy, rakhat-lukum, should also be mentioned: it is a pseudoplastic gel, and its market value depends on its viscosity and thixotropic properties, both of which are unstable. The stability of rakhat-lukum can be restored by increasing the concentration of sugar and cornstarch.’61

COMPLEXES WITH MACROMOLECULES XI. STARCH 1. Starch-Protein Complexes a. Introduction.-In this section, interactions between starch and amylose, amylopectin, nucleotides, nucleosides, and proteins are discussed. The section on carboxylic acids should also be consulted. Several observations indicate the formation of starch-protein complexes. For instance, starch precipitates serum proteins of rabbit, horse, sheep, and chicken.“* This observation seemingly indicates that the complexation has a rather universal character. On the other hand, the type of bonding of proteins from Triticum durum and Triticum sativum is specific for each of these varieties.y63The observed effects may not be associated with complex formation, but they can instead be attributed to the destruction of micelles by dehydration, followed by agglomeration.’” As in the case of starch complexes with sugars, the effect of proteins and cellulose derivatives on starch gelation can be assumed to be the result of the competition for water in solution. As a consequence, swelling is p e r t ~ r b e d . ’ ~ ~ - ~ ~ ~ Electrophoresis of proteins on starch thin layers,y69starch columns,”70 and starch gelsy71~y72 has been reviewed. Partition chromatography of ribonucleosides on starch”’ and the possibility of making plastics from starch and proteinsy74have also been discussed. The effect of protein-starch complexes on the staling of bread was discussed by H a m ~ e l . ~All ’ ~ of these studies suggest the formation of starch-protein complexes. b. Native Complexes.-Proteins in cereals and starchy plants reside as surface and internal proteins. The state of surface proteins is not well understood. It is suggested that, together with starch, they form a continuous matrix in mature Surface proteins can be separated from internal proteins by such dissociating agents as sodium dodecylsulfate. The internal portion of proteins can be isolated just after thermal gelatinization of gran~les.’’~ Little is understood regarding the structure of starch-protein components of granules. It is probable that proteins are a part of lipoprotein membranes of original amyloplasts, or of membrane-bound starch-

406

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

synthesizing systems that operate during membrane de~elopment.~’~ The extent and mode of the interactions between starch and protein contribute to the physical properties of grains. In the case of aged Burley tobacco, Wright et aL980isolated polysaccharides as well as proteins. The mode of separation of both groups of compounds prevents any understanding of whether they existed in tobacco either in the form of a complex or independently of one another. Amylographic studies981on wheat flour in which a natural composition of proteins and the starch-to-protein ratio was perturbed suggested the existence of protein-starch complexes, although, based on the data reported, this conclusion is not fully convincing. More convincing are studies by Sirotkin et ~ 1 . , ~ who * * studied changes in the properties of proteins and the properties of rice flour on storage. It was reported that the solubility of proteins decreased, and the rigidity of gels of rice flour increased, if their original moisture content was 13%. At 15% moisture content, the gels became weaker. A direct correlation has been observed between the number of free disulfide groups in the protein and the decrease in viscosity. A weak tendency toward decreasing the concentration of basic amino acids was observed on storage. A polypeptide complex ( M , 55,000) with cornstarch amylose has been analyzed983;this complex could only be found in amylose-rich starch, and the polypeptide concentration was proportional to the amylose content in the granules. Inside the granule, the polypeptide is bound to amylose via SDS- and D’IT-sensitive linkages. Disruption of these linkages occurs on boiling. This protein is the product of the waxy gene as well as the starch-bound glycosyltransferase.

-

c. Synthetic Complexes.-Many linear natural and synthetic macromolecules tend to assume a helical structure. For example, amylose, cellulose, proteins, and certain synthetic fibers develop this structure and produce the blue reaction in solution with iodine. It is not quite clear what is the role of the Is- ion as a possible driving force for the coiling of such macromolecules. There is also a report that an existing helix induces formation of another helical structure in molecules that are in the vicinity of that helix. These factors and arguments suggest that the formation of synthetic complexes should be considered as the interaction between coils and helices, interactions that are governed by conformational fit. Thermodynamic compatibility of the partners of a complex is another condition which must be accounted for in complex formation. Thermodynamically incompatible components separate into two phases. Tolstoguzov et al.984studied complexes of starch with gelatin in aqueous solutions and showed that complexation requires adjustment of the solution acidity and

COMPLEXES OF STARCH WITH ORGANIC GUESTS

407

Acid concentration FIG.61.-Curves of the viscosimetric titration of the gelatin-o-glucan systems: 1, (1 :l), 2, (2: 1); 3, ( 3 :1). (By permission from Tolstoguzov et ~ 1 . ' ~ )

selection of the starch-to-gelatin ratio (Fig. 61). This figure shows how the viscosity of the system depends on the ratio and solution pH for the gelatin-amylopectin-water system. The dependence of complex formation on acidity is explained as the adjustment of the isoelectric point of a protein in which its self-association vanishes. The pH dependence of interactions of amylopectin with human serum protein has been similarly interpreted.985 Exothermic effects resulting from starch-protein interactions during the blending of starch-protein mixtures are indications of thermodynamic comAs the molecular weight of the co-complexing polymer patibility.yxX"~yx' increases, the role of entropic contributions diminishes considerably.987 L i p a t ~ v suggested ~~' the fundamental role of the starch-to-protein (gelatin) ratio in avoiding phase separation of both components in aqueous dispersions (Fig. 62). This figure illustrates the viscosity as a function of the gelatin-to-starch ratio and the dispersion. The role of temperature in the The phase compatibility of that system was studied by Tolstoguzov el diagram (Fig. 63) shows the high sensitivity of the system to temperature. Grinberg and Tolstoguzovygosummarized the effects of various factors on thermodynamic compatibility in the starch-gelatin-water system and noted that elevated temperatures caused denaturation of the protein. In general, denatured proteins cannot form starch complexes,w1although again it is a matter of the starch variety and the starch-to-protein ratio.992

3 2 2 1 100% Gelatin

50

100 V

O

Starch

FIG.62.-The variation of specific viscosity ( vr) with composition of mixtures of 0.5%aq. solutions of gelatin and dispersed starch. (By permission from Lipatov and Lipatov."=)

408

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

4

8

12

16 20 c1 .o/o

FIG.63.-Phase diagram of the gelatin-colloidal starch-water system I, 45°C; II.35"C; 111. points of initial mechanical mixtures. (Reprinted with permission from V. Ya. Grinberg, V. B. Tolstoguzov, and G. L. Slonimskii, Kolloid. Zh., 33 (1971) 666-669.)

The thermodynamic compatibility of biological and synthetic polymers is a common question."93Beijerin~k,'~~ and Ostwald and Herte1,'95 studied the thermodynamic compatibility of proteins and polysaccharides, and the latter authors evaluated the role of the source of starch. In contrast to cereal starches, potato starch is compatible with proteins in both acidic and basic media, whereas, Dahle991reported that wheat starch sorbs proteins mainly in acidic and neutral solutions. Specific interactions between starch and proteins were observed as early as the beginning of the twentieth century. Berczeller9" noted that the surface tension of aqueous soap solutions did not decrease with the addition of protein (egg albumin) alone, but it did decrease when starch and protein were added. This effect was observed to increase with time. Sorption of albumin on starch is inhibited by bi- and trivalent ions and at the isoelectric point. Below the isoelectric point, bonding between starch and albumin is ionic in character, whereas nonionic interactions are expected above the isoelectric point.997The Terayama hypothesis998predicts the formation of protein complexes with starch, provided that starch exhibits the properties of a polyelectrolyte. Apart from chemically modified anionic starches (such as starch sulfate, starch phosphate, and various cross-linked starch derivatives bearing ionized functions), potato starch is the only variety that behaves as a polyelectrolyte. Its random phosphate ester moieties permit proteins to form complexes with it. Takeuchi ef uL99y-1002demonstrated such a possibility with various proteins and a 4% gel of potato starch. Studies on the complexation of saccharides with gelatin'oo3revealed that the binding ratio for complete binding of soluble starch to gelatin is 0.5 (on a dry-weight basis). Autoclaving does not affect the ability of starch to form a complex with gelatin. The addition of gelatin to corn grits affect

COMPLEXES OF STARCH WITH ORGANIC GUESTS

409

only slightly the torque needed for extrusion. In contrast, agar affects this torque significant1y.lm In order to prove the formation of starch-protein complexes, a synthetic dough was preparedIm5consisting of wheat, potato, and rice starch. Relationships between the dough viscosity, shear modulus, and the specific surface area of different varieties of starch were evaluated, and they indicated that the viscosity and shear modulus increase upon decreasing the granule size and increasing the specific surface area of all varieties of starch except for potato starch. The authors'ws*1006 interpreted these data in terms of the thickness of a hydration layer between starch granules, which plays the role of an active filler of the protein network. Ka~senbeck'~'drew a similar conclusion, based on studies of ultrathin sections of mature wheat kernels, flour, and dough. In mixtures of hard wheat starch and proteins, a three-dimensional network is formed in which strong, local adhesion sites exist between starch surfaces and proteins. Such interactions are only partly broken down in the dough prepared from hard wheat. Such structures do not exist in soft wheat because of the absence of these local adhesion sites. Raising the starch concentration in synthetic dough increases the viscosity and shear modulus.'006~'008 It has been observed1"09that proteins bound to starch sorb more lecithin than unbound, free protein. Complexes of enzymes and starch are documented to a greater extent. In this case the origin of starch can be a critical factor. For instance, isolation of beta amylase is enabled by adsorption on starch. Among the different varieties tested, crude rice starch appeared to be superior with respect to its sorption characteristics, primarly because of its fine grain size.'(''' Complexes of amylases and other enzymes with starch have also been The adsorption of alpha amylase on starch is a reversible process that takes place selectively on spherulites of granules and is inhibited by maltose and malto-oligosaccharides.'012The binding energy if -20.7 kJ/mol.'0'6 This value is approximately one-third less than the binding energy of alpha amylase to soluble amylose (approximately -30 kJ/m~l).'"'~.'"'~ The amount of complexed alpha amylase correlates with the surface area of starch according to the equation S=

M/"Tmaxl,

(13)

where S is the available surface area per enzyme molecule, rmax is the amount of enzyme adsorbed at the state of equilibrium corresponding to the plateau on Fig. 64, and M and N are the molecular weight of the enzyme and Avogadro's number, respectively.''l6 Figure 64 presents the adsorption isotherm of alpha amylase on spherulites at 25°C. It is apparent that the spherulites are rapidly saturated with enzyme at relatively low concentrations of solution. Enzymes complexed on starch do not lose their ability

410

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

0

00150m250300350 0 50 1 Concentration,f i g I mL

FIG.64.-Adsorption isotherm of alpha amylase to spherulites at 25°C. (Reprinted with permission from V. M. Lelong, P. Colonna, and S. G . Ring, Biotechnol. Bioenerg., 38 (1991) 127-134.)

to chelate metal c~mplexes,'"'~ nor do they lose their activity with respect to starch. For beta amylase, the activity is proportional to the adsorption on starch. Complexation stabilizes enzyme activity, as demonstrated for alkaline ph~sphatase.'"'~Pullulanase does not adsorb on ~tarch.'"'~ Ribonucleic acid also forms a complex with ~ t a r ~ hbut, it~ is~rather ~ ~ weak - ~ ~ ~ ~ and dissociates into components when treated with ethanol. The UV absorption maximum of this complex (250 nm) is also the absorption maximum for RNA itself.'"" The complex of RNA with amylose isomerase and starch is more stable; it precipitates in acidic solutions and redissolves in basic ones. Interactions between starch and proteins have some other practical features. For example, soluble starch, amylose, and amylopectin coacervate from aqueous solutions of a highly concentrated gelatin ~01.'"~When this is performed in the presence of chloral hydrate, the resulting coacervate contains both starch and gelatin in vacuolated and adsorbed form.'024 A protein binder for food products which has a high capacity to bind water and high stability on long-term storage after boiling can be prepared from wheat flour, milk proteins, and soybean meal.In2' An edible complex of casein and starch based on sodium caseinate has been patented and is characterized by a high viscosity due to a synergistic effect of both components."'2""028 Sodium caseinate causes swelling of starch particles in suspenion."'^^ The complexation decreases the rate of swelling and prevents swollen granules from collapsing. In addition, egg white can be preserved from freeze damage by the addition of starch, preferably tapioca starch.""" A composition of starch, protein, and water constitutes a patented floccu1ant.In3ICoated paper, suitable for printing, may be prepared by coating it with a starch-soybean protein complex generated in situ on the paper surface.'032 Starch-protein complexes are also patented as additives that increase baking ~ a p a c i t y . ' " ~ ~ - ' " ~ ~

COMPLEXES OF STARCH WITH ORGANIC GUESTS

411

The rheological behavior of systems containing starch, soybean protein, soybean oil, and water (5:10:1040) has been studied."38 The viscosity of the system depends on the origin of the starch. For example, the viscosity of a potato-starch gel markedly decreases upon the addition of protein. In contrast, a cornstarch gel is much more stable and does not show a decrease in viscosity after the addition of protein. The incorporation of proteins into a lipid-starch system shows that proteins are distributed among both components of the system.885 Synthetic complexes of starch with proteins have rather limited applications, in contrast to protein complexes with anionic starches. This problem has been reviewed several times by Tolstoguzov et a1.1039-1041 2. Complexes with Dextrins, Polysaccharide Gums, Alginates, Pectins, and Starch Derivatives

All of the polysaccharide species listed here have been used in the design of adhesives, thickeners, binders, and sizes. Little theoretical work has been performed on these systems. A key problem in the food technology industry is the search for more energy-efficient processing methods. For example, during the extrusion of corn grits, the role of hydrocolloids in decreasing the extruder torque was evaluated.lNMLocust bean, agar agar, guar, alginate, and gum arabic were found to lower the torque at 50"C, but they were ineffective at higher temperatures. In contrast, tragacanth, carrageenan, xanthan, and pectin exhibited no effects at all. Other groups of investigators observed similar effects of alginates on extrusion characteristic^.'^^^^^^^^ Interactions between alginnate and gelatinized starch are rather weak, and it was observed that alginate causes an insignificant increase in the viscosity of the original gel.'040.1w Starch-dextrin compositions have been used for centuries as gl~e.'@'~-'@'' Mixtures with greater adhesive strength have been prepared by adding glycerol,'"4Rkaolin, sodium poIy(methapho~phate),'@'~and Compositions of petrolatum oil, glycerol, and dextrin have been used as an additive in the manufacture of bread.'"51 Strong interactions are postulated between starch and such polysaccharide gums as guar and xanthan. These strong interactions lead to the formation of firm gels.'052A typical composition entails agar plus Starch mixed with such polysaccharide gums as guar, xanthan, and locust bean are used as food thickeners, especially when a surfactant is added.'OS6 A composition of guar gum coated with starch has been patented for decreasing levels of cholesterol and glucose in blood.'0s7 Starch blended with "achrodextrin," gum arabic, and sodium silicate is used as an adhesive for book binding.'"''

412

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

As with agar, pectin has also been used to strengthen starch gels.InSs Earlier reports indicate concentrations of up to 5% of pectin as a useful ingredient in baked food product^,"'^^ but a later paper suggests that pectin is an undesirable component in bread, because it retards firmness and hastens baking.lo'" There are also patents on compositions of starch with modified esterified, etherified, and cross-linked starch to produce sizes'061and adhesive^.'^^^-'"^^

3. Complexes with Cellulose and Modified Cellulose The formation of starch complexes with other polysaccharides is perhaps best evidenced by the sorption of starch on cellulose and its derivatives. This sorption is selective with respect to amylose and amylopectin.'06s.1066 Cotton fibers selectively adsorb amylose and not a r n y l ~ p e c t i n . ' ~ How~~-'~~~ ever, this method cannot be used for starch fractionation because cotton was considered to induce degradation (hydroly~is).'~~ On the other hand, a method of purifying amylopectin that involves sorption of amylose on defatted cellulose has been published.'072Reversible adsorption of amylopectin on cellulose occurs when starch is equilibrated with urea in 32-35% ethanol. There are also published attempts to separate starch components on filter paper.'073-'076The reverse idea is applied in the stabilization of nitrocellulose by its sorption on starch.'077 The interaction of starch with cellulose is attributed to van der Waals forces. The zeta potential of cellulose decreases in contact with starch.ln7* Several reviews have been published on the adsorption of starch on cellulose fibers during papermaking.1079-10w Reports as early as the beginning of this century recommend the addition of 5-6% of starch to cellu10se.'0x5-1088 Many different varieties of starches have been used. For example, L ~ t z " * recommended ~ wheat and corn starches, and Traquarelo9' suggested the use of root starches. Unfortunately, for neutral starch, sorption on cellulose is rather weak. Comparative s t ~ d i e s ' ~ ~revealed ' - ' ~ ~ ~that a retention of only 30% of nonionic starch on cellulose can be achieved, whereas cationic starch exhibits nearly 90% retention. This retention is slightly dependent on the pH and the particle size distribution of the pulp. Various authors reported the strengthening of paper by blending plain starch with cellulose along with such additives as poly(viny1 alcohol), Graham salt and boric acid,loY4colemanite, phosphoric acid, ammonia, paraffin, and formaldehyde-urea copolymer,1095 perlite,lo9' latex and asphalt,'o97polyvinyl chloride, acrylic resins, urethane resins, and p~ly(ethyleneimine),~~~* poly(acrylamide), and ZrOC12.1n99 In some cases, purely physical interactions are involved in making a binder, whereas in others some cross-linking is involved. It is

COMPLEXES OF STARCH WITH ORGANIC GUESTS

413

reported that cationic starches are superior for the paper industry."OO~"O' However, starch complexed with tetralkylammonium salts can also be ~ ~ e d A . renaissance ~ ~ ~ ' has ~ ,been ~ predicted ~ ~ ~ for the application of starch in the paper ind~stry.'"~ Such cellulose derivatives as 0-(carboxymethy1)cellulose (CMC) are blended with starch to form adhesives for corrugated board.'lW It has been reported that CMC decreases the effective viscosity of a starch paste and reduces the yield ~trength."~' Sodium CMC prevents the normal rheological behavior of starch paste, an effect that depends on the degree of etherification."'" Adhesives have also been prepared by combining CMC with starch and other components, including "dextrins,""07 sodium sorbate,"08 guar and/or alginate, and poly(viny1 alcohol)."w Patent also exist on more complicated adhesive combinations with 2-hydroxyethylcellulose,vinyl acetatemaleic anhydride copolymer, glyoxal, and borax,"" as well as (Zhydroxypropy1)methylcellulose with poly(viny1 chloride).""

4. Complexes with Synthetic Polymers Poly(viny1 alcohol) is utilized as a component of starch-based adhesives.1112-"'40 t her patents report the use of partially oxidized starch,'"' dextrins,"16dextrins and urea,1117 borax,"I8 boric and vinyl methyl ether-maleic acid copolymers.'12' Other patents indicate the use of poly (vinyl alcohol) with partially hydrolyzed poly(viny1 acetate),lI2' nonhydrolyzed poly(viny1 acetate),1122 and poly(viny1 chloride)."23 A few patents have reported such polyacrylic additives as poly(acry1ic and its salts,"25 p~ly(acrylamide),'~~~~''~~ N-methylacrylamide or poly(N-acrylamide),"28 and p~lyethyleneimine."~~ Polystyrene has also been used,"30 as well as more complex copolymers such as a maleic acid monobutyl ester-methyl vinyl ether copolymer, together with dextrin and poly(acry1amide),'13' carboxylated ethyl acrylate-styrene zinc salt c ~ p o l y m e r , "eth~~ ylene-methyl acrylate-vinyl acetate copolymer,'133vinyl acetate-vinyl pyrrolidone and ethylene-vinyl acetate c o p ~ l y m e r . "Some ~~ adhesives are compounded with SBR 1 a t e ~ and ~ ~phenol-formal~ ~ - ~ ~ ~ ~ dehyde resins.1139 Since several synthetic polymers also develop a blue color upon reaction with iodine, it is likely that they have a helical structure similar to that of amylose. Therefore it is probable that the aforementioned complexes of synthetic polymers with starch can exist in the form of a double helix. ACKNOWLEDGMENT The authors wish to thank the Office of Basic Energy Sciences at the U. S. Department of Energy for supporting this research.

414

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

REFERENCES (649) Hegnauer, Chemoruxonomie der pfunzen, Birkhause Verlag, Basel, Vol. 11 (1967) 467-477; VOI. VII (1980) 609-618. (650) K. D. Goebel and D. A. Brant, Macromolecules 3 (1970) 644-654. (651) C. V. Goebel, W. L. Dimpfl and D. A. Brant, Macromolecules 3 (1970) 644-654. (652) D. A. Brant and W. L. Dimpfl, Macromolecules 3 (1970) 655-664. (653) W. J. James, D. French and R. E. Rundle, Acru Crysrullogr., 12 (1959) 385-389. (654) T. Kuge and K. Takeo, Agr. Biol. Chem. Tokyo, 31 (1967) 257-258. (655) H. Suzuki and N. Taguchi, Asuhi Gurusu Kogyo Gijutsu Shoreikun, 36 (1980) 31 1-321; Chem. Abstr., 94 (1981) 209108b. (656) F. Osman-Ismail and J. S o h , Stuerke 24 (1972) 213-216. (657) D. French, A. 0. Pulley, and W. J. Whelan, Stuerke, 15 (1963) 349-354. (658) F. Osman-lsmail and F. Solms, Lebensm. Wiss. Technol., 6 (1973) 147-150. (659) M. Ulmann and F. Schierbaum, Stuerke, 11 (1959) 203-212. (660) G. Scatchard, Ann N.Y. Acud. Sci., 15 (1949) 660-672. (661) H. Suzuki, T. Amakai, and H. Ogino, Wusedu Daiguku Rikoguku Kenkyusho Hokoku, (92) (1980) 116-117. (662) 0. D. Kurilenko and E. A. Yakovkina, Kolloid. Zh., 22 (1960) 282-286. (663) H. N. Barham and C. L. Campbell, Trans. Kansas Acud. Sci., 53 (1950) 235-253. (664) S. Schwimmer and A. K. Balls, J. Biol. Chem., 180 (1949) 883-894. (665) W. K. Kirkpatrick, U.S. Pat. 2,568,742 (1952); Chem. Absrr., 46 (1952) 1243. (666) S. J. Przylecki and R. Majmin, Biochem. Z., 271 (1934) 168-173. (667) B. Jorgenson, Kolloid Beih., 44 (1936) 285-286. (668) Gesellschaft fuer Industrieforschungen und Betriebsversuche, Swiss Pat. 230,897 (1944); Chem. Absrr., 43 (1949) 3117. (669) M. Schlenk, D. M. Sand, and J. A. Tilloton, US Pat. 2,827,452 (1958); Chem. Absrr., 52 (1958) 12901~. (670) Deutsche Hydrierwerke A.-G., British Pat. 475,809 (1937); Chem. Abstr., 32 (1938) 3863. (671) K. M. Gaver, U S . Pat. 2,389,771 (1945); Chem. Absrr., 40 (1946) 1035. (672) A. M. Altschul and L. E. Costillon, U S . Pat. 2,563,808 (1951); Chem. Absrr., 45 (1951) 9227. (673) T. Kuge and K. Takeo Agr. Boil Chem., 32 (1968) 1232-1238. (674) H. G . Maier and A. Bauer, Stuerke, 24 (1972) 101-107. (675) K. Duckova and M. Mandak, Phurmuzie, 36 (1981) 634-635. (676) Z. Horowicz, Biochem. Z., 257 (1933) 344-350. (677) M. Gibinski, M. Palasinski, and P. Tomasik, Stuerke 45 (1993) 354-357. (678) M. Baczkowicz, M. Sikora, P. Tomasik, and W. Zawadzki, Stuerke, 43 (1991) 294-299. (679) R. Wyler and J. Solms, Lebensm. Wiss. Techno/., 14 (1981) 296-300. (680) J. Solms, F. Osman-Ismail, and M. Beyler, Can. Inst. Food Sci. Technol. J., (1973) AlO-A16. (681) F. Schierbaum, Nuhrung, 3 (1959) 102-116. (682) M. Ulmann and F. Schierbaum, Kolloid-Z., 156 (1958) 156-157. (683) M. Baczkowicz and P. Tomasik, Stuerke, 41 (1989) 449-452. (684) M. Baczkowicz and P. Tomasik. Acta Aliment. Pol. 17 (1991) 269-274. (685) Jay-lin Jane and J. F. Robyt, Curbohydr. Rex, 132 (1984) 105-118. (686) W. Bushuk and C. A. Winkler, Cereal Chem., 34 (1957) 87-93. (687) R. L. Whistler and G. E. Hilbert, J. Am. Chem. SOC.,67 (1945) 1161-1165. (688) R. B. Hass and E. F. Riley, Chem. Revs., 32 (1943) 373-430 (1990) 307-309.

COMPLEXES OF STARCH WITH ORGANIC GUESTS

415

M. Federowicz, M. Palasinski, and P. Tomasik, Sfuerke, 34 (1982) 413-421. S. R. Erlander and R. Tobin. Mucromol. Chem., 111 (1968) 194-211. D. Klimek, S. Poliszko, and M. Pyda, Acfa Aliment. Pol., 17 (1991) 403-409. M. V. Chapek, Kolloid. Zh., 4 (1938) 123-130. J. P. Crawshaw and J. P. Hills, Ind. Eng. Chem. Res., 29 (1990) 307-309. A. V. Dumanskii, Ya. F. Mezhennyi, and E. F. Nekryach, Kolloid Zh., 10 (1948) 103-111. (695) 0.A. Dumanskii, N. N. Kostenyuk, and V. M. Chegoryan, Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol., 18 (1975) 330. (696) W. Maciejewska and M. Kaczmarski, J. Ruman Spectr., 20 (1989) 413-418. (697) H. M. Baranowska and W. Maciejewska, Acfu Alimenf. Pol., 17 (1991) 301-307. (698) E. Weigel. Kolloid-Z., 102 (1943) 145-154. (699) T. J. Schoch, J. Am. Chem. SOC.,64 (1942) 2957-2961. (700) W. J. Katzbeck and R. W. Kerr, J. Am. Chem. Soc., 72 (1950) 3208-3211. (701) R. W. Kerr, 0. R. Trubell, and G. M. Severson, Cereal Chem., 19 (1942) 64-81. (702) R. W. Kerr and G. M. Severson, J. Am. Chem. Soc., 65 (1943) 93-98. (703) J. M. G. Cowie and C. T. Greenwood, J. Chem. SOC.,(1957) 4640-4644. (704) E. M. Montgomery and K. R. Sexson, U S . Pat. 3,046,161 (1962); Chem. Absrr., 57 (1962) 11440. (705) T. J. Schoch, in J. A. Radley (Ed) Sfurch and Ifs Derivatives, Chapman Hill, London, 1953, Vol. 1, p. 123. (706) K. H. Meyer and P. Rathgeb, Helv. Chim. Acru, 31 (1948) 1533-1536. (707) R. S. Bear, J. Am. Chem. SOC., 66 (1944) 2122-2123. (708) H. F. Zobel, Methods Curbohydr. Chem., 4 (1964) 109-114. (709) J. Hollo, J. Szejtli, E. Laszlo, G. S. Gautner, and M. Toth, Sfuerke, 12 (1960) 287-295. (710) H. Suzuki, S. Akimoto, and S. Kamogawa, Denpun Kaguku, 24 (1977) 112-119; Chem. Absrr.. 91 (1979) 122271~. (711) T. Kagitani, M. Minagawa, Y. Nakahara, R. Kimura, T. Tsubakimoto, R. Oshiuni, and K. Sakano, Jpn. Kokui Tokkyo Koho JP 61 115,020 (1986); Chem. Absfr., 105 (1986) 203192~. (712) T. J. McCarthy, J. Mond. Pharm., 12 (1969) 321-329. (713) M. Rohmer, G. Ourisson, and R. G. Brandt, Eur. J. Biochem., 31 (1972) 172-179. (714) 0. J. Pollak, J. Am. Geriatric SOC.,9 (1961) 349-358. (715) H. Zeitlin. N. Kondo, and W. Jordan, J. Phys. Chem. Solids, 25 (1964) 641-644. (716) K. Takahashi and Y. Torii, Yukagaku Zasshi, (1969) 538-43; Chem. Abstr., 71 (1969) 3338111. (717) M. A. Rutschmann and J. Solms, Lebensm. Wiss. Technol., 23 (1990) 70-79. (718) J. F. Kennedy and M. F. Chaplin, British Pat. 1,560,938 (1980); Chem. Absrr., 93 (1980) 72923~. (719) J. J. Blanksma, Red. Trav. Chim. Pays-Bus, 48 (1929) 351-360. (720) J. A. Radley, Sfurch and Its Derivafives, Chapman & Hill, London, 4th ed., 1968, pp. 388-391. (721) H. J. Roberts in R. L. Whistler and E. E. Paschal1 (Eds.), vol. 2, Academic Press, New York, 1967, p. 330. (722) K. H. Meyer, W. Brentano, and P. Bernfeld, Helv. Chim. Acru, 24 (1941) 845-853. (723) K. H. Meyer, P. Bernfeld, and E. Wolff, Helv. Chim. Acru, 24 (1941) 854-864. (723a) H. Suzuki, H. Amakai, and H. Ogino, Denpun Kaguku, 28 (1981) 245-250; Chem. Absfr. 96 (1982) 143205~. (724) R. Rutgers, J. Sci. Food Agr., 6 (1955) 735-738. (689) (690) (691) (692) (693) (694)

416

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

(725) M. A. Rutschmann, J. Heininger, V. Pliska, and J. S o h , Lebensrn. Wiss. Technol., 22 (1989) 240-244. (726) K. Takeo and T. Kuge, Agric. Biol. Chem. Tokyo, 35 (1971) 537-542. (727) V. D. Canic and N. Perisic-Janjic, Techniku (Belgrade), 25 (1970) 330-332. (728) S. Moore and W. H. Stein, Ann. N. Y.Acud. Sci., 49 (1948) 265-278. (729) C. Chinball, Brit. Med. Bull., 10 (1954) 183-186. (730) E. Soto Figueroa and F. B. Seibert, Proc. SOC. Expfl. Biol. Med., 83 (1953) 535-537. (731) B. Lindquist and T. Storgors, Nature, 175 (1955) 511-512. (732) S. M. Petrovic and S. E. Petrovic, J. Chromufogr., 21 (1966) 313-317. (733) V. Canic and J. Petrovic, Hem. fnd., 27 (1973) HI73-HI76. (734) H. Krebs, J. Diewald, and J. A. Wagner, Angew. Chem., 67 (1955) 705. (735) M. Ohara, K. Ohta and F. Kwan, Bull. Chem. SOC. Jpn., 37 (1964) 76-79. (736) A. Lesnitzky and L. F. Loeb, Biochem. Z., 146 (1924) 96-107. (737) L. Lehrman, J. Am. Chem. Soc., 51 (1929) 2185-2188. (738) L. Lehrman, J. Am. Chem. Soc., 64 (1934) 212-213. (739) L. Lehrman, J. Am. Chem. Soc., 64 (1942) 2144-2146. (740) S. Furukawa, K. Oba, and T. Fuji, Denpun Kogyo Gukkuishi, 13 (1966) 75-81; Chem. Absfr., 66 (1967) 3019311. (741) K. Yasunatsu and S. Moritaka, J. Food Sci., 29 (1964) 198-202. (742) T. C. Taylor and J. M. Nelson, J. Am. Chem. Soc., 42 (1920) 1726-1738. (743) J. H. C. Merckel, Kolloid-Beih., 45 (1937) 413-470. (744) W. A. Mitchell and E. Zillmann, Trans. Am. Assoc. Cereal Chemists, 9 (1951) 64-79. (745) Sugiyama Industrial Chemical Institute, Jpn. Kokui Tokkyo Koho, 80,145,526 (1980); Chem. Abstr., 94 (1981) 86074~. (746) L. Acker and G. Brauner-Glaesner, Getreide, Mehl, Brot, 36 (1982) 291-295. (747) V. M. Gray and T. J. Schoch, Stuerke, 14 (1962) 239-246. (748) F. Meuser, B. van Lengerich, and J. Stender, Getreide, Mehl, Brot, 39 (1985) 309-314. (749) R. Meuser, B. van Lengerich, and J. Stender, Getreide, Mehl, Bror, 39 (1985) 205-211. (750) T. J. Schoch, J. Am. Chem. SOC.,60 (1938) 2824-2825. (751) T. J. Schoch and C. B. Williams, J. Am. Chem. Soc., 66 (1944) 1232-1233. (752) F. F. Mikus, R. M. Hixon, and R. E. Rundle,J. Am. Chern. SOC.,68 (1946) 1115-1121. (753) J. Szejtli and E. Banky-Eloed, Sfuerke, 27 (1975) 368-376. (754) K. Takeo, A. Tokumura, and T. Kuge, Stuerke, 25 (1973) 357-362. (755) P. Tomasik, Y. J. Wang, and J. Jane, Sfuerke, 47 (1995) 185-189. (756) W. R. Harrison, J. Sci. Food Agric., 29 (1978) 365-371. (757) S. Tani, Yukuguku Zusshi, 96 (1976) 648-52; Chern. Abstr., 88 (1978) 26611. (758) N. Perisic-Janjic, V. Canic, S. Lomic, and D. Bajkin, Fresenius Z. Anal. Chem., 295 (1979) 263-265. (759) Y. Kadera, Pluegers Arch. Ges. Physiol., 219 (1928) 686-693. (760) A. Reychler, Bull. SOC. Chim. Belg., 23 (1910) 378-383. (761) D. Yamamoto and R. Iwaki, J. Chem. Phys., 19 (1951) 662-667. (762) M. J. Holmes, French Put. M 5,607 (1968); Chem. Abstr., 71 (1969) 42272m. (763) K. Hess and F. A. Smith, Ber., 61 (1928) 1975-1982. (764) K. Hess and F. A. Smith, Ber., 62 (1929) 1619-1626. (765) K. Hess, R. Pfleger, and C. Trogus, Ber., 66 (1933) 1504-1512. (766) F. Schierbaum and K. Taeufel, Stuerke, 15 (1963) 93-98. (767) C. Reschko and J. Hartmann, Nuturwissenschuften, 22 (1934) 451-452. (768) R. S. Higginbotham and G. A. Morrison, Shirley Insf. Mem., 22 (1948) 141-147. (769) A. Sroczynski, W. Iwanowski, and E. Nebesny, Acfu Aliment. Pol., 11 (1985) 3-10. (770) J. Hollo, L. Fodor, and S. Gal, Sfuerke, 31 (1979) 303-306.

COMPLEXES O F STARCH WITH ORGANIC GUESTS

417

(771) N. A. Brukhyanova, Sovremennye Voprosi Vitaminologii, Izdat Medgiz, Moscow, 1955, p. 15-29; Ref: Zh., Khim. Biol. Khim., (1957) 13812. (772) N. N. Berezovskaya, S. M. Bessonov, and Z. V. Kochetkova, Vopr. Pit., 17(4) (1958) 61-65. (773) T. Fukuda, K. Suzuki, J. Hibara, K. Kimura, and H. Masuyama, Shokuhin Eisigaku Zasshi, 5 (1964) 383-90; Chem. Abstr., 62 (1965) 16873. (774) Y. Yang and G. K. Yin, Yaoxue Xuebao 23 (1988) 152-158 Chem. Abstr., 108 (1989) 210083d. (775) K . Okumura and A. Hayakawa, Bitamin, 23 (1961) 333-336. (776) S. Saito, Kolloid-Z., 154 (1957) 19-29. (777) M. Yamamoto, S. Harada, T. Sano, T. Yasunaga, and N . Tatsumoto, Biopolymers, 23 (1984) 2083-2096. (778) I. D. Evans, Staerke, 38 (1986) 227-235. (779) M. Yenson, Rev. Fac. Sci. Univ. Istanbul. 13A (1948) 97-101. (780) K. M. Gaver, U S . Pat. 2,735,821 (1956); Chem. Abstr., 50 (1956) 9046. (781) C. Naegli, Bot. Zrg., 39 (1881) 633-655. (782) H. Fischer, Beih. Bot. Zentrbl. Abt. A., 12 (1902) 226-242. (783) H. Fischer, Beih. Bot. Zentrbl. Abt. A., 18 (1905) 409-432. (784) H. Kramer, Bot. Gazz. (Chicago), 34 (1902) 341-354. (785) R. H. Denniston, Trans. Wisconsin Acad. Sci. Arts and Lett., 14 (1903) 527-533. (786) J. H. Salter, Jahrb. Wiss. Bot., 32 (1898) 117-166. (787) E. T. Reichert, Science, 40 (1914) 649-661. (788) M. Covello, Quad. Nutriz., 4 (1937) 467-474. (789) W. Suida, Sitzber. Akad. Wiss. Wien, Kl. Math.-Naturwiss., Abt. II, 113 (1904) 625-661. (790) W. Suida, Monatsh., 35 (1904) 1107-1143. (791) J. J. L. Zwikker, Recl. Trav. Both. Nerherl., 18 (1921) 1-102. (792) B. Rassow and M. Lobenstein, Kolloid Beih., 33 (1931) 179-253. (793) A. P. Schulz and G. Steinhoff, 2. Spiritusind., 55 (1932) 162. (794) E. Homberger, Ph.D. Theses, Geneva, 1940; J. Seidemann, Staerke Atfas, Paul Parey, Berlin, 1966, p. 26. (795) J. Seidemann, Staerke, 14 (1962) 348-355. (796) J. Huebner and K. Venkataraman, J. SOC. Dyers Colourists, 42 (1926) 110-121. (797) N. Kobamoto, Rykyu Daigaku Nogakubo Gakujutsu Hokoku, (27) (1980) 139-147; Chem. Abstr., 95 (1981) 78619q. (798) S. Lipatov, 2. Anorg. Allgem. Chem., 157 (1926) 22-26. (799) N. Kaneniwa and I . Moriguchi, Yakuzaigaku, 27 (1967) 238-42; Chem. Abstr., 69 (1968) 80588k. (800) V. I. Nazarov and T. I. Sukhorukova, Kolloid. Zh., 25 (1963) 578-580. (801) A. L. Thakkar, W. L. Wilham, and G. Zografi, J. Pharm. Sci., 59 (1970) 1466-1470. (802) G. Zografi and A. M. N. Mattocks, J. Pharm. Sci., 52 (1963) 1103-1105. (803) T. J. Schoch and E. C. Meinwald, Anal. Chem., 28 (1956) 382-387. (804) J. Hofstee, Staerke, 11 (1959) 200-203. (805) E. Bancher and J. Washnuettl, Ber. Deutsch. Bot. Ges., 81 (1968) 169-175. (806) G. Tomita and H . Takeyama, Kagaku (Tokyo), 28 (1958) 308-310. (807) P. Tomasik and W. Zawadzki, Zywn. Technol. Jakosc., 2/7, Suppl., (1996) 51-56. (808) A. T. Czaja, Staerke, 17 (1956) 69-74. (809) N. P. Badenhuizen, Staerke, 17 (1965) 69-74. (810) N. P. Badenhuizen, Staerke, 29 (1977) 109-114. (811) H. E. Sutton and G. W. Karp, Biochem. Biophys. Acta. 107 (1965) 153-154. (812) J. R. Katz and A. Weidinger, 2. Physik. Chem., A168 (1934) 321-323.

418

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

(813) Y. Suda and T. Shirota, Sen-i Gakkaishi, 17 (1961) 414-420; Chem. Abstr., 55 (1961) 17014. (814) Courtaults Ltd., British Pat. 977,586 (1964); Chem. Abstr., 62 (1965) 7930. (815) M. Ono and Y. Sudo, Jpn Kokai Tokkyo Koho JP 01,137,998 (1989); Chem. Abstr., 112 (1990) 51758s. (816) G . Konrad and H. Musso, Chem. Ber., 117 (1984) 423-426. (817) C. N. Rabold, Proc. Am. Assoc. Textile Chem. Colourists, (1935); 247-250; Chem. Abstr., 29 (1935) 6064. (818) K. Polewski and W. Maciejewska, Acta Aliment. POL, 17 (1991) 345-350. (819) M. K. Pal and A. Roy, Makromol. Chem., Rapid Commun., 6 (1985) 749-754. (820) L. G. Dubina, N. L. Kuznetsova, L. I. Khomutov, and E. P. Korchagina, Vysokomol. Soed., Ser. B, 14 (1972) 13-17. (821) M. J. Fishwick and A. J. Wright, Phytochem., 19 (1980) 55-59. (822) W. R. Morrison and T. P. Milligan, Maize: Recent Progress in Chemistry and Technology, (ed. G . E. Inglett), Academic Press, New York, 1982, pp. 1-18. (823) H. P. Wehrli and Y. Pomeranz, Cereal Chem., 47 (1970) 160-166. (824) R. L. Whistler and G. E. Hilbert, J. Am. Chem. SOC., 66 (1944) 1721-1722. (825) W. R. Morrison, Staerke, 33 (1981) 408-410. (826) K. Lorenz, J. Food Sci., 41 (1976) 1357-1359. (827) T. Watanabe, Shokuhin Kogyo, 14 (1971) 105-111; Chem. Abstr., (1972) 57773~. (828) L. Acker, Z. Ernaehrungswiss. Suppl., 16 (1973) 126-135. (829) L. Acker, Getreide, Mehl, Brot, 28 (1974) 181-187. (830) L. Acker, Fett, Seifen, Anstrichm., 79 (1977) 1-9. (831) W. R. Morrison, J. Sci. Food Agric., 29 (1978) 365-367. (832) T. Gaillard, Recent Adv. Phytochem., 17 (1983) 111-136. (833) D. Baisted, Lipids Cereal Technol. (1983) 93-140. (834) F. E. Nottbohm and F. Mayer. Z. Unters. Lebensm., 67 (1934) 369. (835) G. Becker and L. Acker, Staerke, 23 (1971) 339-343. (836) H. Schmitz and L. Acker, Staerke, 19 (1967) 17-21. (837) K. Yasumatsu and S. Moritaka, Agr. Biol. Chem., 28 (1964) 257-264. (838) M. Azudin and W. R. Morrison, J. Cereal Sci., 4 (1986) 23-31. (839) A. Fricker and W. D. Koller, Fette, Seifen, Anstrichm., 74 (1974) 466-469. (840) Y. Hibi andT. Kuge, Denpun Kagaku, 34 (1987) 271-8; Chem. Abstr., 109 (1988) 5392h. (841) P. Bowler, M. R. Williams, and R. E. Angold, Staerke, 32 (1980) 186-189. (842) M. R. Williams and P. Bowler, Staerke, 34 (1982) 221-223. (843) P. Meredith, W. R. Morrison, and H. N. Dengate, Staerke, 30 (1978) 119-125. (844) A. Nakamura, R. Shimizu, T. Kano, and S. Fumakashi, Bull. Agr. Chem. SOC.Jpn., 22 (1958) 324-329. (845) G. Becker and L. Acker, Fette, Seifen, Anstrichm., 76 (1974) 464-466. (846) Y. Hibi, S. Kitamura, and T. Kuge, Cereal Chem., 67 (1990) 7-10. (847) T. G . Hanna and J. Lelievre, Cereal Chem., 52 (1975) 697-701. (848) N. Krog, Staerke, 23 (1971) 206-10. (849) H. N. Dunning and E. H. Borochoft, US Pat. 3,596,666 (1971); Chem. Abstr., 75 (1971) 128683r. (850) E. M. Osman, S. J. Leith, and M. Fles, Cereal Chem., 38 (1961) 449-463. (851) R. Hoover and D. Hadzijev, Staerke, 33 (1981) 346-355. (852) G. Y. Brokaw, Can. Food Ind., 33(4) (1962) 36-39. (853) N. Krog and B. N. Jensen, J. Food Technol., 5 (1970) 77-87. (854) I. Masuyama and T. Oda, Jpn Kokai Tokkyo Koho J p 60,214,845 (1985); Chem. Absrr., 104 (1986) 128632r.

COMPLEXES O F STARCH WITH ORGANIC GUESTS

419

(855) C. Mercier, R. Charbonniere, J. Grebaut, and J. F. de la Gueriviere, Cereal Chem., 57 (1980) 4-9. (856) W. A. Mitchell, W. C. Seidell, and J. D. O’Rurke, European Pat. Appl. 11,479 (1980); Chem. Absfr., 93 (1980) 130970d. (857) F. Meuser, B. van Lengerich, and J. Stender, Veroefl Arbeitsgem. Gefreideforsch., Proc. Ber. Tag. Getreidechem., 35th, (1984) 151-178. (858) Y. J. Kim and R. J. Robinson, Sraerke, 31 (1979) 293-300. (859) T. G. Carlson, K. Larson, N. Dinh-Nguyen, and N. Krog, Staerke, 31 (1979) 22-24. (860) G. Lehmann and H. Gottschield, Fefte, Seifen, Anstrichm., 85 (1983) 439-443. (861) M. Kugimiya, J. W. Donovan, and R. Y . Wong, Staerke, 32 (1980) 265-270. (861a) M. Kugimiya and J. W. Donovan, J. Food Sci. 46 (1981) 765-777. (861b) D. Sievert and Y. Holm, Sfaerke, 45 (1993) 136-139. (862) R. Hoover and D. Hadzijev, Staerke, 33 (1981) 290-300. (863) H. 0. Kim and R. D. Hill, Progr. Biotechnol., 1 (1985) 81-88. (864) N. Krog, Staerke, 25 (1973) 22-27. (865) H. van Lonkhuysen and J. Blankestijn, Sfaerke, 26 (1974) 337-342. (866) A. C. Eliasson, Fats (Lipids) Baking Extrusion Contrib. LIPIDFORUM Symp. 1983, (1984) 50-1; Chem. Abstr., 101 (1984) 12888411. (867) N. Krog, J. Am. Oil Chem. SOC.,54 (1977) 124-131. (868) E. M. Osman, J. Food Technol., 29 (1975) 30-44. (869) E. J. Strandine, G. T. Carlin, G. A. Werner, and R. D. Hoper, Cereal Chem., 28 (1951) 449-462. (870) T. J. Schoch, Bakers’ Dig., 39 (Apr.) (1965) 48-57. (871) C. W. Ofelt, M.M. MacMaster, E. B. Lancaster, and F. R. Senti, Cereal Chem., 35 (1958) 137-141. (872) C. W. Ofelt, C. L. Mehltretter, F. H. Otey, and F. R. Senti, Cereal Chem., 35 (1958) 142-145. (873) G. Jongh, Cereal Chem., 38 (1961) 140-152. (874) T. J. Schoch and D. French, Cereal Chem., 24 (1947) 231-249. (875) S. A. Watson, R. L. Whistler, and G. H. Hilbert, cited after W. F. Geddes and C. W. Bice in The Role of Starch in Bread Staling, Quartermaster Corps. Rept. QMC 17-10. Quartermaster General, Washington, D.C. (1964). (876) K. Ohashi, G. Goshima, K. Kusuda, and H. Tsuge, Sraerke, 32 (1980) 54-58. (877) W. R. Morrison and M. N. Azudin, J. Cereal Sci., 5 (1987) 35-44. (878) R. Germani, C. F. Ciacco, and D. B. Rodriguez Amaya, Staerke, 35 (1983) 377-381. (879) W. H. Knightly, Proc. 47th Annu. Meeting ACCC, 1962, cited after pos. 226. (880) J. Lagendijk and H. J. Pennings, Cereal Sci. Today, 15 (1970) 354-365. (881) W. Seibel, A. Menger, G. Hampel, and H. Stephan, Brot, Gebaeck, 22 (1968) 193-202. (882) J. C. Wootton, N. B. Howard, J. B. Martin, D. E. McOskar, and J. Holme, Cereal Chem., 44 (1967) 333-343. (883) K. Larsson, K. Gabrielsson, and B. Lundberg, J. Sci. Food Agric., 29 (1978) 909-914. (884) E. J. Bourne, A. J. Tiffin, and H. Weigel, J. Sci. Food Agric., 11 (1960) 101-109. (885) R. R. Baldwin, S. T. Titcomb, R. G. Johansen, W. J. Keogh, and D. Koedding, Cereal Sci. Today, 10 (1965) 452,454,456-457. (886) P. Meredith, New Zealand J. Sci., 4 (1961) 66-77. (887) A. C. Eliasson, H. Finstad, and G. Ljunger, Staerke, 40 (1988) 95-100. (888) Z. Mori, Agric. Biol. Chem., 44 (1980) 1455-1459. (889) H. Toguchi, M. Yamanaka, K. Iga, and T. Shimamoto, Japan Kokai, 76 35,415 (1976); Chem. Absfr., 85 (1976) 51748n.

420

PlOTR TOMASIK AND CHRISTOPHER H. SCHILLING

(890) F. Wittwer and J. Tomka, German Par. DE 3,712,029 (1987); Chem. Absrr., 108 (1988) 52287~. (891) N. V. W. A. Scholten’s Chemische Fabriken, British Pat. 483,037 (1938); Chem. Absrr., 32 (1938) 7164. (892) N. V. W. A. Scholten’s Chemische Fabriken, French Par. 811,598(1937); Chem. Absrr., 32 (1938) 683. (893) G. Galosi and P. Horvat, Hungarian Pat. 34,231(1985); Chem. Absrr., 103 (985) 72168d. (894) J. Holm, J. Bjoerck, S. Ostrowska, A X . Eliasson, N.-G. Asp, K. Larsson and I. Lundquist. Staerke, 35 (1983) 294-297. (895) J. Holm, S . Ostrowska, N.-G. Asp, J. Bjoerck, K. Larsson, and I. Lundquist, Suppl. Naeringsforsk., 20 (1984) 42-43. (896) K. Larsson and Y. Miezis, Sraerke, 31 (1979) 301-302. (897) A. Menger, Getreide, Mehl, Brot, 28 (1971) 301-304. (898) J. L. Robinson, J. A. G. Weinert, and J. S o h , Lebensm. Wiss. Technol., 16 (1983) 235-238. (899) J. L. Robinson and J. Solms, Lebensm. Wiss. Technol., 17 (1984) 290-292. (900) A. Pasternack and U. H. Stenman, Clin. Chem. Acta. 65 (1975) 213-221. (901) L. Berczeller, Biochem. Z., 90 (1918) 290-293. (902) W. A. Harris, L. W. Norman, J. H. Turner, H. F. Haney, and R.H. Cotton, Ind. Eng. Chem., 44 (1952) 2414-2417. (903) S . Zagrodzki and Z. Niedzielski, Ind. Aliment. Agr., 85 (1968) 999-1002. (904) L. Maczelka, Elelmezesi Ipar. 10 (1956) 231-9; Food Sci. Absrr., 29 (1957) Abstr. No. 2622. (905) G. Malfitano and A. Moschkoff, C. R. Acad. Sci., 156 (1913) 142-145. (906) A. V. Zubchenkoand A. Ya. Oleinikova, Izv. Vyssh. Uchebn. Zaved., fishch. Tekhnol., (1) (1975) 115-116. (907) A. B. Rizzuto, A. C. Chen, and M. F. Veiga, Pharm. Technol., 8 (9) (1984) 32, 34, 36, 38-39. (908) S. Woodruff and L. Nicoli, Cereal Chem., 8 (1931) 243-251. (909) R. Germani, C. F. Ciacco, and D. B. Rodriguez-Amaya, Staerke, 35 (1983) 377-381. (910) K. J. L’Anson, M. J. Miles, V. J. Morris, L. S . Besford, D. A. Jarvis, and R. A. Marsh, 1. Cereal Sci., 11 (1990) 243-248. (911) S . K.Kim and B. L. D’Appolonia, Cereal Chem., 54 (1977) 150-160. (912) V. F. Rasper and B. MacDonald, Baker’s Dig., 50(12) (1967) 47. (913) J. Cerning-Beroard and A. Guilbot, Bull. Anc. Eleves E. Meun. ENSMIC 28 (1978) 79-87; Chem. Absrr., 89 (1978) 22345f. (914) J. Casier, German Pat. 2,047,504 (1971); Chem. Absrr. 75 (1971) 117359~. (915) J. F. Chu and F. C. Chu, Taiwan Sugar, 8 (1961) 18-23; Chem. Absrr., 58 (1963) 7019. (916) G. M. Elgal, Proc. Sugar Process. Res. Con$, 1981. (1983) 104-118 Chern. Absrr.. 99 (1983) 7100k. (917) P. Hidi and R. J. McCowage, Proc. Sugar Process. Res. Cant, 1984, (1986) 186-208; Chem. Absrr., 105 (1986) 174732k. (918) J. A. Devereaux and M. A. Clarke, Proc. Sugar Process. Res. Con$, 1984. (1986) 209-230; Chem. Abstr., 105 (1986) 174717r. (919) M. Kapp, Proc. Cuisson Con$, 1966, (1967) 85-103; Chem. Absrr., 72 (1970) 7760411. (920) P. M. Arkhangelskii, I. A. Kalashnikov, and V. S. Gryuner, Sakh. from., 41(9) (1967) 50-53. (921) M. L. Bean and E. M. Osman, Food Res., 24 (1959) 665-671. (922) E. F. Hester, A. M. Briant, and C. J. Personius, Cereal Chem., 33 (1956) 91-101. (923) J. L. Maxwel and H. F. Zobel, Cereal Food World, 23 (1978) 124-128.

COMPLEXES O F STARCH WITH ORGANIC GUESTS

421

S. Woodruff and M. MacMasters, Trans. Ill. State Acad. Sci., 29 (1936) 107-109. P. Chinachoti, Food Technol., (1933) 134-140. J. Jane and P. Tomasik, personal communication. A. Chungcharoen and D. B. Lund, Cereal Chem., 64 (1987) 240-243. M. Kugimiya and H. Sakai, Hiroshima-Ken Shokukin Kogyo Shikenyo Kenkyu Hokoku, 13 (1974) 19-23; Chem. Abstr., 84 (1976) 57526q. (929) R. T. Whittenberger and G. C . Nutting, Ind. Eng. Chem., 40 (1948) 1407-1413. (930) R. L. Cheer and J. Lelievere, J. Appl. Polym. Sci., 28 (1983) 1829-1837. (931) K. Taeufel and F. Berschneider, Nahrung, 2 (1958) 683-696. (932) K. Taeufel. G. Feldmann, and W. Panzer, Natunvissenschafien 43 (1956) 374-375. (933) B. L. D’Appolonia, Cereal Chem., 49 (1972) 532-543. (934) M. L. Bean and W. T. Yamazaki, Cereal Chem., 55 (1978) 936-944. (935) H. L. Savage and E. M. Osman, Cereal Chem., 55 (1978) 447-454. (936) K. W. Lang and M. P. Steinberg, J. Food Sci., 45 (1980) 1228-1236. (937) P. Chinachoti and M. P. Steinberg, J . Food Sci., 49 (1984) 1604-1608. (938) P. J. Carillo, S. G. Gilbert, and H. Daun, J. Food Sci., 53 (1988) 1199-203. (939) P. J. Carillo, S. G. Gilbert, and H. Daun, J. Food Sci., 54 (1989) 162-165. (940) S. J. Richardson, I. C. Baianu, and M. P. Steinberg, J. Food Sci., 52 (1987) 806-809. (941) S. J. Richardson, I. C. Baianu, and M. P. Steinberg, Staerke, 39 (1987) 302-308. (942) S. J. Richardson, I. C. Baianu, and M. P. Steinberg, Staerke, 39 (1987) 79-83. (943) P. Chinachoti and T. R. Stengle, J. Food Sci., 55 (1990) 1732-1734. (944) P. Chinachoti and M. P. Steinberg, J. Food Sci., 54 (1989) 691-694. (945) P. Chinachoti, V. A. White, L. Lo, and T. S. Stengle, Cereal Chem., 68 (1991) 238-244. (946) J. M. Johnson, E. A. Davis, and J. Gordon, Cereal Chem., 67 (1990) 286-291. (947) S. Gardel, Acta Chem. Scand., 7 (1953) 201-206. (948) S. A. Brown and D. French, Carbohydr. Res., 59 (1977) 203-212. (949) L. M. Hansen, J. V. Paukstelis, and C. S. Setser, Cereal Chem., 64 (1987) 449-451. (950) H. Lim, C. S. Setser, J. V. Paukstelis, and D. Sobczynska, Cereal Chem., 69 (1992) 382-386. (951) H. Lim, C. S. Setser, and J. V. Paukstelis, Cereal Chem., 69 (1992) 387-390. (952) R. D. Spies and R. C. Hoseney, Cereal Chem., 59 (1982) 128-131. (953) 1. D. Evans and D. R. Haisman, Staerke, 34 (1982) 224-231. (954) M. L. Bean, W. T. Yamazaki, and D. H. Donelson, Cereal Chem., 55 (1978) 945-951. (955) P. Tomasik, Y. J. Wang, and J. Jane, Staerke, 47 (1995) 91-95. (956) A. Frieden, Chem. Ind., 59 (1946) 641-644. (957) H. Schmalfuss, H. Schoppe, and R. Recke, Kolloid-Z., 116 (1950) 161-170. (958) W. Ghidalia, R. Vendrely, and Y . Coirault, Bull. SOC.Chim. BioL, 52 (1970) 110-112. (959) J. Stofko, South African Pat. 75,00,551 (1975); Chem. Abstr., 85 (1976) 162262~. (960) V. Vesely, Listy Cukrovar., 79 (1903) 93-97. (961) V. G. Gambazirnalayan, Prom. Arm., (8) (1970) 59-61. (962) A. Delauney, M. Henon, S. Bazin, and M. Pelletier, C. R. Acad. Sci., 241 (1955) 10941095. (963) G. L. Ciottoli Sollazzo, Tec. Molitoria, 17 (1966) 57-60. (964) W. S. Davey and K. C. Sekar, Proc. 2nd Rubber Technol. Conf, London, 1948, (1948) 185-191; Chern. Abstr., 44 (1950) 3277. (965) L. B. Crossland and H. H. Favor, Cereal Chem., 25 (1948) 213-220. (966) W. G. Bechtel, Baker’s Digest 33 (December) (1959) 74. (967) R. M. Sandstedt and R. C. Abbott, Cereal Sci. Today, 9 (1964) 13-18, 26. (968) C. A. Watson and J. A. Johnson, J. Food Sci., 30 (1965) 450-456. (969) H. Bloemendal, J. Chromatogr., 2 (1959) 121-135.

(924) (925) (926) (927) (928)

422

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

H. Bloemendal, J. Chromatogr., 3 (1960) 1-10, H. Bloemendal, J. Chromatogr., 3 (1960) 509-519. C. Altauer, Chem. Listy, 56 (1962) 334-354. P. Reichard, Nature, 162 (1948) 662. J. Newell, Hule Mex. Plasr., 36 (422) (1981) 26. G. Hampel, Brot Gebaeck, 22 (1968) 185-192. N. L. Stewart and K. Kingswood, J . Sci. Food Agr., 28 (1977) 11-19. D. H. Simmonds, K. K. Barlow, and C. W. Wright, Cereal Chem., 50 (1973) 553-563. G. D. A. Lowy, J. G. Sargent, and J. D. Schofield,J. Sci. Food Agric., 32 (1981) 371-377. N. P. Badenhuizen, The Biogenesis of Starch Granules in Higher Plants, AppletonCentury-Crofts, New York, 1969. (980) H. E. Wright, Jr., W. W. Burton, and R. C. Berry, Jr., Phyrochem., 1 (1962) 125-129. (981) L. B a h t and J. Homirovic-Culjat, Bull. Sci. Cons. Acad. Sci. Arts RSF Yugosl., Sect. A, 21 (1976) 218-221. (982) V . V . Sirotkin, V. F. Golenkov, L. G. Prezzhaeva, and V. M. Gilzin, Tr VNIl Zerna i Prod. ego Pererab., 83 (1976) 112-118; Ref: Zh., Khim., (1977) Abstr. No. 2R134. (983) S. H. Imam, J. Cereal. Sci., 9 (1989) 213-216. (984) V. B. Tolstoguzov, V. Ya. Grinberg, and L. J. Fedotova. Izv. Akad. Nauk SSSR. Ser. Khim., (12) (1969) 2839-2840. (985) V . B. Tolstoguzov and V. Ya. Grinberg, Izv. Akad. Nauk SSSR. Ser. Khim., (6) (1970) 1423-1424. (986) R. Scott, J. Chem. Phys., 17 (1949) 279-284. (987) G. V. Struminskii and G. L. Slonimskii, Zhurn. Fiz. Khim., 30 (1956) 1941-1947. (988) S. M. Lipatov and G. V. Lipatov, Kolloid. Zh., 21 (1960) 517-521. (989) V. Ya. Grinberg, V. B. Tolstoguzov, and G. L. Slonimskii, Kolloid. Zh., 33 (1971) 666-669. (990) V. Ya. Grinberg and V. B. Tolstoguzov, Carbohydr. Res., 25 (1972) 313-321. (991) L. K. Dahle, Cereal Chem., 48 (1971) 706-714. (992) K. Yagi and K. Okamoto, Nippon Nogei Kagaku Kaishi, 50 (1976) 327-329; Chem. Abstr., 8 (1977) 3747k. (993) A. Dobry, Bull. SOC. Chim. Belg., 57 (1948) 280-285. (994) M. W. Beijerinck, Kolloid-Z., 7 (1910) 16-20. (995) W. Ostwald and R. H. Hertel, Kolloid-Z., 47 (1929) 258-261; 357-370. (996) L. Berczeller, Biochem. Z., 66 (1914) 207-217. (997) S. J. Przylecki and R. Majmin, Biochem. Z., 271 (1934) 168-173. (998) H. Terayama, J. Chem. SOC.Jpn., 78 (1957) 1261-1268. (999) I. Takeuchi and K. Shimada, J. Agr. Chem. SOC.Jpn., 39 (1965) 83-88 89-94. (1OOO) I. Takeuchi and K. Shimada, J. Agr. Chem. SOC.Jpn., 41 (1967) 260-270. (1001) I. Takeuchi, K. Shimada, and S. Nakamura, J. Agr. Chem. SOC.Jpn., 42 (1968) 33-39; 40-48; 294-299. (1002) I. Takeuchi, Cereal Sci., 46 (1969) 570-579. (1003) E. E. Woodside, G . F. Trott, R. J. Doyle, and C. W. Fishel. Arch. Biochem. Biophys., 11 (1966) 125-133. (1004) J. A. Maga and 0. 0. Fapojuwo, J. Food Technol., 21 (1986) 61-66. (1005) B. A. Nikolaev and S. S. Shkadina, Izv. Vyssh. Uchebn. Zaved., Pishch. Tekhnol. (3) (1964) 56-59. (1006) B. A. Nikolaev and I. A. Samarina, Khlebopekarn. Kondit. Prom., 2(3) (1958) 3-8. (1007) P. Kassenbeck, Cereal Foods World, 23 (1987) 494. (1008) B. A. Nikolaev, Dokl. Akad. Nauk SSSR, 90 (1953) 595-598. (1009) K. Hess, Muehle, 95 (1958) 543-545. (970) (971) (972) (973) (974) (975) (976) (977) (978) (979)

COMPLEXES O F STARCH WITH ORGANIC GUESTS

423

(1010) M. Hishino, K. Tanaka, and K. Mitsugi, German Pat. 2,262,334 (1973); Chem. Absrr., 79 (1973) 76967~. (1011) S . Nakamura, K. Takeo, and I. Sasaki, Z. Physiol. Chem., 328 (1962) 139-144. (1012) R. M. Sansstedt and S. Ueda, Denpun Kogyo Gukkuishi 17 (1969) 215-228; Chem. Absrr., 72 (1970) 128863n. (1013) A. N. Emery, S. A. Barker, and J. M. Novais, Ger. Pat. 2,206,360 (1972); Chem. Absrr., 78 (1973) 13345b. (1014) S . Ueda, Denpun Kuguku, 25 (1978) 124-131; Chem. Absrr., 91 (1979) 106858e. (1015) J. R. Roozen and W. Pilnik, Lebensm. Wiss. Technol., 4 (1971) 196-200. (1016) V. M. Lelong, P. Colonna, and S. G. Ring, Biorechnol. Bioenerg., 38 (1991) 127-134. (1017) C. Seigner, C. E. Provdanov, and G. Marchis-Mourens, Biochem. Biophys. Acru. 913 (1987) 200-209. (1018) J. A. Thoma, C. V. Rao. C. Brothers, and J. Spradlin,J. Biol. Chem., 246 (1971) 56215635. (1019) Y. Kozaki and H. Inoue, Hukko Koguku Kuishi, 62 (1984) 111-117; Chem. Absrr., 101 (1984) 225779q. (1020) A. N. Petrova and R. L. Filippova, Dokl. Akud. Nuuk SSSR, 169 (1966) 703-704. (1021) A. N. Petrova and R. D. Filippova, Dokl. Akud. Nuuk SSSR, 162 (1965) 455-457. (1022) A. N. Petrova, R. D. Filippova, and A. A. Kobzeva, Biokhimiyu, 31 (1966) 1079-1083. (1023) K. Doi and Z. Nikuni, Sruerke, 14 (1962) 461-465. (1024) Hsin Yan Chung and M. M. MacMasters, Stuerke, 18 (1966) 377-382. (1025) V. Sochor, Czechoslovak Pat. 142,259 (1971); Chem. Absrr., (1972) 60332j. (1026) A. Hermansson and 1. Marie, Dutch Pat. 77,11,010 (1978); Chem. Abstr., 89 (1978) 89127~. (1027) A. Hermansson and 1. Marie, U.S. Pat. 4,159,982 (1979); Chem. Absrr., 91 (1979) 106874g. (1028) A. Hermansson and 1. Marie, British Pat. 1,602,505 (1981); Chem. Abstr., 96 (1982) 179784r. (1029) J. Lelievre and J. Husbands, Stuerke, 41 (1989) 236-238. (1030) R. L. Hawley, French Pat. 1,576,222 (1969); Chem. Absrr., 72 (1970) 77655m. (1031) Z. D. Zhuravleva, A. R. Sapronov, A. I. Zhushman, N. L. Rybalko, N. N. Tregubov, and V. V. Krylova, USSR Pat. 825,635 (1981); Chem. Abstr., 95 (1981) 6412031. (1032) J. H. Cagle, U.S. Pat. 2,286,259 (1942); Chem. Absrr., 36 (1942) 7318. (1033) F. 0. Giesecke, U S . Pat. 1,974,454 (1934); Chem. Abstr., 28 (1934) 7445. (1034) J. Andres, P. Hasenkamp, and H. Merkel, European Pat. Appl. E P 80,141 (1983); Chem. Absrr., 99 (1983) 89835r. (1035) F. 0. Giesecke, U.S. Pat. 1,939,973 (1934); Chem. Absrr., 28 (1934) 1564. (1036) M. Vuk and S. Goemoery, Hungarian Pat. 101,845(1929); Chem. Abstr., 25 (1931) 2493. (1037) C. G. Rehfeld, Ernuehrungsforschung, 8 (1963) 510-516. (1038) T. Ojima, 1. Yamamura, and T. Kumagaya, Denpun Kuguku, 33 (1986) 183-190; Chem. Absrr., 106 (1987) 3942b. (1039) V. B. Tolstoguzov, in J. R. Mitchell and D. A. Ledward (Eds.), Functional Properties of Food Macromolecules, Elsevier Appl. Sci. Publ. London, 1986, Ch. 9. (1040) V. B. Tolstoguzov, Nuhrung, 18 (1974) 523-531. (1041) A. N. Nesmeyanov, V. M. Belikov, C. V. Rogozhin, G. L. Slonimskii, R. V. Golovnya, and V. B. Tolstoguzov, Vestn. Akud. Nuuk SSR, (1) (1969) 27-44. (1042) G. Boison, M. V. Taranto, and M. Cheryan, J. Food. Technol., 18 (1983) 719-730. (1043) D. Berrington, A. Imeson, D. A. Ledward, J. F. Mitchell, and J. Smith, Curbohydr. Polym., 4 (1984) 443-460.

424

PlOTR TOMASIK AND CHRISTOPHER H. SCHILLING

(1044) J. 1. Tschimirov, T. V. Kislova, E. E. Braudo, F. R. Schierbaum, E. S. Strashchenko, V. B. Tolstoguzov, and S. Augustat, Nahrung, 23 (1979) 501-508. (1045) C. L. Logue, Canadian Pat., 403,788 (1942); Chem. Abstr., 36 (1942) 14280g. (1046) Corn Products Refining Co., French Pat. 852,825 (1940); Chem. Abstr., 36 (1942) 2438. (1047) C. H. Champion and F. H. Denham, U.S. Pat. 2,258,741 (1942); Chem. Absrr., 26 (1942) 592. (1048) B. I. Komarova, Yu.F. Barbolin, V. E. Marker, E. A. Shlyrkova, A. V. Antonova, and 0. V. Yurin, USSR Pat. 472,998 (1975); Chem. Absfr., 83 (1975) 117504~. (1049) Z. Myslinska, M. Jedrzejak, W. Kroczak, K. Palenik, E. Bregula, and L. Gorski, Polish Pat. 72,068 (1974); Chem. Absfr., 83 (1975) 45117. (1050) M. J. Mentzer, U.S. Pat. 3,351,480 (1967); Chem. Abstr.. 68 (1967) 142808. (1051) J. J. Putscher, French Pat. 37,165 (1929); Chem. Abstr., 25 (1931) 2493. (1052) J. D. Christianson, J. E. Hodge, D. Osborne, and R. W. Detroy, Cereal Chem.. 58 (1981) 513-517. (1053) C. Fellers, Pure Products, 13 (1917) 177-185. (1054) A. A. Morozov and S. T. Ogrodnik, Kolloid. Zh., 12 (1950) 452-459. (1055) P. M. Arkhangelskii, 1. A. Kalashnikov. and V. S. Gryuner, Sakh. Prom., 41 (9) (1967) 50-53. (1056) W. E. Dudacek, D. A. Kochan, and H. E. Zobel, US Pat. 4,491,483 (1985); Chem. Abstr., 102 (1985) 111887~. (1057) D. Heath and P. Lees, British Pat. 2,021,948 (1979); Chem. Abstr., 92 (1980) 220694~. (1058) Toppan Printing Co., Ltd., Jpn Tokkyo Koho, 81,42,636 (1981); Chern. Abstr., 96 (1982) 87378h. (1059) A. S. Wahl, U S . Pat., 1,795,980 (1931); Chem. Abstr., 25 (1931) 2493. (1060) A. M. Golal and J. A. Johnson, Bakers Dig., 50(12) (1976) 20-22. (1061) Corn Products Co., French Pat., 1,376,126 (1924); Chem. Absrr., 62 (1965) 12008. (1062) W. H. Houf and A. C. Nixon, US. Pat. 3,321,422 (1967); Cliem. Abstr., 67 (1967) 65708q. (1063) K. Sakakibara and F. Iwase,Jpn Kokai Tokkyo Koho, 63,251,486 (1988); Chem. Abstr., 110 (1989) 2565411. (1064) G. H. Klein, H. L. Arons, J. F. Stejskal, D. G. Stevens, H. F. Zobel, and L. Wondolowski, German Pat. 2,633,048 (1977); Chem. Abstr., 86 (1977) 173394k. (1065) J. A. Thoma, H. B. Wright, and D. French,Arch. Biochem. Biophys., 85 (1959) 452-460. (1066) Y. Y. Talib, M. S. Karve, S. V. Bhide, and N. R. Kale, J. Chromatogr. 403 (1987) 373-378. (1067) M. Ulmann and B. Wendt, Kolloid-Z., 142 (1956) 157-168. (1068) M. Samec, Ber., 73A (1940) 85-92. (1069) E. Pascu and J. W. Mullen, 2nd, J. Am. Chem. Soc.. 63 (1941) 1168-1169. (1070) R. W. Ashword, T. H. Evans, and H. Hilbert, Can. J. Res., 24B (1946) 246-253. (1071) K. H. Meyer and G. C. Gibbons, Helv. Chim. Acra. 33 (1950) 210-213. (1072) N. B. Patil, S. P. Taskar. and N. R. Kale, Carbohydr. Res., 39 (1974) 171-174. (1073) C. Tauret, C. R. Acad. Sci., 158 (1914) 1353-1354. (1074) K. W. Kerr, Paper TradeJ., 115 (1942) 30-34. (1075) R. W. Kerr and N. E. Schink, Paper Trade J., 120 (1945) 86-88, 90. (1076) R. W. Kerr and G. M. Severson, J. Am. Chem. Soc., 65 (1943) 193-198. (1077) M. C. Brooks and R. M. Badger, J. Am. Chem. Soc., 72 (1950) 4384-4388. (1078) B. Dernikovic and B. Lovrecek, Hem. Znd., 39 (2) (1985) 35-40. (1079) P. Vullette and J. Rouger, Prod. Quim. Aux. Znd. Papefera [Curso], (1982) 45-87; Chem. Abstr., 101 (1984) 173260s. (1080) H. S. Lee, P u l p Chongi Gisul, 19(1) (1987) 33-45; Chem. Absfr., 107 (1987) 79845~.

COMPLEXES O F STARCH WITH ORGANIC GUESTS

425

(1081) J. Roberts, Proc. Tech. Sect., Paper Makers Assoc. Gt. Brit. & Ireland, 19 Pt. 2 (1939) 439-446. (1082) F. Holt, Paper Ind., Paper World, 21 (1939) 332-334. (1083) E. E. Stephenson, Paper Ind., 33 (1951) 413-416. (1084) W. Lueckenhaus, Wochenbl. Pupierfubr., 115 (1987) 100-102. (1085) A. Lutz, Pupier Ztg., 33 (1979) 314. (1086) E. Tromp, Pupierfubr., 23 (1925) 109-111. (1087) A. Lutz, Wochenbl. Pupierfubr., 39 (1908) 404-561. (1088) H. M. Grasselt, Paper Ind., 7 (1925) 900-901. (1089) T. E. Blasweiter, Wochenbl. Pupierfubr., 56, Sondernummer (1925) 89-93. (1090) J. Traquair, Puper, 26 (1920) 93-96. (1091) M. Samec, Oesterr. Chemiker Ztg., 63 (1) (1961) 12-17. (1092) S. Hernadi and P. Voelgyi, Pupiripar, 23 (1979) 51-55. (1093) S. Hernadi and P. Voelgyi, Wochenbl. Pupierfubr., 106 (1978) 353-358. (1094) J. A. Benckiser G. m. b. H. Chemische Fabrik, German Pat. 1,216,236 (1966); Chem. Absrr., 66 (1967) 11812e. (1095) R. Taubert and F. Freitag, German Pat. 2,455,552 (1976); Chem. Abstr., 85 (1976) 349304.. (1096) D. W. Akerson, U.S. Pat. 4,024,014 (1977); Chem. Absrr., 87 (1977) 7810u. (1097) A. Bondoc, E. J. Flood, and F. W. Sieling, U.S. Pat., 4,472,243 (1984); Chem. Absrr., 101 (1984) 2155783’. (1098) A. Brucato, U.S. Pat. 4,609,432 (1986); Chem. Abstr., 106 (1987) 68986~. (1099) V. E. Guryanov and L. 1. Semkina, USSR Pat. 1,268,649 (1986); Chem. Abstr., 107 (1987) 9180~. (1100) J. Marton and T. Marton, Tuppi, 59 (12) (1976) 121-124. (1101) M. Nedelceva, Pup. Celul., 33 (1978) 7-8. (1102) W. Jarovenko, U S . Pat., 3,721,575 (1973); Chem. Abstr., 78 (1973) 149155~. (1103) K. Shimono, H. Kuwahara, N. Matsuoka, and K. Kohara, Shizuoku-Ken Seishi Kogyo Shikensho Shikeu Kenkyu Hokokusho, (23) (1971) 12-26 Chem. Abstr., 79 (1973) 20538r. (1104) M. Pancu and G. Iliescu, Celul. H i de, 22 (1973) 502-504. (1105) E. I. Kovalevskaya and 0. D. Kurilenko, Ukr. Khim. Zh., 41 (1975) 205-206. (1106) E. Nishide, Nippon Shokuhin Kogyo Gukkaishi, 14 (1967) 204-207; Chem. Abstr., 68 (1 968) 2019r. (1107) Z. lnsinski and S. Magdzik, Polish Pat., 61,006 (1970) Chem. Abstr., 71 (1971) 54585r. (1108) J. Zborowski and L. Obroniecka, Polish Pat., 130,190 (1985); Chem. Abstr., 107 (1987) 116605h. (1 109) R. E. Hoult and R. H. Cairns, Canadian Pat., 78 (1973) 86264j. (1110) M. Matsumoto, S. Hamano, and T. Hirabayashi, Japanese Pat., 73 10,377(1973); Chem. Absrr., 80 (1974) 61367~. (1 111) Toa Gosei Chemixcal Industry Co., Ltd., Jpn. Kokui Tokkyo Koho, 82 42,755 (1982); Chern. Absrr., 97 (1982) 24717t. (1112) T. Kitamura, H. Miyazaki, H. Maruyama, and K. Abe, Jpn Kokui Tokkyo Koho, 02 84,450 (1990); Chem. Abstr., 113 (1990) 42711. (1 113) K. Takano, K. Moriya, T. Sato, J. Yamauchi, and T. Okaya, Jpn Kokui Tokkyo Koho, 62,288,643 (1987); Chem. Abstr., 108 (1988) 169547t. (1114) K. Takano, K. Moriya, T. Sato, J. Yamauchi, and T. Okaya, Jpn Kokui Tokkyo Koho, 62,288,644 (1987); Chern. Abstr., 108 (1988) 169548. (1115) Oiji Cornstarch Co., Ltd. Rengo K. K., Jpn. Kokui Tokkyo Koho, 60 42,475 (1985); Chem. Abstr., 103 (1985) 72848.

426

PIOTR TOMASIK AND CHRISTOPHER H. SCHILLING

(1116) S. Koizumi, Jpn. Kokai 77,155,638 (1977); Chem. Abstr., 88 (1978) 172244r. (1117) R. W. Monte and J. D. Sordillo, Adhes. Age. 18(4) (1975) 38-39. (1118) Honshu Paper Co., Ltd. Jpn. Kokui Tokkyo Koho 81,159,154 (1981); Chem. Abstr., 96 (1982) 1448082. (1119) J. A. Faber and P. L. Krankkala, European Pat. Appl., 383,214 (1990); Chem. Absrr., 113 (1990) 214162f. (1120) R. K. Britton, U.S. Pat., 3,133,890 (1964); Chem. Abstr., 61 (1964) 3289. (1121) National Starch and Chemical Corp., British Pat., 1,137,603 (1968); Chem. Abstr., 70 (1969) 48868m. (1122) E. Drzewinska, Przegl. Papier., 28 (1972) 366-369. (1123) Lonza Elektrizitaetswerke und Chemische Fabriken Akt.-Ges., British Pat.. 839,204 (1960); Chem. Abstr., 54 (1960) 21872. (1124) C. H. Craig and M. A. Silano, US.Pat. 4,424,291 (1984); Chem. Abstr., 100 (1984) 105454. (1125) R. Fukomori, Japanese Pat., 72 44,015 (1972); Chem. Abstr., 80 (1969) 72278~. (1126) Mitsubushi Electric Corp., Jpn. Kokui Tokkyo Koho, 57,202,363 (1982); Chem. Absrr., 9 (1983) 200151k. (1127) Oiji Cornstarch Co., Ltd., Jpn. Kokai Tokkyo Koho, 59,152,969; Chem. Absrr., 102 (1985) 133922~. (1128) K. Miyake, T. Yamada, and K. Kikuchi, Jpn. Kokai Tokkyo Koho, 79 69,142 (1979); Chem. Absrr., 91 (1980) 159336q. (1129) M. Takatsuji, S. Miyake, T. Nakai, M. Tokuda, and K. Kikuchi, Jpn. Tokkyo Koho, 78 44,176 (1975); Chem. Abstr., 90 (1979) 105201~. (1130) Hohnen Oil Co., Ltd., Jpn. Kokai Tokkyo Koho, 57,139,158 (1982); Chem. Absrr., 98 (1983) 55897. (1131) J. F. Lowey and T. V. Frommherz, US Put., 3,988,495 (1976); Chem. Abstr., 86 (1977) 18676k. (1132) A. G. Penczuk and J. Sirota, US.Pat.,4,336,166 (1982); Chem. Abstr., 97 (1982) 94364a. (1133) M. Nakamura, N. Mitsui, T. Kato, and S. Konishi, Jpn. Kokai, 74,122,551 (1974); Chem. Abstr., 82 (1975) 141278b. (1134) P. Hoffman and H. W. Craig, U.S. Pat., 3,696,065 (1972); Chem. Abstr., 78 (1973) 30997h. (1135) T. Iwasaki, Japanese Pat. 73,07,257 (1973); Chem. Absrr., 80 (1974) 4369b. (1136) Y.Iida and Y. YokoyamaJpn. Kokui76,116,839(1976); Chem. Abstr., 86 (1977) 56453t. (1137) W. J. Opie, British Pat., 906,562 (1958); Chem. Abstr., 58 (1963) 3575. (1138) K. Takahashi, Jpn. Kokai, 75,129,631 (1975); Chem. Abstr., 84 (1976) 76054a. (1139) Z. Maj, Przegl. Papier., 30 (1974) 25-29.

AUTHOR INDEX A

Ando, T., 202, 210, 239,258(17), 260(81) Andres, J., 410,423(1034) Andrews, A. C., 309,337(432) Andrews, L. W., 265, 328(32) Anfinsen, C. B., 202,258(12) Anglade-Thevenet, S.,280, 331(161) Angulescu, E., 264, 265, 328(29, 33) Animati, F., 104, 140(274) Anisuzzaman, A. K. M., 77, 138(200) Antonova, A. V., 411, 423(1048) Apalkova, N. N., 297, 335(317) Aplin, R. T., 51, 75, 77, 136(113) Apostolopulos, D., 308, 337(417), 360 Aqueel, A,, 104, 140(275) Arai, K., 326, 327,342(630, 644) Araki, K., 105, 140(283) Arasappan, A., 78,138(202) Arcamone, F., 104, 140(274) Archibald, A. R., 278, 284, 331(146) Arkhangelskii, P. M., 402,411,412, 420(920), 424(1055) Arons, H. L., 412,424(1064) Arthur, P., 296, 333(235) Asboth, J., 324, 341(579) Asensio, J. L., 76, 138(196) Ashword, R. W., 412,424(1070) Askonas, B. A., 235,260(77) Asp, N.-G., 400,420(894, 895) Aspinall, G. O., 73, 78,80, 81, 98, 137(174), 138(203, 139(225) Assef, A. G., 303,336(380) Asteriadis, G. T., 85, 140(256) Attwood, S. V., 186, 187, 198(137) Aub6, J., 44,48, 135(97) Auge, C., 73, 129,137(172), 142(347) Augeri, D., 79, 126, 127, 139(221) Augustat, S., 281,296,297,303,332(187), 334(283,297), 336(382), 386, 411, 423( 1044) Auzanneau, F.-I., 85, 99, 115, 121, 140(252, 253), 141(311) Avery, 0. T., 217, 259(50, 51) Axen, R., 202,204,258(13) Ayadi, E., 162, 163,166, 167, 197(68, 74, 78) Ayala, A. M., 44,45, 46,48, 135(100)

Abadie, P., 303, 311, 336(368, 370) Abad-Rodriguez, J., 76, 138(196) Abbas, S. A., 75, 138(189) Abbott, R. C., 405,421(967) Abdali, A., 105, 140(279) Abdel-Kerim, A., 298, 335(322) Abe, K., 413,425(1112) Abraham, W. H., 309, 337(423) Achiwa, K., 186, 187, 198(136) Acker, L., 368, 385, 386, 387, 416(746), 418(828-830, 835, 836, 845) Adkins, G. K., 282, 332(195) Adlington, R. M., 186, 198(115) Afenya, P. M., 313, 338(460) Aitken, T., 325,342(606) Akamatsu, S.. 186, 187, 198(136) Akerson, D. W., 412,425(1096) Akimoto, S., 363, 415(710) Alais, J., 26, 32, 34, 42, 75, 76, 80, 134(57), 138(191) Albano, E., 180, 198(97b) Alekseeva, I. I., 281, 326, 332(193), 342(618) Alferov, V. V., 297, 334(310) Alfoldi, J., 177, 197(90) Aliev, N. Ya., 297, 334(310) Allen, P.Z., 204,217, 229, 258(26), 259(52, 53) Almendral Parra, M. J., 296,333(243) Alonso Mateos, A., 296, 333(243) Altauer, C., 405,421(972) Altschul, A. M., 350,414(672) Altshuter, Yu. Z., 306, 337(408) Amakai, H., 366,415(723a) Amakai, T., 349, 352. 414(661) Amano, J., 78, 138(206) Amareseka, A. S., 162, 197(66) Ames, A,, 185, 198(108) Ames, B. N., 206, 208, 215, 258(35) Anderson, D. M. W., 270, 329(74) Anderson, J. S., 202, 215, 232, 250, 258( 15, 32) Anderson, L., 32, 36, 54, 55, 67, 68,69, 70, 73.74, 77, 82, 105, 106, 131, 134(66), 136(132), 137(168-170), 138(181,200) Anderson, W. K., 105, 140(280) 427

428

AUTHOR INDEX

Ayche, J. B., 296, 334(274) Azudin, M. N., 386, 396,418(838), 419(877)

B Baas-Becking, L. G. M., 269, 296, 329(71) Babers, F. H., 217, 259(51) Babirad, S. A., 177, 197(93) Baczkowicz, M., 264, 271, 301, 302, 328(3), 336(353, 355), 352, 354,357,358, 359, 367, 373, 374,414(678,683,684) Badenhuizen, N. P., 384,406,417(809,810), 422(979) Badger, R. M.. 412,424(1077) Badolato, F., 296,332(227) Baer, H. H., 51, 73, 136(112), 137(175) Baeziger, J., 202, 258(21) Baianu, 1. C., 403,421(940-942) Bailey, J. M., 268, 274, 275, 284, 329(64), 330(114) Baimbridge, C. L., 148, 196(37) Bajkin, D., 373,416(758) Baker, D. A., 217,259(55) Baker, R., 82, 139(234) Baker, R. E., 321, 340(545) Bakshi, P. K., 19, 24, 25, 27, 28, 29, 30, 124, 133(21), 134(42, 60) Balducci, R.,162, 197(67) Baldwin, J. E., 186, 198(115) Baldwin, R. R., 264, 274, 275, 276, 277, 284, 290, 303, 328(18). 330( 106, 110, 123). 398,411, 419(885) Balejee, S. R., 313, 338(461) B a h t , L., 406, 422(981) Ball, D. B., 185, 198(110) Ball, E. M., 247, 260(91) Ballou, C. E., 255,261(105) Balls, A. K.. 349, 414(664) Baltas, M., 105,106, 107,140(272) Bamburg, J. B., 244, 260(84) Bamford, M. J., 77, 138(198) Banasik, O., 319, 339(514) Bancher, E., 296,333(238), 383, 417(805) Banks, C. H., 148, 149, 196(42) Banks, W., 264, 281, 304, 328(14), 332(185), 336(385), 346,359 Banky-Eloed, E., 371,372,416(753) Banoub, J., 167, 197(77) Baranowska, H. M., 361,415(697) Barbalat-Rey, F., 177, 197(91)

Barbolin, Yu.F., 41 1, 423( 1048) Barger, G., 264,265, 268, 328(8, 24, 40) Barham, H. N., 349,414(663) Barker, R., 133, 142(354) Barker, S. A., 409, 410, 422(1013) Barlow, J. J., 80, 139(226) Barlow, K. K., 405,422(977) Barrett, A. G. M., 186, 187, 198(129, 130, 137) Barrow, R. A., 19, 113, 133(14) Barton, D. H. R., 186, 187, 198(129) Basak, A., 186, 198(115) Bassler, W. D., 302, 336(365) Basten, J. E. M., 73, 137(163) Bates, F. L., 268,269,270,274,303, 329(65) Bates, P. A., 24, 27, 29, 30, 134(40) Batisse, E. M., 327, 342(634) Bauer, A., 350, 351, 352, 354, 365, 366, 367, 372, 373,414(674) Bauer, F., 112, 141(295) Baxter, E. W., 114, 123, 141(308) Bayer, E., 327, 343(646, 647) Bayley, H., 167, 197(75) Bazin, S., 405, 421(962) Bean, M. L., 402,403,404,420(921), 421(934, 954) Bear, R. S., 274,284, 303, 330(106), 363, 415(707) Bear, S., 265, 308, 328(46), 346 Beau, J.-M., 73, 104, 106, 107, 108, 110, 137(178), 140(267,284), 141(287,290), 154, 156, 157, 186, 187, 196(60), 197(62). 198(124) Beccaria, A. M., 326, 342(623) Bechtel, W. G., 405, 421(966) Beck, P., 52, 61, 101, 103, 136(115) Becker, G., 386, 387, 418(835, 845) Bednarski, M., 201, 258(2) Beijerinck. M. W., 408, 422(994) Beldii, V. V., 301, 336(360) Belikov, V. M., 411, 423(1041) Belogurova, A. F., 316, 339(485) Belzynska, M., 327, 342(637) Benckiser, J. A., 412, 425(1094) Benedict, C. R., 144, 195(2) Beppu, K., 126, 142(328) Berard, P. A., 313,338(453) Berczeller, L., 400,408,420(901), 422(996) Berczeller, R., 264, 265, 328(25, 34) Berettoni, M., 104, 140(274)

AUTHOR INDEX Berezovskaya, N. N., 374,416(772) Berg, R. A., 287,293, 332(210) Berggren, M., 83, 139(245) Bergmann, M.. 264, 328(26) Bergmann, S., 265, 328(39) Bernabe, M., 20, 21, 22, 26, 33, 34, 35, 36, 51, 55. 129, 134(36), 136(114), 142(348) Bernet, B., 49, 50, 51, 53, 61, 68, 69, 72, 77, 96, 97, 101. 103, 135(107) Bernfeld, P., 266, 268, 274, 329(58), 366, 415(722,723) Berrington. D.. 411,423(1043) Berry, R. C., Jr.. 406, 422(980) Berschneider, F., 403,421(931) Bersohn, R., 287, 288, 293, 332(209,211) Bertozzi, C. R., 52, 61, 75, 77, 101, 103, 136(115), 138(185), 201, 258(2) Berube, G.. 186, 187, 198(128) Besford, L. S., 400, 402, 420(910) Bessonov, S. M., 374, 416(772) Beszterda. A,, 296, 333(240) Betaneli, V. 1.. 72. 96, 137(162) Bettelheirn, F. A., 298, 335(323) Beuther, A., 145, 195(11) Beyler, M., 353. 355, 359, 363, 365, 366, 367, 373, 414(680) Beynon, P. J., 20, 21, 24, 25, 26, 33, 34, 134(35) Bhatia, R. K. S., 301, 336(354) Bhattacharyya. S., 274, 296, 330(105) Bhide, S. V., 412, 424(1066) Biedermann, W., 319, 340(527, 528) Bilik, V., 131, 132, 133, 142(352, 353) Billington, D. C., 82, 139(234) Bilodeau, M. T., 74, 101, 106, 128, 138(182), 142(346) Birnbenet, J. J., 304,336(394) Birch, G. G., 323, 341(573) Bittman, R., 46, 111, 112, 135(103), 141(294) Bizot, H., 303, 336(376, 377) Bizzozero. N., 177, 197(91) Bjoerck, J.. 400, 420(594, 89.5) Blacker, A. J., 106, 141(293) Blankestijn, J., 395, 396, 419(865) Blanksrna, J. J., 365, 415(719) Blasweiter, T. E., 412, 425(1089) Blatter, G., 70, 137(155) Bloemendal, H., 405,421(969-971)

429

Bluhm, T. L., 276, 277,330(134) Blumberg, K., 148,196(34) Blunden, S. J., 17, 20, 21, 24, 25, 26, 33, 34, 133(5), 134(32, 35) Boa, P., 297,334(304) Bobkova, A. S., 297,335(319) Boesh, T. F., 301, 306, 336(359) Boison, G., 411,423(1042) Bolkhovitina, Yu. R., 320, 340(532) Bondoc, A,, 412,425(1097) Bonner, W. A., 145, 195(14) Boons, G.-J., 19, 44,46, 49, 51, 85, 111, 115, 116, 121, 122, 133(12, 13), 140(254), 141(310) Booth, R. J., 106, 141(293) Borbis, A., 79, 138(213) Bordier, H., 293,332(221,223) Borisov, L. B., 297, 334(307, 308) Bornmann, W. G., 186, 187, 198(131) Borochoft, E. H., 388,389,418(849) Borowiecka, J., 152, 196(51) Boruch, M., 311,312,323, 324,338(443), 341(571) Boshagen, F.-R., 8.5, 140(250) Bouchard, H., 85, 140(251) Boullanger, P., 167, 197(77) Bourne, E. J., 296,316,334(281), 339(482), 397, 399,419(884) Bousquet, E., 52, 136(121) Boutriac, A., 268, 280, 320, 329(60), 331(161), 340(538) Bowler, P., 387,418(841, 842) Boyce, C. R., 239, 260(78) Boyer, S. H., 79, 106, 118, 138(210, 211) Boyko, J., 162, 163, 165, 197(69) Brakke, M., 206, 258(31) Brandenburg, A,, 24,134(45) Brandt, R. G., 364, 415(713) Brant, D. A., 274, 279, 281, 330(113), 346, 414(651, 6.52) Braudo, E. E., 411, 423(1044) Brauner-Glaesner, G., 368, 416(746) Bravos, G. T., 324, 341(575) Breaker, R. R., 86, 140(256) Brebant, R., 310, 338(436) Bredenkamp, M. W., 41, 95, 106, 117, 118, 123, 131, 132, 135(88), 141(289), 142(350) Bregula, E., 411,424(1049) Brennan, P. J., 73, 137(174)

430

AUTHOR INDEX

Brentano, W., 366, 415(722) Briant, A. M., 402, 403, 420(922) Brimacombe, J. S., 105, 107, 140(270) Britton, R. K., 413, 425(1120) Brockhausen. I., 52, 64,65, 136(122, 123) Brokaw, G. Y.,388,396,418(852) Brooks, M. C., 412,424(1077) Brothers, C., 409,423(1018) Broughton, H. B., 186, 187, 198(130, 137) Brounts, D. M., 82, 83, 139(237) Brown, S. A., 403,404,421(948) Brownic, C. A., 305, 337(397) Browning, B. L., 270,296,329(76) Broxterman, H. J. G., 173, 174, 177, 197(87) Brucato, A., 412, 425(1098) Bruins, E. M., 320, 340(537) Brukhyanova, N. A., 374,375,416(771) Bruna, R., 293, 332(224) Bruni, G., 319,340(526) Brunner, D., 280, 331(178) Brzezinski, S., 311, 312,338(443) Buechner. E. H., 320, 340(537) Buet, V., 33, 86, 134(71) Buleon, A,, 266, 267, 303, 329(51, 52), 336(376,377) Bulian, H. P., 73, 137(167) Bundle. D. R., 174, 197(88), 217, 253, 259(55), 260(99, 101) Bungenberg de Jong, H. G., 299,320, 335(338), 340(535) Burchard, F., 321,340(543) Burgstaller, A., 265, 328(35) Burton, W. W., 406,422(980) Bus, W. C., 323, 335(326), 341(568) Busek, J., 316, 339(487) Bushuk, W., 304, 305, 311, 336(390), 337(401), 357,414(686) Buzagh, A., 317, 339(495) Bychkovskii, N. I., 303, 336(378) Byun, H A . , 46, 135(103)

C

Cagle, J. H., 410, 423(1032) Cairns, R. H., 413,425(1109) Calvo-Flores, F. G., 163, 164, 166, 197(70, 73) Calzolari, C., 319, 340(526)

Cameron, T. S., 19. 24, 25, 27, 28, 29, 30, 124, 133(21), 134(42, 60) Campbell, C. L., 349, 414(663) Campbell, S., 188, 199(148) Canic, V., 319, 340(523. 524). 367, 373, 415(727), 416(733,758) Capdevila, J., 83, 139(243) Carda, M., 112, 115, 122, 141(297, 313) Carillo, P. J., 403,421(938, 939) Carlin, G. T., 396, 398,419(869) Carlin, N. 1. A., 253, 260(99) Carlson, T. G., 392,419(859) Carnell, A,, 85,140(251) Carreaux, F., 112,141(298) Carrillo, P. J., 307, 337(413) Carvo, D., 192, 199(156) Casabo, P., 115, 122, 141(313) Casier, J., 402, 420(914) Castillon, S., 158, 159, 197(63, 64) Castle, G. H., 19, 44, 46, 49, 51, 111, 115, 116, 121, 122, 133(12, 13) Cater, G. H., 296, 333(249) Centola, G., 299, 335(334) Cepure, A., 211, 251, 259(47, 48), 260(96) Cerning-Beroard, J., 402,420(913) Cesario, A., 274, 279,281, 330(113), 332(194) Cesario, M., 29, 30, 134(59) Chahoua, L., 105. 106, 107,140(272) Chambers, R. J., 69, 103, 137(153) Champetier, G., 300,315,335(343), 338(471) Champion, C. H., 411,423(1047) Chan, S., 185, 198(110) Chang, Y.-T., 63, 137(146, 147) Chanzy. H., 266, 329(51) Chapeaux, M., 320,340(538) Chapek, M. V., 301, 312, 335(349). 336(350), 338(448), 361,414(692) Chapelle, S., 20, 133(30) Chaplin, M. F., 365, 415(718) Charbonniere, R., 303,311, 336(368,370, 374), 388,391,418(855) Charles, J., 296, 333(252) Charon, D., 85,99,115, 121, 140(252,253), 141(311) Chattejee, D., 73, 137(174) Cheer, R. L., 402,421(930) Cheesman, E. F., 315, 324, 325, 338(478) Chegoryan, V. M., 360,415(695)

AUTHOR INDEX Chelain, E., 169, 197(79) Chen, A. C., 400,420(907) Chen, C.-S., 52, 56, 63, 82, 136(125, 143) Chen, G. C., 148, 149, 196(38, 39,42) Chen, H.-C., 307, 337(412) Chen, S.-H., 74, 84, 138(180), 139(248) Cherwonogrodzky,J. W., 253, 260(101) Cheryan, M., 411, 423(1042) Chesheva, S. P., 299, 308, 335(335) Chevalier, C. E., 219, 259(57) Chianelli, D., 162, 197(67) Chida, N., 56, 114, 136(144), 141(307) Chinachoti, P., 402,403, 420(925), 421(937. 943-945) Chinball, C., 367, 415(729) Chinoy, J. J., 268, 329(59) Chmielewski. M., 169, 197(79) Cho, S. J., 63, 137(147) Chociej, J., 313, 316, 338(459) Chopra, S. L., 31 1, 338(445) Choudhury, A. K. R., 264,272,293,328(27) Chowdhary, M. S., 73, 137(169) Chrambach, A., 206,232, 258(28) Chretien, E., 296, 333(233) Christianson, J. D., 411,424(1052) Chu, F. C., 402, 420(915) Chu, J. F., 402, 420(915) Chun, K. H., 80, 139(225) Chun, M. W., 113, 141(305) Chung, D. S., 307, 337(412) Chung, H. Y., 410, 423(1024) Chung, S.-K., 52, 63, 136(129), 137(146, 147) Chungcharoen, A,, 402,420(927) Chupa, M. I., 297, 335(318) Ciacco, C. F., 396, 400, 402. 419(878), 420(909) Ciottoli Sollazzo, G. L., 296, 333(262), 334(279). 405. 421(963) Cipollone, A,, 104, 140(274) Clareman, D. A,, 184, 185, 191, 198(103) Claremon, D. A,, 184. 191, 198(102) Clarke, M. A., 402, 420(918) Clase, J. A,, 19, 44, 46, 49, 51, 111, 115, 116, 121, 122, 133(12, 13), 141(310) Clementi, A., 272, 330(97) Clerici, F., 126, 142(335) Cleveland, F.C.. 284, 332(201) Clive, D. L. J., 144, 195(3d) Coburn, R. A,. 105, 140(280)

431

Cohen, A., l80,197(97a) Cohn, M.. 217,259(54) Coirault, Y., 404, 421(958) Coleman, R. S., 104, 108, 140(266) Coligan, J. E., 229, 260(71) Colin, J. J., 264, 328(16) Collings, P., 298, 335(321) Collinson, R., 318, 339(505-507) Colonna, P., 409, 410,423(1016) Conant, R., 83,139(238,239) Conrad, H. E., 244,260(84) Conway, H. F., 317, 318, 319, 339(491) Cooper, W. C., 144, 195(3b) Corley, C., 280, 296,331(162) Corn Products Co., 411,412,423(1046), 424( 1061) Corrie, J. E. T., 50, 135(111) Costa, D., 313, 338(455) Costillon, L. E., 350, 414(672) Coteron, J. M., 76, 138(196) Cotnoir, L. J., 323,341(572) Cotton, L., 268, 329(67) Cotton, R. H., 400,420(902) Courtaults Ltd., 384, 417(814) Courtonne, H., 317,339(494) Covello, M., 376, 378,417(788) Cowie, J. M. G., 361,415(703) Craig, C. H., 413,426(1124) Craig, H. W., 413,426(1134) Craig, W. L., 324,325,341(574,592,593) Cramer, F., 275, 276, 303,313, 330(117, 125, 137, 138). 338(451) Cramer, W. D., 307, 309,337(409, 410, 423) Crawshaw, J. P., 360,414(693) Crich, D., 186, 187, 199(140) Cronan, C. L., 281,332(188, 190) Cross, W. V., 325,342(606) Crossland, L. B., 405,421(965) Cruzado, C., 20, 21, 22, 26, 32, 33, 34, 35, 36,56, 81, 98, 99, 102, 103, 129, 134(36, 68). 142(348) Cuatrecasas, P.. 202,203, 204, 258(12, 22) Cude, A., 67, 137(149) Cui, C., 63, 137(147) Cunningham, M., 253,260(102) Curtis, R. D., 20, 134(33) Curtis, R. E., 24, 27, 30, 134(39) Cusack, P. A., 17, 133(5) Cushing, M. L., 325,342(605)

AUTHOR INDEX

432

Czaja, A. T.,284.326,332(200), 342(621),

384,417(808) Czernecki, S., 106,141(291), 143, 162, 163, 165, 166, 167.169, 177,187,188,190, 197(68,71.74, 78,79,95), 199(145) Czetsch Lindwald, H., 308.337(421) D Da Silva, E., 106, 141(290) Dahle, L. K.,407,408,422(991) d’Alarcao, M.,52,63, 136(124) Daniel, J. R., 148,149,196(39-41) Danishefsky, S. J.. 32,33,74, 79,84,87,

101,106,116,118,127,128,129. 134(64), 138(180, 182,210,211), 139(248), 140(259), 141(292,319), 142(343-346) D’Appolonia, B. L., 400,403,420(911). 421(933) Das, B.,31 I , 338(445) Das, S. K.,77,138(197) Dasgupta, F., 49,50,56,61,63,81, 135(109), 139(232) Daun, H.,403,421(938,939) Davey, W. S.,405,421(964) David, S.. 17, 24, 29,30,32,35,36,44.45. 48,49,50,51, 55, 62,72,73,74. 75. 80. 104,113,116,117,123,133(2,3,7), 134(43,59,63),135(76,80), 137(172). 186,187,198(132, 133,135) Davies, A. G.,24, 25,27,29,30,32, 134(40, 52,62) Davies, G. M., 106,141(293) Davies, R. F.,325. 341(595) Davis, B. J., 206,232,235,258(29) Davis, E.A., 403,421(946) Davis, N. J. 51,75, 77, 136(113) Davis, R. S., 162,163,165, 197(69) Dawes, H.M.,25,27.30. 134(52) De, H.N., 2%,333(258) de Groot, P. W., 304,306,315,321, 336(392), 338(476) de la Gueriviere, J. F., 388,391,418(855) de la Pradilla, R. F.,83, 102, 139(246) De Leo, T.,296,332(227) De Marco, M. R.,2%,332(227) de Roquefeuil, C..319,339(513) de Ruiter, G.A., 73, 137(176) de Sennyey, G.,36, 104,135(80)

de Wildt, J., 79, 139(222), 173, 197(86) de Willigen, A. H. A., 304,306,315,321,

336(392), 338(476) de Willigen, A. M. A., 316,339(484) deBear, J. S.,86, 100. 140(256) DeBrosse, C.W., 239,260(83) Decheng, S.,326,342(631) DeCrescenzo, G. A., 104, 140(268) Defaye, J., 177, 197(90, 92), 242,259(46a) Deibner, L.,2%, 333(238) Delage. M.M.,303,336(377) Delauney, A., 319,339(513),405,

421(962) DeMesrnaeker, A., 187,188,189,199(144) Dernoussy, M.E.,322,340(554) den Drijver, L.. 36,84,98,135(81) Dengate, H.N.,387,418(843) Denham, F. H..411,423(1047) Denhart, D.J., 79,106,118,138(210) Denn, H.,307,337(413) Denniston, R. H.,376,417(785) Depezay, J. C., 112,113,121.141(298,299,

301) Derksen, J. C., 303,336(372) Dermelj, M., 2%,334(285) Dernikovic, B.,412,424(1078) Descotes, G.,33,86, 134(71) Dessinges, A., 124,125,142(325) Detroy, R. W.,411,424(1052) Deulin, V. I., 280,315,331(179), 338(475) Deutsche Hydrierwerke A,-G., 350,

414(670) Devereaux, J. A., 402,420(918) Dhar, N. R., 272,329(86) Diakun, K. R., 255,261(307) Diaz, Y.,158,197(63) Dickey, S.,44.48,135(97) Diehl, H.,2%. 333(254) Diewald, J., 367,416(734) Dimmick, R. A.,280.2%. 331(162) Dimpfl, W. L., 346,414(651,652) Dinh-Nguyen, N., 392,419(859) Dische, Z., 209,212,259(39) Dittmar, F.,321, 340(546) Dixit, S.,78, 138(208) Dlask. V.,296,333(239) Doane, W.M.,327,343(648) Dobry, A., 408,422(993) Doerr, P., 206,232,258(28) Doganova-Koleva. L.,320,340(534)

AUTHOR INDEX Doi, K., 410, 423(1023) Domazetis, G., 25, 134(49) Domingo. L. R., 115, 122, 141(313) Domingos, A. M., 25, 134(54) Dominguez-Dalda, M., 76, 138(196) Donelson, D. H., 404, 421(954) Donnerstag, A., 73, 137(173) Donninson, G. H., 316, 339(482) Donovan, J. W., 393, 400,419(861, 861a) Dornhagen, J.. 104. 140(273) Douwes, M., 54, 65, 136(136) Doyle, R. J., 408, 422(1003) Drapron, R., 303, 336(374) Dreef, C. E., 82, 83, 139(236, 237) Dreher, K. L., 202, 225, 233, 239, 242, 258(3), 259(64), 260(82) Drotschmann, C., 321, 340(542) Drzewinska, E., 413, 426(1122) Du, M.-H., 73, 137(177) Du Chatelier, G. G., 297, 334(298) Dubina, L. G., 384,418(820) Duckova, K., 351, 359, 414(675) Dudacek, W. E., 411, 424(1056) Dugandzic, M., 319, 340(525) Dumanskii, A. V.. 300, 309. 311, 335(340-342) 337(433). 360,361, 4 15(694) Dumanskii, 0. A., 311, 338(442),360, 415(695) Dumpert, G., 274, 330( 107) Dunning, H. N., 388, 389,418(849) Dupradeau, F.-Y., 73, 104, 137(178) Dupuis, J., 154, 187, 188, 196(54). 199(143) DurCault, A., 112, 113, 121, 141(298, 299, 301) Durette. P. L.. 178, 197(96) Durieux, O., 327, 342(633) Dushenko, V. P., 301, 336(360) Dushev, A,, 317, 339(498) Duynstee, H. K.. 79, 102, 103. 117, 139(218) Dvornik, I., 325. 342(604) Dwonch, W., 275, 330(118) Dykyj. J., 265. 317. 328(44), 339(489)

433

Edwards, F. C., 265,266, 303, 329(49) Edwards, F. W., 268, 329(59) Efrenova, A. N., 327,342(640) Egorov, G. A., 304, 337(395) Eichler, E., 174, 197(88) Eis, M. J., 79, 138(214) Eisen, H. N., 201,202,258(1) Eisner, H., 293,332(226) Ekburg, T., 76, 97, 138(193) El Khadem, H. S., 16 El Laghdach, A., 158, 159, 197(63,64) Elder, A. L., 310,338(437) Elgal, G . M., 402,420(916) Eliassaf, J., 281,296,332(192), 334(274) Eliasson, A. C., 396, 397,398,399,400, 419(866, 887), 420(894) Elie, C. J. E., 82, 83, 139(236, 237) El-Khawas, F., 308,337(421) Ellms, J. W., 272, 329(89) El-Mashatt, N., 298,335(322) El-Shenaway, H. A., 73, 137(171) Elsken, R. H., 302,336(362) El-Sokkary, R. I., 72, 117, 137(159), 141(320) Emery, A. N., 409,410,422(1013) Engvall, E., 249, 260(94) Entrekin, D. N., 305, 337(396) Epley, J. D., 244, 260(84) Erikson, M. S., 204, 225, 229, 242, 258(26), 259(64) Erlander, S. R., 319,321,339(516), 360, 414(690) Erleau, B. H., 325,341(595) Ernback, S., 202, 204, 258(13) Ernst, B., 187, 188, 189, 199(144) Ernst, L., 272, 330(94) Esko, J. D., 106, 141(285) Esnault, J., 104, 107, 108, 140(267) Euler, H., 265, 274,279,328(39), 330(104), 331(153) Evans, I. D., 322, 340(560), 375, 404, 417(778), 421(953) Evans, J. W., 324, 325, 341(575, 598) Evans, T. H., 412,424(1070)

E Eaton. F. J., 265, 328(40) Eberius, E., 311, 338(441) Edelman, G. M.. 234,260(75) Edgar, K. J.. 19, 80. 123, 133(10)

F Faber, J. A., 413, 425(1119) Fabry, S., 268, 329(60) Fadeev, G. N., 265, 328(37)

434

AUTHOR INDEX

Faerman, G. P., 272,329(87) Falck, J. R., 83,105,139(243), 140(279) Faller, A., 188,lYY(148) Fan, L.T., 307,337(412) Fapojuwo, 0. O., 409,411,422(1004) Farbenfabriken Bayer A.-G., 326,342(627) Farkas, V., 131,132,142(352) Farr, A. L.,232,238,239,251,260(74) Farrow, E., 304,336(387) Fauq, A. H., 83,139(240) Favor, H. H., 405,421(96.5) Favretto, L.,319,340(526) Feather, M. S., 4 Federowicz, M.,357,360.414(689) Fedotova, L. J., 406,407,422(984) Fehlhaber, H. W., 73,137(173) Feldman, M., 279,331(156) Feldmann, G., 403,421(932) Feldmann, J., 182,198(98) Fellers, C., 411,424(10.53) Feng, T.Y., 296,334(293) Fernandez, C., 113,114,121,123,141(304) Fernandez. P.,52,76,97,117,136(119) Fernandez-Mayoralas, A., 51, 52,55, 56,65,

70,76,136(114,118,142). 138(196) Ferro, V., 74,137( 179) Fetzer, W. R., 308,309,337(420) Fickweiler, E., 145,195(16) Field, E., 264,268,328(24) Field, J . 11, 269,296,329(71) Filippova, R. L., 410,423(1020-1022) Findley, A., 322,340(.550) Finstad, H., 398,399,419(887) Firth, J. B., 26.5,328(41) Fischbach, E. R.,308,337(417) Fischer, H., 154,196(.54). 376,417(782, 783) Fischler, F., 319,339(521) Fishel, C. W., 408,422(1003) Fisher, E. H., 325,341(600) Fisher, M., 74.138(180) Fishwick, M.J., 386,418(821) Fitremann, J., 112, 113,121,141(301) Fleming, 1. D., 278,284,331(146) Fles, M., 388,418(8.50) Flitsch, S. L., 51,75,77,136(113) Flood, E. J., 412,425(1097) Florent, J.-C., 104,105.107,140(269,271) Fodiman, L.V., 325,342(610) Fodor, L., 374,375,416(770) Forchioni. A., 24,30,134(43)

Forry, K. R., 247,260(91) Forsberg, L. S., 202,231,233,239,245,246,

258(3), 260(72, 82,88) Foster, J. F., 264,274,275,276,277,284,

303,328(18), 330(123), 331(141, 144), 332(202, 203) Fourrey, J. L., 186,187,198(122) Fox, J. J., 124,125. 142(326) Fraenkel, B., 326,342(629) Francesconi, L., 293,332(224) Franciotti, M., 104,140(274) Frangou, A., 20,134(32) Franklova, S., 319,339(511) Fraser, J. R., 104,108,140(266). 324, 341(576) Fraser-Reid, B., 52,55, 63,78.82,113,114, 121,123,136(126, 139). 138(202), 141(304), 170,197(84,85) Freedman, S. O., 202,209,249,258(9, 18) Freeman, B., 116,122,141(318) Freeman, F., 186,187,188,198(120, 121) Freeman, M.E., 311,338(444) Freitag, F., 412,426(1095) French, D., 209,214,2.59(38),26.5,266,268, 269,270,272,274,275,280,290,294, 303,329(48, 65,75),330(109, 111). 331(181), 346,347.348,351,355,363, 396,403,404,412,414(653, 6.57). 419(874).421(948),424(1065) Frenzel, H., 148,196(26) Fresenius, R.,293,332(217) Freundenburg, K.,274.330( 107) Frew, T., 83,139(24.5) Freymann, M., 304,306,336(393), 337(406) Freymann, R., 304,336(393) Fricker, A.. 386,396,418(839) Frieden, A,, 404,421(956) Frommherz. T.V., 413,426(1131) Fuccello, A., 148,196(34) Fuehrer, C., 313,338(457) Fuji, T., 367,369,416(740) Fujie, M., 75,138(187) Fujita, K., 117,141(321) Fujita, Y., 126,142(336) Fukagawa, Y., 87,100, 140(260) Fukomori, R., 413,426(1125) Fukuda, T., 374.416(773) Fuller, A. T., 209,259(43) Fuller, C. H., 268,329(67) Fuller, C. M., 296,333(264)

AUTHOR INDEX

Fuller, C. H. F., 280, 285, 296, 331(180), 332(204), 333(245), 334(284) Fumakashi, S., 387, 418(844) Funabashi, M., 78, 138(207) Furneaux, R. H., 70, 105, 137(158), 140(281, 282) Furuichi, K., 186, 187, 198(125) Furukawa, S., 367, 369, 416(740) G

Gabrielsson, K., 397, 419(883) Gagnet, R., 104, 105, 107, 140(269,271) Gahnberg, L., 229. 259(67) Gaillard, T., 386, 387, 418(832) Gainsford, G. J., 70, 137(158). 139(281) Gal, S., 374. 375,416(770) Gallegos, A,, 83, 139(240) Galli, R., 164, 165, 197(72) Gally, J. A., 234, 260(75) Galosi, G., 399, 419(893) Gamayunov, N. I., 301, 306, 336(352), 337(405) Gambazimalayan, V. G., 405,421(961) Ganem, B., 79. 138(214) Ganesh, K. N., 41, 95, 118, 123, 135(85) Ganther, E. H.. 144. 195(5) Gantner, G. S., 283,297,332(198), 334(294, 295) Garatt, D. G., 154, 196(57) Garcia de Maria, C., 296, 333(243) Garcia-Mandoza, P., 163, 164, 166, 197(70, 73) Gardel. S., 403, 421(947) Garegg, P. J., 44. 49, 50, 52, 56, 61, 63, 79, 81, 82. 83. 129, 130, 135(92, lOY), 136(128), 138(215), 139(232), 142(349), 179, 197(97) Garin, L. F.. 326, 342(616) Gaudechon, H., 309,337(431) Gauthier, C., 293, 332(220) Gauthier de Claubry, H., 264, 328(16) Gautner, G. S., 363, 415(709) Gavcr, K. M., 350, 376, 414(671), 417(780) Geckeler, K. E., 327, 343(647) Geddes, W. F., 309, 337(427. 428) Gelas, J . . 177. 197(92) Gelmi. M. L., 126. 142(335) G.E.M.A., 297. 334(302) Gender, M. J., 185, 198(110)

435

Germani, R., 396,400,402, 419(878), 420(909) Gervay, J., 127, 129, 142(345) Gerz, M.. 126, 142(334) Gesellschaft fuer Industrieforschungen und Betriebsversuche, 350, 414(668) Getman, D. P., 104, 140(268) Ghidalia, W., 404, 421(958) Ghosh, R., 77, 138(197) Gibbons, G. C., 412,424(1071) Gibinski, M., 351, 386,414(677) Gidel, A., 303, 311, 336(368) Gidney, M. A. J., 253,260(99, 101) Giese, B., 154, 187, 188,196(54), 199(141-143) Giesecke, F. O., 410,423(1033, 1035) Gigg, J., 69, 83, 137(154), 139(238, 239) Gigg, R., 69, 83, 137(154), 139(238, 239) Gilbert, G. A,, 278,280,285,331(149) Gilbert, S. G., 307,337(413), 403,421(938, 939) Gilges, S., 187, lYY(142) Gill, L. O., 314, 317, 338(465) Gilles, K. A., 280, 296, 320, 331(172), 333(271), 340(539) Gillies, D. G., 20, 21, 24, 25, 26, 33, 34, 134(32. 33) Gilman, S., 184, 191, 198(104, 106) Gilzin, V. M., 406, 422(982) Ginsburg, V., 204, 255, 258(25), 261(106, 108) Ginzburg, A. S., 306, 337(408) Girard, P., 303,311,336(368, 370) Giuliano. R. M., 162, 163, 165, 197(69) Glaudemans, C. P. J., 75, 77, 95, 138(188, 199) Glen, A., 41, 76, 95, 97, 118, 123, 135(86) Click, D., 209, 212, 259(39) Glicksman, M., 209, 242,258(46) Godina, D. A., 272,329(87) Goebel, C. V., 346,414(651) Goebel, W. F., 217, 259(50, 51) Goemoery, S., 410,423(1036) Goerlitz, H., 296, 333(267) Goettsch, H. M., 265, 328(32) Gogjoian, G., 44, 45, 46.48, 135(100) Golal, A. M., 412, 424(1060) Gold, D. V., 253, 261(104) Gold, P., 202, 209, 249, 258(9, 17)

436

AUTHOR INDEX

Goldenberg, N., 285,296, 332(204), 333(245, 264), 334(284) Goldsmith, D., 192, 199(152) Goldstein, I. J., 217, 249, 259(52, 53), 260(94) Golenkov, V. F., 406,422(982) Golovnya, R. V., 411,423(1041) Gonzalez, F., 112, 115, 122, 141(297, 313) Gopalakrishnan, V., 41, 95, 118, 123, 135(85) Gopalsarny, A., 105, 140(280) Gordon, J., 403,421(946) GorC, J., 46, 135(102) Gore, P. M., 77, 138(198) Gorelkina, T. M., 296, 334(275) Gorrichon, L.. 105, 106, 107, 140(272) Gorski, L., 411,424(1049) Goshirna, G., 396,419(876) Goto, T., 327, 342(639) Gottlieb, H. E., 127, 142(340) Gottschield, H., 393, 400, 419(860) GOU,D.-M., 52, 56, 63, 82, 136(125, 143) Cough, B. M., 317, 339(492) Cough, G. R., 85, 140(256, 257) Granger, P., 20, 133(30) Granskaya, T. A., 299, 335(336) Grasselt, H. M., 412, 424(1088) Gray, G. R., 204, 258(24) Gray, V. M., 368, 369, 376,416(747) Grebaut, J., 388,391.418(855) Green, J., 47, 135(104) Greenwood, C. T., 264, 270,280, 281, 282, 286, 296, 304, 313, 328(9, 14). 329(74), 332(183,185,195, 206), 333(260,269), 336(385), 346, 359, 361, 415(703) Grice, P., 19, 44, 46, 49, 51, 111, 115, 116, 121, 122, 133(12, 13) Grieco, P. A., 184, 191, 198(102, 104-106) Griessmayer, V., 296, 332(229) Griffith, D. A., 127, 129, 142(345) Grinberg, V. Ya., 406,407,408,422(984, 985, 989, 990) Grindley, T. B., 17, 19, 20, 22, 24, 25, 27, 28, 29, 30, 31, 32, 35, 36, 37, 38, 49, 50, 51. 54, 56,61, 62, 63, 66, 67, 68, 69,70, 81, 96, 98, 101, 103, 113, 114. 123, 124, 131, 132, 133(6, 19-21), 134(33, 37-39, 41, 42, 44. 60), 135(82, I l O ) , 136(145, 145a, 145b. 145~).137(149, 151). 139(23I), 142(351)

Groneberg, R. D., 73,80,137(160) Groninger, K. S., 187, 199(142) Grossfeld, J., 326, 342(617) Grouiller, A., 33, 86, 134(71) Gryuner, V. S., 402, 411,412,420(920), 424(1055) Guggolz, J., 296, 333(255) Gugliemelli, L. A., 327, 343(648, 649) Guilbert, B., 51, 75, 77, 136(136) Guilbot, A., 303, 311, 336(368, 370, 374), 402,420(913) Gumayunov, N. I., 301,336(351) Gunatilka, A. A. L., 186, 187, 198(137) Gundrum, L. J., 296, 334(278) Gunther, H. H., 144, 195(3c) Gupta, G. N., 322, 326, 341(564) Gupta, K. K. S., 280, 331(163) Gupta, S., 301, 336(167) Gupta, U. K. S., 280, 331(163) Gurjar, M. K., 44,78, 79, 82, 98, 127, 135(98, 99). 138(204,209, 212), 139(233), 142(341) Guryanov, V. E., 412,425(1099) Guthrie, J. D., 317, 339(497) GutiCrrez, C. G., 44,45, 46, 48, 135, 135(100)

H Haas, R. H., 303, 336(380) Hach, R. J., 275, 303, 330(129) Hadzijev, D., 302, 336(366), 388, 390, 393, 394,395,418(851), 419(862) Hain, V., 303. 336(376) Haines, A. H., 41, 135(89) Haisman, D. R., 404, 421(953) Hakomori, S., 253, 261(103) Halban, I. H., 293, 332(226) Halcomb, R. L.. 79, 106, 118, 138(210, 211) Halick, J. V., 296, 333(266) Hall, N. C., 253, 260(102) Haller, R., 264, 265, 317, 328(7, 28.45). 339(488) Hallgren, W., 266, 329(53) Hamano, S., 413,425(1110) Hammarstrom, S., 249, 260(94) Hampel, G., 397. 405, 419(881), 421(975) Hanajima, M., 35, 36, 53, 54, 55, 75, 77, 84, 105, 114, 123, 135(77) Hancock, R., 209,259(41)

AUTHOR INDEX Handa, T., 268, 275, 283, 286, 290, 329(61), 330( 131) Handlii, K., 25, 134(46) Hanes, C. S., 274, 330(108) Hanessian, S., 17, 30. 85, 105, 133(3), 140(251, 276) Haney. H. F., 400.420(902) Hanna, I., 106, 141(288) Hannah, T. G., 418(847) Hansen, L. M., 403,421(949) Hanson. T. P., 307, 309, 337(409, 423) Haque, M. E., 33, 53, 55, 64,75, 77, 81, 84, 85, 105, 106, 110, 117,118, 134(70), 136(130, 131). 296, 333(258) Harada, K., 87, 140(261) Harada, S.. 375. 417(777) Harris, R. H., 319, 339(514) Harris, R. K., 25, 29, 134(56) Harris, W. A,, 400, 420(902) Harrison, W., 264. 265. 328(21-23) 372, 416(7S6) Hartley, O., 70, 137(158) Hartmann, J., 373, 416(767) Hasegawa, K., 78, 87, 138(206), 140(261) Hasenkamp, P., 410,423(1034) Hashimoto, H., 104, 105, 140(275,283) Hass, R. 9.. 359, 414(688) Hassid, W. Z., 296, 334(277) Hassner, A., 162, 197(66) Hatch, G. L., 280, 331(171) Hauser, S. J., 272, 329(89) Hawley, R. L., 410,423(1030) Haworth, W. N., 296, 334(281) Hayakawa, A., 374, 375,417(775) Hayakawa. T., 296, 333(257), 334(273) Hayakawa, Y.,185, 198(111, 112) Hayes, M. L., 133, 142(354) Heath, D.. 411,424(1057) Heftmann, E., 202, 258(11) Heiker, F.-R., 85, 140(250), 182, 198(98) Heininger, J., 367, 415(725) Heintz, R. M., 104, 140(268) Heisman, D. R., 322, 340(560) Hellerqvist, C. G., 212, 258(48) Hellman. N. N., 301, 306, 309, 311, 312, 336(359), 337(425), 338(440) Helm. R. F., 54, 55, 67, 68, 69, 70, 105, 106, 131, 136(132) Hemscheidt, T., 19, 113, 133(14) Henglein, M., 313, 338(451)

437

Henkel et Cie, 322, 325, 340(553, 558), 341(591) Hennig, H. J., 318, 339(508) Henon, M., 405, 421(962) Henry, G., 186, 187, 198(122) Herbst, W., 275, 330(117) Hering, A., 322, 340(559) Hermann, Z. E., 325, 342(604) Hermansson, A,, 410, 423(1026-1028) Hernadi, S., 412,425(1092, 1093) Hernandez Mendez, J., 296, 333(243) Hernandez-Mateo, F., 163, 164, 166, 197(70,73) Herradon, 9.. 19, 133(15-17) Hertel, R. H., 408, 422(995) Herzig, J., 127, 142(340, 342) Herzig, Y., 126, 142(339) Hess, K., 373,409,416(763-765), 422(1009) Hester, E. F., 402,403,420(922) Heyns, K., 182, 198(98), 321, 340(543) Hibara, J., 374, 416(773) Hibi, Y., 386, 387, 388, 418(840, 846) Hidi, P., 402,420(917) Hiemstra, P., 298, 323,335(326), 341(568) Higginbotham, R. S., 278, 280, 282, 331(148, 169), 373,416(768) High, R. L., 296, 334(287) Hilbert, G. E., 278,331(150), 357,363,386, 414(687), 418(824) Hilbert, G. H., 396,419(875) Hilbert, H., 412,424(1070) Hill, J. R., 325, 342(609) Hill, R. D., 393,419(863) Hills, 9. P., 302, 336(364) Hills, J. P., 360, 414(693) Hindsgaul, O., 52,75, 136(116) Hirabayashi, T., 413,425(1110) Hirai, A., 303, 336(371) Hirano, J., 274, 330(116) Hishino, M., 409,422(1010) Hixon, R. M., 278, 331(147), 369, 371, 416(752) Hizukuri. S., 284, 332(199) Hizukuri, Z., 296, 333(270) Hobert, K., 73, 137(173) Hobson, P. N., 280,331(165) Hodge, J. E., 411,424(1052) Hodosi, G., 33, 81, 125, 126, 127, 131, 133, 135(73), 139(230), 142(327) Hoehn, M., 319, 340(529) Hoekstra, W., 186, 187, 198(139)

438

AUTHOR INDEX

Hoelzl, J., 296, 333(238) Hoffgen, E. C., 85, 140(255) Hoffman, P., 187, 188, 189, 199(144),413, 426( 1134) Hoffmann, G., 301, 336(361) Hoffpaiur, L. C., 317, 339(497) Hofstee, J., 381,417(804) Hohnen Oil Co., Ltd., 413,426(1130) HoleEek, J., 25, 134(46, 47) Hollo, J., 264, 274, 275, 276, 277, 279, 280, 281, 282, 283, 292, 293, 295, 296. 297, 322,323,328(15), 330(112, 119), 331(157-160, I&), 332(186, 196, 198). 333(263), 334(294,295,299), 341(565), 363, 374, 375,415(709), 416(770) Holm, J., 400,420(894, 895) Holm, Y., 393, 400, 419(861b) Holme, J., 397,419(882) Holmes, D. S . , 77, 138(198) Holmes, M. J., 373, 416(762) Holt, F., 412,424(1082) Holzapfel, C. W., 19, 25, 27, 28, 30. 32, 33, 35, 36, 49, 51, 55, 68, 69, 71, 77, 80, 84, 87, 96, 97, 98, 102, 103, 106, 131, 132, 133(18), 134(51), 135(72, 81), 136(140), 141(289), 142(350) Homberger, E.. 378,382,417(794) Homirovic-Culjat,J., 406, 422(981) Hong, N., 78, 104, 138(207), 140(275) Honshu Paper Co., Ltd., 413, 425(1118) Hood, L. H., 322,323, 341(566) Hoodless, R. A., 324, 341(576) Hoover, R., 302,336(366), 388, 390, 393, 394,395,418(851), 419(862) Hoper, R. D., 396,398,419(869) Horii, F., 303, 336(371) Horisaki, T., 112,141(296) Horowicz, Z.. 351,414(676) Horton, D., 144,159, 180, 195(la), 197(65), 198(97b) Horvat, P., 399, 419(893) Horvath, R. F., 74, 138(180) Hoseney, R. C., 404,421(952) Hoshino, Y., 288, 332(212) Houben-Weyl, 144, 195(3a) Houf, W. H., 412,424(1062) Hoult, R. E., 413, 425(1109) Howard, N. B., 397,419(882) Howe, T. J., 105, 140(280) Hsieh, Y.-C., 277, 286, 331(142)

Hsu, K. H., 277, 286, 331(142) Hu, S. H., 74, 101, 106, 138(182) Huckstep, M. R., 187,188,199(147) Hudson, C. S., 280, 331(182) Huebner, J., 268, 269, 270, 279,296, 313, 322,329(69), 340(556), 378,383, 417(796) Hug, P., 187, 188, 189. 199(144) Hungate, R., 32, 33, 134(64) Hunt, K., 226, 259(66) Hursthouse, M. B., 24, 25, 27, 29, 30, 134(40,52) Hurwitz, 0.. 324, 341 (581) Husbands, J., 410,423(1029) Huszar, J., 322, 323, 341(565) Hutson, D. H., 144, 195(la) Huyser, J. J., 33, 135(72)

I Iacobucci, S.,52, 63, 136(124) Ichikawa, Y., 55, 66, 136(141), 137(148) Iga, K., 399,419(889) Igaue, I., 296,333(257), 334(273) Ignatev, V. P., 296, 333(242) Ignateva, N. K., 281, 332(193) Iida, Y., 413,426(1136) Ike, A. F., 305, 337(396) Ikeda, K., 186, 187, 198(136) Ikeda, M., 327,342(639) Ikota, N., 86,140(258) Iliescu, G., 413,425(1104) Imam, S . H., 406, 422(983) Imberty, A., 266, 267, 303, 329(51, 52) Imeson, A., 411. 423(1043) Inoue, H., 410, 423(1019) Inoue, Y., 84, 139(249) Insinski, Z., 413, 425(1107) International Minerals and Chemical Corp., 322, 341(563) Inveresk Paper Co., 326,342(620) Irgolic, K. J., 148, 149, 196(42) Irklei, V. M., 303, 336(378), 359, 374 Isac-Garcia, J., 163, 164, 166, 197(70, 73) Isenberg, I., 287, 288, 293, 332(209,211) lshikura, T., 87, 100, 140(260) Ito, M., 280, 331(173, 177) Ito, R., 185, 198(112) Ito, T., 327, 343(646)

439

AUTHOR INDEX Ito, Y.,66, 69, 71, 76, 97, 126, 137(150), 138(194), 186, 187, 198(138) Itoh, N., 326, 342(619) IUPAC-IUB Commission on Biochemical Nomenclature, 202, 258(4) IUPAC-IUBMB Nomenclature of Carbohydrates, 144, 195(lb) Ivanov, N., 296,333(253) Ivekovic, H., 316, 339(479) Iversen, T., 44, 135(92) Iwabuchi, Y., 73, 80, 137(160) Iwaki, R., 373,416(761) Iwanowski, W., 374,416(769) Iwasaki, I., 313, 327, 338(461), 342(635) Iwasaki, T., 413, 426(1135) Iwase, F., 412, 424(1063) Iyer, R. N., 217, 259(52, 53) Izquierdo Cubero, I., 84, 98, 139(247)

J Jackman, L. M., 239, 260(83) Jacquelain, W. A,, 264, 328(19) Jacquinet, J.-C., 70, 72, 96, 106, 137(155, 161), 140(284) Jacqumain, D., 304,336(394) Jadzyn, B., 296, 333(240) Jaekko, E., 325,342(608) Jagodzinski, W., 327,342(637) James, B. D., 25, 134(49) James, W. J., 346,347, 414(653) Jane, J. L., 317,319, 339(499, 500). 357, 360, 372, 402, 404, 414(685), 416(755), 420(926), 421(955) Jankowski, K., 186, 187, 198(128) Jansson, P. E., 245, 260(85) Jansze, J.-P., 82, 139(236) Jaramillo, C., 116, 122, 141(318) Jarovenko, W., 413,425(1102) Jarvis, D. A., 400,402, 420(910) Jasiunas, R., 321, 340(548) Jaurand, G., 73, 104, 107, 108, 137(163), 140(267), 154, 156, 186, 187, 196(60), 198(124) Javora, P. H., 148, 149, 196(36) Jaw, J. Y.,184, 191, 198(102) Jeanes, A., 209,259(44) Jedrzejak, M., 411, 424(1049) Jeffrey, A. M., 204, 258(25)

Jenkins, D. J., 42, 49, 50, 63, 68, 69, 135(91), 137(152) Jennes, R., 280, 331(172) Jennings, H. J., 73, 137(164) Jensen, B. N., 388,396,397,398,418(853) Jerian, E., 281, 332(194) JimCnez-Barbero,J., 52.76, 97, 117, 136(119), 138(196) Jiravek, V., 146, 1%(24) Joglar, J., 74, 138(180) Johansen, R. G., 398,411,419(885) Johansson, B. G., 249,260(94) Johansson, J. A. O., 297,334(305) Johnson, J. A., 405,412, 421(968), 424(1060) Johnson, J. M., 403,421(946) Jonas, L., 2%. 332(228) Jones, J. K. N., 226,259(66) Jones, R. L., 324,341(588) Jongh, G., 396,419(873) Jordan, W.,364,415(715) Jorgenson, B., 349,414(667) Joslyn, M. A., 327,342(643) Jouin, P., 186, 187, 198(122) JouIIiC, M. M., 153, 196(53) Jutten, P., 104, 140(273)

K Kaburagi, T., 49, 135(108) Kacmarski, M., 360,415(696) Kadera, Y.,373,416(759) Kagitani, T., 366, 415(711) Kahne, D., 79, 126, 127, 139(221) Kajiura, T., 275, 286, 330(131) Kalashnikov, I. A., 402,411,412, 420(920), 424( 1055) Kale, N. R., 412, 424(1066, 1072) Kaluza, Z., 169, 197(79) Kamerling, J. P., 76, 138(192) Kaminskii, L. P., 301, 336(360) Kamiyashi, K., 306, 337(406) Kamogawa, S., 363,415(710) Kanauchi, Y., 296, 333(257) Kane, J. A., 212, 251,258(48), 260(96) Kane, P. D., 186, 187, 198(119) Kanemitsu, K., 33, 35, 36, 49, 53, 54, 55, 64, 65,75, 77, 84, 105, 106, 110, 114, 117, 123, 134(70), 135(77, 106) Kaneniwa, N., 381,417(799)

440

AUTHOR INDEX

Kanie, 0.. 76, 97, 138(194) Kano, T., 387,418(844) Kantor, L. T., 44,45, 46,47, 135(101) Kaper, J. A. G., 302,336(363) Kapp, M., 402,420(919) Karakawa, W. W., 202,232,250, 251, 258(15), 260(96, 97) Karp, G. W., 384,417(811) Karpova, I. F., 313, 338(456) Karrer, P., 324, 341(581) Karve, M. S., 412,424(1066) Karzownik, B. A., 309,337(434) Kasa, N., 25, 29, 134(55) Kassenbeck, P., 409,422(1007) Katano, K., 126, 127, 142(330) Katayama, M., 265, 328(38) Kato, T., 413, 426( 1133) Kattein, A,, 309, 337(430) Katz, J. P., 318, 319, 339(508, 509) Katz, J. R., 303, 308, 317,336(372, 373), 337(419), 339(493), 384, 417(812) Katzbeck, W. J., 265, 270, 284, 328(47), 332(201), 361, 362,415(700) Kawa, M., 105, 140(283) Kawamura, A., 320, 326, 340(540) Kawase, Z., 296, 334(282) Kaye, A., 155, 156, 188, 196(61), 199(150) Kazakov, E. V., 313,338(456) Kearsley, M. W., 323, 341(573) Keck, G. E., 186, 198(116) Keinan, E., 127. 142(342) Keller. J., 202, 258(21) Kelly, S. A., 208, 219, 230, 246, 253, 254, 259(36), 260(89) Kemne, L., 253, 260(100) Keneaster, K. K., 296,333(266) Kenne, L., 245, 260(85) Kennedy, J. D., 19, 26, 34,35, 133(25), 134(58) Kennedy, J. F., 365, 415(718) Keogh, W. J., 398,411, 419(885) Kerinan, E., 127, 142(340) Kerr, K. W., 412,424(1074-1076) Kerr, R. W., 265,270, 284, 326,328(47), 332(201), 342(613), 361, 362, 369, 415(700-702) Kertesz, M., 275, 330(126) Kessler, H., 126, 142(334) Khan, K. M., 281, 332(185) Khan, S. H.. 255, 261(107)

Khare, A., 78, 138(208) Khare, N. K., 78, 138(208) Kharin, S. E., 321, 340(548) Khegai, T. A., 313,338(452) Khomutov, L. I., 384,418(820) Khorana, H. G., 202,204,211, 258( 14) Kibayashi, C., 112, 141(300) Kiddle, J. J., 83, 139(245) Kiessling, L. L., 52, 61, 75, 77, 101, 103, 136(115), 138(185) Kihara, Y., 296,334(282) Kihlberg, J., 174, 197(88) Kiki, S., 313, 314, 338(454) Kikuchi, K., 413, 426(1128, 1129) Kikuchi, T., 33, 53, 106, 110, 117. 134(70), 136(131) Kildsig, D. O., 303, 305, 336(381), 337(402) Kim, G., 192, 199(154) Kim, H. O., 113,141(305), 275, 330(127), 393,419(863) Kim, I. J., 74, 101, 106, 138(182) Kim, K., 63, 137(146) Kim, K. S., 63, 137(147) Kim, M. H., 113, 141(305) Kim, S. K., 400,420(911) Kim, S.-H., 79, 126, 127, 139(221) Kim, Y. J., 392,419(858) Kimura, K., 185, 198(107), 374, 416(773) Kimura, R., 366,415(711) Kindt, T. J., 229, 244, 260(71, 84) King, H., 309, 337(432) Kingswood, K., 405,421(976) Kirizhnu, A. F., 297, 334(311) Kirkpatrick, W. K., 349,357,414(665) Kishi, Y.,105, 140(278), 177, 197(93) Kislova, T. V.,411, 423(1044) Kitabara, N., 280, 331(176) Kitagawa, I., 84, 139(249) Kitajima, T., 116, 141(317) Kitamaru, B., 303, 336(371) Kitamura, S., 387,388,418(846) Kitamura, T., 413, 425(1112) Kiyoshima, K., 87, 100, 140(260) Kjaer, A., 188, 199(151) Kjolberg, O., 18,78, 82, 98, 133(9) Klayman, D. L., 144, 195(3c) Klein, G. H., 412, 424(1064) Klein, R. S., 124, 125. 142(326) Klenha, J., 146, 196(24) Kleppe, K., 208, 215, 259(32,34)

AUTHOR INDEX Klimek, D., 361, 414(691) Klotz, L. J., 327, 342(641) Knapp, D. W.. 209, 214. 259(38) Knapp, S., 114, 116, 122, 141(306, 318) Knauss, C. J., 292, 295, 332(214) Knightly, W. H.. 396, 419(879) Knowles, J. R.,167, 197(75) Knull, H., 211, 219, 258(47), 259(57) Knyaginichev, M. I., 319, 320, 339(512), 340(532) Kobamoto, N., 378, 417(797) Kobayashi, M., 79, 139(216, 217) Kobayashi, T., 49, 53, 54, 64, 65, 84, 105, 106, 114, 135(106), 278, 280,331(151, 174) Kober, H., 321, 340(546) Kobzeva, A. A., 410, 423( 1022) Koch, K., 69, 103, 137(153) Kochan. D. A., 411. 424(1056) Kochetkova, Z. V.. 374, 416(772) Kocienski. P., 186, 188, 198(117), 199(148) Kocourek, J., 146, 196(24) Koda, N.. 312, 338(449), 346, 353 Koedding, D., 398, 411,419(885) Koekemoer, J. M., 19, 25, 27, 28, 30, 32, 35, 36. 49, 51, 55. 68. 69, 71, 77, 80, 84, 87, 96, 97, 98, 102, 103, 133(18), 134(51), 135(81), 136(140) Koeman, F. A. W., 76, 138(192) Kohara, K., 413, 425( 1103) Kohata. K., 75, 138(189) Kohler, G., 202. 258(7) Koizumi, H., 308,337(418) Koizumi, N.. 303, 306, 311, 336(369), 337(403,404) Koizumi, S., 413, 425(1116) Kokini, J. L., 308, 337(417), 360 Koller, W. D., 386. 396, 418(839) Kolodynska, U.,296, 333(241) Kolomeirseva. I. V., 296, 333(242) Kolpakova. 1. D., 303, 336(378), 359, 374 Kolthoff, I. M., 272, 329(88) Komandin, A. V., 298, 335(327) Komarova. B. I.. 411, 423(1048) Kondo, N., 364,415(715) Kong, F., 19, 77, 78, 80, 81, 96, 133(11), 138(203) Kong, X., 19, 22, 30, 31, 32, 36, 38, 56. 113, 114, 123. 124. 133(19-21), 134(37), 135(82)

441

Konishi, S., 413, 426(1133) Konishiroku Photo Ind. Co. Ltd., 296. 334(292) Konitz, A., 313, 316, 338(459) Konrad, G., 384,417(816) Konradsson, P., 170, 197(84, 85) Kooi, M., 270, 296, 329(79) Kopper, S., 24, 134(45) Koptelova, E. K., 322, 340(552) Korchagina, E. P., 384, 418(820) Koricanac, Z., 319.340(525) Kornfield, R., 202, 258(21) Kornfield, S . . 202, 258(21) Korolev, Yu. N., 297, 335(319) Korotchenko, K. A., 326,342(616) Korovkina, E. G., 297, 335(319) Korth, H. G., 154, 187, 188, 196(54), 199(143) Koseki, K., 127, 129, 142(345) Kosemura, S., 78, 138(206) Koshkin, V. M., 301, 336(351) Kostenyuk, N. N., 360,415(695) Kosuge, Y., 44.45, 135(95) KovBE, P., 19, 33, 75, 77, 80, 81, 95, 123, 125, 126, 127, 131,133, 133(10), 135(73), 138(188, 199), 139(228. 230). 142(327) Kovalev, V. V., 297,335(315) Kovalevskaya, E. I., 413,425(1105) Kozaki, Y., 410, 423(1019) Kozikowski, A. P., 83, 139(240, 245), 154, 166, 185, 196(58, 59), 198(108) Kozyrod, R. P., 186, 198(115) Kralovic, J., 67, 137(149) Kramer, H., 376,417(784) Krankkala, P. L., 413,425(1119) Krantz, M. J., 221, 259(61) Krasse, B., 229, 259(67) Krause. A., 327,342(637,638, 642) Krause, R. M., 229, 259(69, 70) Krebs, H., 367,416(734) Krishner, K. K., 253, 260(102) Krochmal, F., 327, 342(637) Kroczak, W., 411,424(1049) Krog, N., 388, 392, 395, 396, 397, 398, 418(848, 853), 419(859, 864, 867) Krogman, C., 99, 140(262) Kruger, G. J., 25, 27, 28, 30, 36, 84, 97, 98, 134(51), 135(81) Kruger, L. H., 322, 341(561)

AUTHOR INDEX

442

Krupey, J., 202, 209,249, 258(18) Krutyi, Ya. R., 297, 335(315) Kruyt, H. R., 299, 320, 335(338), 340(535) Krylova, V. V., 410,423(1031) Kubrick, R. L., 225,242,259(64) Kuchikata, M., 316, 339(483) Kudelska, W., 150, 196(45) Kudla, E., 268,303,320,329(62), 336(379), 386 Kudo, M., 296, 333(257) Kuester, F. W., 264,328(20) Kuge, T., 272, 273, 275, 280, 281, 284,303, 306, 311, 329(91,92), 332(184), 336(369), 337(404), 347. 350, 351, 353, 354. 355, 357, 359, 360, 363, 365, 366, 367, 371, 373, 386, 387,388, 414(667, 673). 415(726), 416(754), 418(840, 846) Kugimiya, M.. 319, 339(518), 393, 400, 402, 419(861, 861a), 420(928) Kulagowski, J. J., 82, 139(234) Kulkami, V. R., 106, 110,141(286) Kumagaya, T., 411, 423(1038) Kuo, S. S., 296, 334(293) Kurasawa, F., 296, 334(273) Kurasawa, H., 296, 333(257) Kurilenko, 0. D., 349,360,413,414(662), 425( 1105) Kurita, K., 74, 136(184) Kusuda, K., 396,419(876) Kuwahara, H., 413,425(1103) Kuza, H., 316, 339(483) Kuznetsova, N. L., 384,418(820) Kuzuhara, H.. 55, 66, 74, 136(141), 137(148). 138(184) KvarnstrBm, I., 52, 56, 82, 83, 136(128) Kwan, F., 367,416(735) Kwon, 0..74, 101, 106, 138(182)

.I Laakonsen, A,, 20, 133(31) LaFont, D., 167, 197(77) Lagendijk, J., 396,397, 419(880) Lalkgerie, P., 177, 197(94) Lallemand, J.-Y., 106, 141(288) Lambert, J. L., 296. 333(235-237) Lamberth, C., 187, 199(142) Lampe, D., 83, 139(241) Lampitt, L. H., 268,280,285, 296, 329(67), 331(180), 332(204), 333(245, 264), 334(284)

Lancaster, E. B., 307, 317, 318, 319, 337(409,410), 339(491). 396,419(871) Lancaster, P. E., 309,337(423) Lancefield, R. C., 209, 229, 232, 238, 239, 249, 251, 259(42,68), 260(73) Lancelin, J. M., 184, 198(101) Lang, K. W., 403,421(936) Lange, C., 274, 330(100) Langkammerer, C. M., 326,342(624) Langston, S., 49, 50, 51, 53, 61, 68, 69, 72, 77, 96, 97, 101, 103, 135(107) Lansky, S., 270, 296, 329(79) L'Anson, K. J., 400, 402, 420(910) Larner, J., 219,252, 259(56) Larson, B. L., 280,331(172) Larson, K., 392, 397, 400, 419(859, 883), 420(894-896) Lassigne, C. R., 20, 133(29) Laszlo, E., 280, 283, 331(166), 332(198), 363, 415(709) Lau, R., 79, 139(220) Lay, L., 52, 136(121) Leach, H. W., 315, 324,325, 338(478) Lechert, H., 302, 336(365) Lechter, J., 327,342(643) Ledward, D. A., 411,423(1043) Lee, B. J., 113, 141(305) Lee, C., 192, 199(152) Lee, H. S., 412. 424(1080) Lee, J. Y., 87, 140(259) Lee, S. J., 63, 137(147) Lee, Y. C., 221,222, 259(61,62) Lees, P., 411, 424(1057) Leeson, P. D., 82, 139(234) LeGallic, J., 76, 138(195) Legler, G., 177, 197(94) Legrand, C., 303,336(375) Lehmann, G., 145, 195(15), 393,419(860) Lehrman, L., 367,416(737-739) Leigh, D. A,, 41, 76, 95, 97, 111, 115, 118, 120, 121, 123, 135(86,87) Leith, S. J., 388, 418(850) Lelievere, J., 402, 410. 418(847), 421(930), 423( 1029) Lelong, V. M., 409,410,423(1016) Lemieux, R. U., 73, 137(177), 217,259(55) Lemoine, R., 74, 75, 76, 138(183, 195) Lenges, J., 304,336(394) Lemon, I. C., 82, 115, 139(234), 141(310) Lenz, K., 323, 341(570)

AUTHOR INDEX Lesage, L., 85, 140(251) Leskova, R., 297, 335(314) Lesnitzky, A., 367, 416(736) Leszczynski, W., 327, 342(632) Leteux, C., 106, 141(291) Leutner, C.. 280, 331(178) Levin. M., 281, 332(192) Ley, S. V., 19. 44,46, 49, 51, 111, 115, 116, 121, 122, 133(12, 13), 141(310), 144. 192, 195(3g), 199(153) Li, N.-Q., 219, 222, 256, 259(60), 261(109) Liang, J., 19, 113, 133(14) Liang, J.-N., 292, 29.5, 332(214) Liao, W., 75, 76. 77, 80, 81, 138(186) Liao, Y.-H., 296. 333(261) Liddle, A. M., 278, 284, 331( 146) Lietlander, M., 112, 141(295) Liggett, L. M., 296, 333(254) Lim, H., 403. 421(950, 951) Linck, K., 177, 197(90) Lindberg. A. A,, 253, 260(100) Lindberg, B., 52, 56, 82, 83, 136(128), 245, 260(85, 99) Lindquist, B., 367,416(731) Linhardt, R. J., 117, 141(322) Lintner, J. C., 324, 341(580) Liotta, D., 144, 186, 187. 192, 395(3h), 198(114, 139). 199(152) Lipatov, G. V., 407, 422(988) Lipatov, I. S.. 315, 338(474) Lipatov. S.. 309, 315, 337(434), 338(472, 473), 381,407,417(798), 422(988) Liping, Z., 326. 342(628) Lipka, P., 152, 196(46, 51) Lipke. P. N., 255. 261(105) Lippmaa, E. T., 20, 133(26) Liptrik, A., 79, 138(213) Litvinov. M. A., 297. 334(307, 308) Liu, B., 206, 210, 213. 219, 222, 223, 224, 246, 258(30, 33), 259(60, 62, 63), 260(90) Liu, C., 102, 103, 140(265) Liu, H.-M., 35. 36. 49, SO, 51, 54, 56, 57, 81, 115. 123. 135(78) Liu. K. K.-C.. 79. 106, 118, 127. 128, 138(210), 142(343, 344) Liu, Y., 75. 76, 77, 80, 81, 138(186) Liu. Y.-C., 52, 56, 63, 136(125) Liuker, T., 187, 199(141) Liverton, N.. 82, 139(234)

443

Liying, C., 326, 342(628) Ljunger, G., 398,399,419(887) Lloyd, H., 313. 314, 315, 322,338(463) Lo, L., 403,421(945) Lobenstein, M., 378,417(792) Lockhart, T. P., 25, 134(48) Loeb, L. F., 367,416(736) Logue, C. L., 411,423(1045) Lombardi, P., 104. 140(140) Lomic, S., 373, 416(758) Loncin, M., 304, 336(394) Lonn, H., 174, 197(89) Lonza Elektrizitaetswerke und Chemische Fabriken Akt.-Ges., 413, 426(1123) Lorenz, A. W., 272, 329(85) Lorenz, K., 386, 396,418(826) Lottermoser, A,, 265, 279, 328(42,43), 331(154, 155) Lovrecek, B., 412,424(1078) Lowary, T. L., 52,75,136(116) Lowey, J. F., 413,426(1131) Lowry, 0. H., 232,238,239,251,260(74) Low, G. D. A., 405,422(978) Lu, D., 75, 76, 77, 80, 81, 138(186) Lubineau, A,, 74, 75, 76, 138(183, 195), 186, 187, 198(132, 133, 135) Luce, E., 186, 187, 198(128) Luchinat, C., 30, 134(61) Luckow, G., 296,333(247) Lueckenhaus, W., 412,424(1084) Lukacs, G., 124, 125, 142(325) Lukyanov, A. B., 316,339(485) Lumiere, A., 297,334(303) Lund, D. B., 402,420(927) Lundberg, B., 397, 419(883) Lundquist. I., 400,420(894, 895) Lutz, A., 412, 424(1085, 1087) LyEka, A., 25, 134(46,47) Lygo, B., 192,199(153) Lynch, D. L., 323,341(572) Lysenko, Z., 153, 196(53)

M Macchia, D. J., 298,335(323) MacDonald, B., 402,420(912) Machinaga, N., 112, 141(300) Maciejewska, W., 360,361, 384, 415(696, 697), 418(818)

444

AUTHOR INDEX

MacMaster, M. M., 321, 340(544, 549, 396, 402, 410,419(871), 420(924), 423(1024) Maczelka, L., 400,420(904) Maeda, I., 280,306, 308, 331(176), 337(407) Maga, J. A., 409,411,422(1004) Magdzik, S., 413,425(1107) Magee, R. J., 25, 134(49) Magidson, 0. Yu.,297, 334(301) Magnusson, G., 52, 54, 70,72, 75, 76, 96, 97, 101, 103, 136(120, 134), 138(190, 193) Maguire, R. J., 113, 141(303) Mahajan, R., 78, 138(208) Maier, H. G., 350, 351, 352, 354, 365. 366. 367, 372, 373, 414(674) Mainkar, A. S., 78, 138(209) Maj, Z., 413, 426(1139) Majmin, R., 349, 408,414(666), 422(997) Malfitano, G., 299,335(337), 400,420(905) Mallet, A., 192, 199(157) Mallet, J. M., 118, 141(323), 192. 199(155-157) Maloisel, J.-L., 129, 130, 142(349) Malyshev, N., 319, 340(530) Manavu. R. M., 49, 53, 135(105) Mandak, M., 351, 359,414(675) Manders, W. F., 25, 134(48) Mandi, A., 280, 331(166) Maneschi, S., 326, 342(623) Mann, J., 186, 187, 198(119) Manners, D. J., 277, 278, 284, 331(143, 146) Mannich, C., 323, 341(570) Manning, D. D., 52, 61, 75, 77, 101, 103, 136(115), 138(185) Manor, P. C., 303, 336(383) Mantick, N. A., 85, 140(257) Marais, C. F., 19, 25, 27, 28, 30, 32, 35, 36, 49, 51, 55, 68, 69, 71, 77, 80, 84, 87, 96, 97, 102,103, 133(18), 134(51). 136(140) Maranduba, A., 75, 76, 138(191) Marchetti, N., 202, 209, 213, 214, 242, 245, 255, 256, 258(10), 259(37, 49), 260(87) Marchis-Mourens, G., 409,423(1017) Marco, J. A., 112, 115, 122, 141(297, 313) Marco-Contelles, J. L.. 113, 114, 121. 123, 141(304) Marecek, J. F., 83, 139(242) Marie, I., 410, 423(1026-28) Marino-Albernas, J. R., 111, 112. 141(294) Mariott, J. V. R., 278, 280,285, 331(149)

Marker, V. E., 411,423(1048) Markevich, I., 274,296, 330( 101) Marks, T. J., 275,286, 287, 288, 330(128) Markus, A., 73, 137(173) Marquardt, P., 273,330(98) Marra, A., 52, 136(118) Marsh, R. A., 400, 402,420(910) Martin, A., 36, 104, 135(79) Martin, J. B., 397, 419(882) Martin, R. G., 206, 208, 215, 259(35) Martin, R. P.,41, 76, 95, 97, 111, 115, 118, 120, 121, 123, 135(86, 87) Martineau, R. S., 217, 259(53) Martinez, R. V., 44,45,46, 48, 135(100) Martinez-Bernhardt, R., 44, 45, 46, 48, 135(100) Martin-Leon, N., 113, 114, 121, 123, 141(304) Martin-Lomas, M., 20, 21, 22, 26, 32, 33, 34, 35, 36, 51, 52, 55, 56, 65, 70, 76, 81, 83, 97, 98, 99, 102, 103, 117, 129, 134(36, 68), 136(114, 119, 142), 138(196), 139(246), 142(348) Martin-Zamora, E., 69, 83, 137(154) Marton, J., 413, 425(1100) Marton, T., 413,425(1100) Marusza, K., 325, 326, 342(611) Maruyama, J., 413, 425(1112) Maryanoff, B. E., 186, 198(114) Marzi, M., 112, 141(302) Mash, E. A., 44, 45,46, 47, 105, 135(101), 140(277) Mason, J. M., 19, 35, 70, 105, 137(158). 140(281, 282) Masunari, K., 117, 141(321) Masuyama, H., 374, 416(773) Masuyama, I., 388,418(854) Mateo, F. H., 73, 137(175) Matheson, N. K.. 296, 333(268) Matheu, M. I., 158, 159, 197(64) Matsuhira, N., 35, 36, 53, 54, 55, 75, 77, 84, 105, 114, 123, 135(77) Matsui, M.. 32, 33, 53, 64, 66, 68, 69, 101, 102, 103, 111, 126. 127, 134(67), 135(74, 7 3 , 140(263), 142(329, 330, 333) Matsui, Y.,75, 138(187) Matsumoto, M., 413, 425(1110) Matsuoka, N., 413,425(1103) Matta, K. L., 75, 80, 138(189), 139(226)

AUTHOR INDEX Matter, H., 126, 142(334) Mattes, M. J., 253, 261(104) Mattocks, A. M. N., 381, 383, 417(802) Matyko, M. A., 297, 334(307, 308) Maulshagen, A., 73, 137(167) Maurer, W., 311, 338(439) Mawle, A., 217, 259(54) Maxwel, J. L., 402, 420(923) Mayer, F., 219, 253, 259(56), 270, 296, 329(78), 386,418(834) Mayerhoefer, H., 277, 290, 291, 292, 293, 331(140) Mayhew, E., 111, 112, 141(294) Mazurkiewicz, J., 271, 272, 329(83, 84) McCarthy, T. J., 364, 376, 415(712) McCarty, M., 229, 232, 238, 239, 251, 259(69), 260(73) McCowage, R. J., 402, 420(917) McCready, R. M., 269, 274, 296, 329(73), 333(255), 334(277) McDonald, F. E., 127, 129, 142(345) McDonald, M. P., 318, 339(505) McFarlane, W., 19, 35, 133(25) McIver, H., 325, 341(596) McKenzie, S., 280, 332(183) McOskar, D. E., 397, 419(882) Medcalf, D. G., 296, 320, 333(271), 340(539) Mehltretter, C. L., 396, 419(872) Mehta, G., 188, 199(149) Mehta, S., 170, 173, 175, 197(80, 82) Meikle, P. J., 253, 260(101) Meinecke, C., 296, 332(230) Meinjohanns, E., 52,64, 136(123) Meinwald, E. C., 322, 340(551), 381, 384, 417(803) Meissner, J. W. G., 76, 138(192) Mellanby, J., 327, 342(645) Melnikova, L. V., 296, 333(244) Melvin, E. H., 301, 306, 309, 311, 312, 336(359), 337(425), 338(440) Menger, A., 397, 400,419(881), 420(897) Mentzer, M. J., 411, 424(1050) Mercer, G. A., 278, 284, 331(146) Mercier, C., 388, 391, 418(855) Merckel, J. H. C., 320, 321, 340(536, 537), 366, 367,416(743) Meredith, P., 387, 398, 418(843), 419(886) Mereyala, H., 41, 95, 106, 110, 118, 123, 135(85), 141(286)

445

Merienne, C., 85, 99, 115, 140(252) Merkel, H., 410,423(1034) Meuser, F., 369, 370, 390,393, 416(748), 418(857) Meuser, R., 370,390,392,416(749) Meyer, K. H., 266, 268, 274, 329(58), 363, 366,412,415(706, 722, 723), 424(1071) Meyerhoeffer, H., 290, 332(213) Mezhennyi, Ya. F., 360, 361,415(694) Mian, N. H., 296, 333(258) Michalska, M., 150, 152, 196(43-49.51) Michalski, J., 150, 152, 196(43,44,47) Mickey, C. D., 148, 149, 196(36, 37) Miezis, Y., 400, 420(896) Mikhailova, L. E., 297,335(313) Mikus, F. F., 278, 331(147), 369, 371, 416(752) Miles, M. J., 400, 402, 420(910) Miller, J. L., 325, 341(597) Miller, R. A., 80, 139(229) Miller, T. J., 85, 140(257) Milligan, T. P., 386, 418(822) Mills, S. J., 83, 139(241) Milovanovic, L., 319,340(525) Milstein, C., 202, 258(7) Minagawa, M., 366, 415(711) Minischi, F., 164, 165, 197(72) Minoru, T., 296,333(248) Minto, W. L., 266, 329(55) Mirescu, J., 264, 265, 328(29,33) Misiti, D., 112, 141(302) Miskiel, F. J., 202, 206, 209, 213, 214, 232, 233, 236, 237, 242, 243, 245, 246, 247, 255, 256, 258(6, 10, 16, 30), 259(37,49), 260(87, 90) Mitchell, J. F., 411, 423(1043) Mitchell, W. A,, 319, 339(519), 367, 390, 416(744),418( 856) Mitsubushi Electric Carp., 413, 426(1126) Mitsugi, K., 409, 422(1010) Mitsui, N., 413, 426(1133) Miwa, T., 186, 187, 198(125) Miyake, K., 413,426(1128) Miyake, S., 413, 426(1129) Miyazaki, H., 413, 425(1112) Miyazaki, T., 73, 80, 137(160) Miyazaki, Y., 272, 280, 330(93), 331(164, 168) Mizutani, J., 78, 138(206) Moffatt, J. G., 17, 86, 99, 100, 133(1)

446

AUTHOR INDEX

Mokhnach, V. O., 264,274,284,297, 328(11), 334(307-309). 335(312) Molines, H., 192, 199(153) Moller, U., 73, 137(173) Monahan, R. 111, 144, l86,195(3h), 198(114) Monden, R., 55,66, 136(141), 137(148) Monneret, C., 36, 104, 105, 107, 115, 135(79), 140(269,271), 141(312) Monte, R. W., 413, 425(1117) Montgomery, E. M., 361, 365, 415(704) Moore, R. E., 19, 113, 133(14) Moore, S., 367,415(728) Moore, T. E., 296,333(235) Mootoo, D. R., 170. 197(84,85) Morcuende, A., 19, 133(15-17) Moretti, P., 319,339(510) Morgans, D. J., Jr., 185, 198(109) Mori, Z., 399, 419(888) Moriguchi, I., 381,417(799) Moritaka, S., 367, 386, 416(741), 418(837) Moriya, K., 413,425(1113, 1114) Morozov, A. A., 411,424(1054) Morris, S. G., 314, 338(464) Morris, V. J., 400, 402, 420(910) Morrison, G. A., 373,416(768) Morrison, W. R., 386, 387, 396,418(822, 825,831, 838, 843). 419(877) Morsi, M. K. S., 308, 337(415) Morton, J. A,, 192, 199(153) Moschkoff, A., 299,335(337), 400,420(905) MBsinger, E. M., 54, 65, 136(136) Mossman, C. J., 44.48, 135(97) Mottadelli, S., 126, 142(335) Mould, D. L., 275, 278,296,297,330(122), 333(265) Moyano Olson, G., 287,293,332(210) Mozgovoy, A. A., 301, 335(349) Mu, P., 75, 138(186) Muchejee, A. K., 280, 331(163) Muetgeert, J., 298,323,335(326), 341(568) Muhn, R., 187, 199(141) Mukai, K., 319, 339(518) Mukaiyama, T., 44,45,46,48, 135(94, 96) Mukaiyama, Y., 186, 198(113) Mukherjee, A. K., 280, 331(167) Mukherjee, S., 274, 296, 330(105) Mukherji, K. C., 322, 326, 341(564) Mulard, L. A., 77, 138(199) Mullen, J. W., 412, 424(1069)

Muller, D., 73, 137(137, 167) Multon, J. L., 303, 336(377) Mundy, B. P., 186, 187, 198(131) Murakami, H., 275,277,286, 330(130), 332(207) Murakami, N., 84, 139(249) Murakami, R., 324,341(584-586,589,590) Murata, S., 187, 188, 199(146) Murayama, S., 74, 138(184) Murga, J., 112, 141(297) Murphy, M. J., 296,334(291) Murray, H. D., 274,330(103) Muschter, F. J. F., 318, 319,339(504, 509) Muscolino, G., 319, 339(510) Musso, H., 384,417(816) Muzimbaranda, C., 326,342(626) Myers, R. R., 292, 295, 332(214) Myrback, K., 274,279,330(104), 331(153) Myslinska, Z., 411,424(1049) Mysorekar, S. V., 44,46, 135(98, 99)

N Nfidvornik, K., 25,134(46) Naegeli, S., 272, 330(96) Naegli, C., 324, 341(581), 376,417(781) Naganawa, H., 87, 100, 140(260) Nagashima, N., 32,33, 34,42, 43, 44, 45,48, 111, 112, 131, 132, 134(65, 69) Nahorski, S. R., 102, 103, 140(265) Nakabayashi, S., 70, 116, 126, 127, 137(156), 142(328,331, 332) Nakahara, Y., 366,415(711) Nakai, T., 413,426(1129) Nakaji, T., 55, 136(138) Nakamura, A., 387,418(844) Nakamura, M., 413, 426(1133) Nakamura, S., 408,409, 422(1001, 1011) Nakamura, Y., 274,330(116) Nakano, T., 66,69,71, 126, 137(150) Namazi, H., 61, 62, 81, 96, 98, 136(145b, 145c), 139(231) Nandan, S. R., 114, 141(306) Nanji, H. R., 268, 329(59) Nara, S., 280, 299,306, 308, 312, 331(176), 335(329, 330), 337(407) Nashed, M. A., 32,36, 72,73, 74,77, 82, 117, 134(66), 137(159, 168-170). 138(181. 184,201), 141(320) Nath, H. P., 296, 333(259)

AUTHOR INDEX Nath, N., 296, 333(259) National Starch and Chemical Corp., 413, 42S(1121) Navia, J. L., 77, 138(200) Nawata, Y., 327, 343(646) Nazarov, V. I., 264,280,327(2), 331(179), 381, 417(800) Nebesny, E., 374,416(769) Nedelceva. M., 413,425(1101) Neidle, S., 155, 156, 188, 196(61), 199(150) Nekryach, E. F., 360, 361,415(694) Nekryach, J. F., 309, 337(433) Nelson. G. E., 325, 341(598) Nelson, J. M., 367, 416(742) Nematalla, A. S., 72, 137(159) Nembert, A. M., 296, 333(249) Nemitz, G., 298, 311, 335(324) Nesmeyanov, A. N., 411.423(1041) Neumann, K., 18, 78, 82, 98, 133(9) Neville, A., 209, 226, 258(45) Newell. J., 405,421(974) Newzer, I. I., 326, 342(618) Nicolaou, K. C., 73.80, 137(160),139(229), 144, 184, 185, 186, 191. 195(4), 198(102, 103. 118) Nicoli, L., 400,403, 420(908) Nicotra, F.. 52, 136(121) Niedzielski, 2.. 400, 420(903) Nielsen, E., 296. 334(286) Nieto-Sampedro, M., 76, 138(196) Nikolaev, B. A,. 409, 422(1005, 1006, 1008) Nikolaev, L. A,. 265, 328(37) Nikulina, L. A., 297, 335(319) Nikuni, Z., 296, 333(270), 410,423(1023) Nilsson, M., 52, 106, 136(117) Nilsson, S., 174, 197(89) Nilsson, U., 75, 76, 138(190) Nimkar, S. K., 105, 140(277) Nishide, E., 413. 425(1106) Nishimura, M., 49, 53, 54, 64, 65, 84, 105, 106, 114, 135(106) Nishimura, %I., 74, 138(184) Nishimura, Y., 184, 198(99) Nishiyama, S., 87, 140(261) Nishizawa, M., 184, 191, 198(104) Nitta, Y., 316. 339(483) Nixon, A. C., 412,424(1062) Nogier, T., 293, 332(220) Noltenmeyer, M., 276, 277, 286, 330(132, 133)

447

Nomenclature of Carbohydrates, 18, 133(8) Nomoto, T., 185, 198(107) Nomura, Y.,186, 187, 198(127) Norberg, T., 174,197(89) Norman, L. W., 400,420(902) Nortey, S . O., 186, 198(114) Nosov, M. P., 303, 336(378), 359, 374 Nossian, W., 300, 335(345) Nottbohm, F. E., 386,418(834) Novais, J. M., 409,410,422(1013) Novak, B., 319,339(511) Novak, V., 296,333(239) Nowotny-Rozanska, M., 272,329(84) Noyori, R., 185,198(111, 112) Nozaki, H., 126, 142(336) Nudelman, A., 126,127, 142(339, 340,342) Nuhn, P., 145, 146, 148,195(16-20). 196(22-23,25, 26) Nukada, T., 101, 103,116, 140(263), 141(317) Nurkas, M. M., 324, 341(578) Nutting, G. C., 402,403, 420(929) N.V.W.A. Scholten’s Chemische Fabnken, 399, 419(891, 892) 0 Oba, K., 367, 369,416(740) Obe, K., 117, 141(321) Obroniecka, L., 413,425(1108) Oda, T., 388,418(854) Ofelt, C. W., 396, 419(871, 872) Ogawa, K., 271,329(80) Ogawa, S., 44, 45,56, 114, 135(74,75, 95, 108), 136(144), 141(307) Ogawa, T., 32, 33, 49, 53, 64,66, 68, 69, 70, 71, 76, 97, 101, 102, 103, 111, 112, 116, 126, 127, 134(67), 137(150, 156), 138(194), 140(263), 141(296,317), 142(328-333 ), 186,187,198(138) Ogino, H., 349, 352, 366,414(661), 415(723a) Ogrodnik, S . T., 411, 424(1054) Oh, K. S., 63, 137(147) Ohara, E., 186, 187,198(126) Ohara, M., 367,416(735) Ohashi, K., 297, 334(300), 396,419(876) Ohno, M., 32, 33, 34,42, 43, 44, 45,48, 111, 112, 131, 132. 134(65, 69) Ohta, K., 117, 141(321), 367,416(735)

448

AUTHOR INDEX

Oiji Cornstarch Co., Ltd., 413, 425(1115), 426(1127) Ojima, T., 411,423(1038) Okada, K., 299. 312, 335(329) Okamoto, K., 407,422(992) Okawara, R., 25,29, 134(55) Okaya, T., 413,425(1113, 1114) Okazaki, N., 271,329(80) Okumura, K., 374, 375,417(775) Okuno, Y., 35, 36, 53, 54, 55, 75, 77, 84, 105, 114, 123, 135(77) Oleinikova, A. Ya., 400, 420(906) Olesker, A., 124, 125, 142(325) Olesyuk, A. D., 326,342(615) Olifson, L. E., 297, 335(313) O h , D. E., 234,260(75) Olson, S. H., 79, 106, 118, 138(210) Olsson, L., 79, 138(215) Onami, T., 265,328(36) Ono, M., 384, 417(815) Ono, S., 271, 272, 213, 275, 280, 281, 284, 303, 306,311, 329(80, 91, 92), 332(184, 189), 336(369), 337(403,404) Opie, W. J., 413, 426(1137) Oriyama, T., 127, 129, 142(345) Orlich-Krezel, I., 150, 196(43, 44) Ors, M., 19, 133(17) O’Rurke, J. D., 319,339(519), 390,419(856) Osborne, D., 411,424(1052) Oscarson, S., 44, 79, 129, 130, 135(92), 138(215), 142(349) O’Shea, G. K., 322, 323,341(566) Oshitari, T., 79, 139(216, 217) Oshiuni, R., 366,415(711) Osman, E. M., 388, 396, 402, 403,418(850), 419(868), 420(92 1), 421(935) Osman-Ismail, F., 348, 353, 354, 355, 359, 363, 365, 366, 367, 373,414(656, 658, 680) Ostrowska, S., 400, 420(894, 895) Ostwald, W., 408,422(995) Otani, Y., 296, 333(256), 334(280) Otey, F. H., 324, 341(587), 396,419(872) Ott, A. Y., 72, 96, 137(162) Ouchterlony, O., 205,258(27) Ourisson, G.. 364,415(713) Owens, H. S., 269,274, 296, 329(73) Owens, M. S., 296, 333(255) Oxford Paper Co., 326, 342(614)

P Packer, K. J., 25, 29, 134(56) Paik, S., 19, 113, 133(14) Pars, M., 36, 104, 135(79) Pal, M. K., 266, 293, 329(56), 332(225), 384. 418(819) Pal, P. K., 266, 329(56), 384 Palasinski, M., 316, 339(486, 487). 351, 357, 360, 386, 414(677, 689) Palenik, K., 411,424(1049) Palka, A., 311, 312, 338(443) Paloheimo, L., 296, 333(246) Pan, J. W., 85, 106, 140(251), 141(288) Panchenko, M. S., 301,336(360) Pancu, M., 413, 425(1104) Panza. L., 52,136(121) Panzer, W., 403, 421(932) Park, J. T., 209, 259(41) Park, T. K., 74,101, 106, 138(182), 141(292) Parker, R., 302,336(364) Parton, A. P., 80, 139(229) Partridge, S. M., 219, 259(58) Pascal, P., 264, 328(10) Pascard, C., 29, 30, 134(59) Paschall, E. E., 284, 332(202) Paschall, E. J., 284,332(203) Pascu, E., 412,424(1069) Pasternack, A., 400, 420(900) Patai, S., 144, 195(3i) Patel, R. B., 322, 340(557) Patil, N. B., 412, 424(1072) Paukstelis, J. V., 403, 421(949, 950, 951) Paulsen, H., 52, 64, 65, 85, 99, 136(122, 123), 140(255, 262), 167,182, 197(76), 198(98) Pavlovic, D., 316, 339(479) Pawar, S. M., 44, 135(99) Payen, A., 272,293,298,330(95), 332(218) Payne, S., 83, 139(238, 239) Pazur, B. A,, 232,236,237,239,240, 258(6), 260(79) Pazur, J. H., 202, 204,206,208, 209,210, 211,213,214,215, 218, 219, 222, 223, 224, 225, 226, 229, 230, 231, 232,233, 236, 237, 239, 240, 242, 243,245, 246, 247, 249, 250, 251,252, 253, 254, 255, 256. 258(3, 5 , 6, 10, 15-17, 19, 20, 26. 30), 259(32-34, 36-38,47-49, 57, 60, 62-65), 260(72, 79, 81-83, 87-91, 95-98), 261(109)

AUTHOR INDEX

Pearce, M., 51, 75, 77, 136(113) Peat, S., 274, 280, 296, 316, 330(114), 331(165), 334(281), 339(482) Peck, G . E., 303, 336(381) Pedretti, C., 118, 141(323) Pedretti, V., 55, 136(137) Pelletier, M., 405, 421(962) Peltser, A,, 313, 338(452) Penades, S., 83, 102, 139(246) Penczuk, A. G., 413, 426(1132) Peng, Q. J., 271. 288,289,290,329(81) Pennings, H. J., 396, 397, 419(880) Pennings, N. J., 133, 142(354) Pennsalt Chemicals, 322, 326, 341(562) Pereyre, M., 17, 133(4) Perez, M., 157, 197(62) PerCz, S., 266, 329(51, 52) Perisic-Janjic, N., 319, 340(523, 524), 367, 373, 415(727), 416(758) Perlin, A. S., 271, 288, 289, 290, 329(81) Permin, A. B., 20, 133(26) Perry, M. B., 253, 260(101) Personius, C. J., 402, 403, 420(922) Personne, J., 293, 332(219) Persoz, J., 272, 298, 330(95) Petasis, N. A,, 144, 184, 185, 191, 195(4), 198(103) Peters, A,, 111, 112, 141(294) Peters, T., 253, 260(101) Peterson, J. M., 106, 127, 129, 141(292), 142(345) Peterson, K., 253, 260(100) Petho, M., 322, 323, 341(565) Peticolas, W. L., 282, 283, 288, 332(197) Petitou, G., 73, 137(163) Petrosyan, V. S., 19, 20, 133(22, 26) Petrova, A. N., 410,423(1020-1022) Petrovic, J., 367, 416(733) Petrovic. S. E., 367, 416(732) Petrovic, S. M., 367, 416(732) Petrus, L.. 131, 132, 142(352) Petrzilka, M., 154, 196(55, 56) Pettitt, D. J., 245, 260(86) Pfannemtiller. B., 276, 279, 285, 286, 287, 290, 330(136), 331(152), 332(213) Pfeiffer, G . , 324, 341(577) Pfleger, R., 373,416(765) Pharmacia, 203, 204, 258(23) Phillips, A. T., 269, 290, 329(72) Phillips, G . O., 245, 260(86)

449

Pierce, F. T., 305,337(400) Pilnik, W., 409,410,423(1015) Pinel, C., 19, 44,46, 49, 51, 111, 115, 116, 121, 122, 133(12, 13) Pinnow, J., 296, 333(231) Pinto, B. M., 170, 173, 175, 197(80, 82) Pischel, H., 145, 195(16) Pitteloup, R., 154, 196(56) Pittsley, J. E., 209, 258(44) Plaza Lopez-Espinosa, M. T., 84, 98, 139(247) Pliska, V., 367,415(725) Ploetz, T., 274, 330(107) Pock, G . E., 305, 337(402) Podder, S. K., 281, 332(188) Poersch, W., 304, 336(391) Pohl, J. J., 293, 332(216) Polewski, K., 384, 418(818) Poliszko, S.,301,336(361), 361,414(691) Pollak, 0. J., 364,415(714) Polymer Corp. Ltd., 326, 342(612) Pomeranz, Y.,386,418(823) Ponnampalam, R., 131, 132, 142(351) Ponomarev, V. D., 325, 342(607) Pontikis, R., 115, 141(312) Poole, W. K., 305, 337(396) Popov, I. D., 317, 320, 339(498), 340(534) Popova, E. R., 297,335(312,315,316,318) Popova, N. M., 322, 340(552) Porath, J., 202, 204,258(13) Portal, M., 112, 141(299) Portowkalian, J., 253, 261(103) Potter, A. L., 269, 274, 296, 329(73) Potter, B. V. L., 42, 49, 50, 63, 68, 69, 82, 83, 102,103, 135(91), 137(152), 139(235, 241), 140(265) Potter, M., 239, 260(78, 80) Pougny, J. R., 184,198(101) Power, W. P., 24, 27,30, 134(39) Powis, G., 83, 139(240, 245) Pozsgay, V., 73, 137(164) Prandi, J., 73, 104, 106, 110, 137(178), 141(287, 290) Prestwich, G . D., 83, 139(242) Pretorius, J. A., 25, 27, 28, 30, 97, 134(51) Prezzhaeva, L. G., 406,422(982) Price, A. J., 25, 27, 30, 32, 134(52, 62) Price, J., 144, 195(2) Priebe, W., 159, 197(65) Prodger, J. C., 77, 138(198)

AUTHOR INDEX

450

Propp, L. N., 297, 334(309) Provdanov, C. E., 409,423(1017) Przylecki, S. J., 323, 341(567), 349, 408, 414(666), 422(997) Pulatov, T., 297, 334(310) Pulley, A. O., 280,332(181), 348, 351, 355, 363,414(657) Purves, C. B., 303, 336(380) Puskar, Y. K., 20, 133(26) Putilova, 1. N., 326, 342(616) Putscher, J. J., 411,424(1051) Pybus, J. N., 317,339(492) Pyda, M., 361,414(691) Pyslarach, S. S., 297, 334(311)

Q Qin, H., 49, 50, 51, 54, 61, 62, 63, 66, 68, 69, 70, 101, 103, 135(110), 137(151) Quintard, J. P., 17, 133(4)

R Rabelo, J. J., 148, 149, 196(29-33) Rabold, C. N., 384,418(817) Rachinskii, V. V., 313, 338(452) Radley, J. A., 365,415(705, 720) Radosavljevis, S., 319, 340(523) Rahm, A., 17,133(4) Rahman, K. M. M., 105, 107, 140(270) Rahrnatalla, M. T., 298, 335(322) Raja Reddy, K., 188, 199(149) Rakhimov, K. K., 297,334(310) Rakovskii, A. V., 313,314,315, 316, 338(462,467), 339(481) Rakowski, A., 299,300,308,314,315, 335(327,331-333), 338(466,468,477) Ralph, J., 54, 55, 67, 68, 69, 70, 105, 106, 131, 136(132) Rama, N., 325, 342(608) Rana, S. S., 80,139(226) Randall, R. J., 232, 238, 239, 251, 260(74) Randolph, J. T., 74, 101, 106, 116, 138(182), 141(319) Randdamandimby, D., 162, 163, 165, 166, 167, 177, 197(68,71,78,95) Rao, A. V. R., 44,135(98) Rao, C. V., 409, 423(1018) Rao, H. S. P., 188, 199(149)

Raphael, R. A,, 186, 187, 198(123) Rappenecker, G., 304,336(384) Rappoport, Z., 144, 195(3i) Raschke, W. C., 255,261(105) Rasper, V. F., 402, 420(912) Rassow, B., 378,417(792) Rateb, L., 117, 141(320) Rathgeb, P., 363,415(706) Ray, A. K., 75, 76, 138(190) Raymond, A. L., 143, 195(1) Razumikhina, N. S., 327,342(640) Read, R. W.,186, 187, 198(129) Reams, P., 25, 29, 134(56) Rebar, V., 308, 337(417), 360 Rebentisch, M., 313, 338(457) Reck, F., 52,64, 65, 136(122, 123) Recke, R., 404,421(957) Reddy, K. C., 46,135(103) Reddy, K. K., 83, 139(243) Reddy, K. R., 78, 138(204) Reed, A. J., 226,256,259(65), 261(109) Reese, C. B., 155, 156, 188, 196(61), 199(150) Reginato, G., 40, 111, 115, 123, 135(84) Rehfeld, C. G., 410,423(1037) Reichard, P., 405,421(973) Reichel, M., 274, 330( 115) Reichert, E. T., 376,377,417(787) Reilhes, R., 272, 329(90) Reitz, A. B., 114, 123, 141(308), 186, 198(114) Rendleman, J. A., 322, 325, 340(549) Reschko, C., 373,416(767) Reychler, A., 315, 317,338(469), 339(501-503), 373,416(760) Rezler, R., 301, 336(361) Ricci, A., 40, 111, 115, 123, 135(84), 142(324) Richards, J. C., 80, 139(227) Richardson, S. J., 403, 421(940-942) Richter, M., 268, 281, 296,297, 329(68), 332(187), 333(251), 334(297) Richter, P. K., 80, 139(229) Riley, E. F., 359, 414(688) Ring, S. G., 409,410, 423(1016) Rio, S., 106, 140(284) Rion, P., 313, 338(453) Ripoche, M. J., 306, 337(406) Rist, C. E., 296, 334(278) Ritchie, T. J., 186, 187, 199(140)

451

AUTHOR INDEX Rivat, G . , 296, 333(232) Rizzuto, A. B.. 400,420(907) Robarge, K. D., 186, 187, 188, 198(120, 121) Roberts, H. J., 365. 415(721) Roberts, J., 412, 424(1081) Robertson, J. S. H., 296, 333(260) Robinson, A,, 145, 195(14) Robinson, J. L., 400, 401, 420(898, 899) Robinson, R. J., 392, 419(858) Robles-Diaz, R., 163, 166, 197(70, 73) Robyt, J. F., 357. 360,414(685) Rochet, P., 46, 135(102) Rodewald, H., 309, 337(429,430) Rodriguez, S., 112, 115, 122, 141(297,313) Rodriguez-Amaya, D. B., 396, 400,402, 419(878), 420(909) Roe, J. H., 296, 334(290) Roelens, S., 25, 30, 40, 41, 98, 100, 111, 115, 123, 131, 134(50, 53, 61), 135(83, 84), 142(324) Rogols, S., 296, 334(287) Rogozhin, C. V., 411, 423(1041) Rohmer. M., 364,415(713) Rokia-Trygubowicz, T., 152, 196(51) Rollin, P., 184, 198(110) Romanic, B. M., 239, 260(82) Romanov, L. G., 325, 342(607) Romanowska, E., 253, 260(100) Romaszeder, K., 324, 341(583) Rombouts, F. M., 73, 137(176) Roncato, A,, 265,328(31) Roozen, J. R., 409, 410,423(1015) Roscher, N. M., 10 Rosebourne, C., 322,340(550) Rosebrough, N. J., 232, 238,239, 251, 260(74) Rosen, S. D., 75, 77, 138(185) Rosenthal, F. R. T., 296,333(272) Rossotti, H., 277, 286, 313, 331(139), 332(206) Roth, Z., 127, 142(342) Rouger, J., 412, 424(1079) Rousseau, E., 293, 332(222) Roversi, G., 304, 307. 336(389) Rovnak, S. E., 239, 240, 260(79) Roy, A,, 293, 332(225), 384,418(819) Roy, N., 77, 138(197) Roy, R.. 105, 140(276) Ruby, S. L., 275, 286, 287, 288, 330(128)

Rudenko, E. L., 297,334(311) Ruegge, D., 154,196(54) Ruess, K.-P., 112, 141(295) Rundle, R. E., 264,265, 266, 268, 269, 270, 274,275, 276,277,278, 284,290,294, 303, 328(4, 5, 18), 329(48, 49, 65), 330(106, 110, 111, 123, 124, 129), 331(147), 346, 347,369, 371,414(653), 416(752) Rusakova, N. M., 264,274, 284,328(11) Russell, C. R., 327, 343(648, 649) Russo, G., 52, 136(121) Rutgers, R.,366, 415(724) Rutschmann, M. A., 297,334(296), 365, 366, 367,393,395,415(717,725) Rybalko, N. L., 410,423(1031) Rychlewska, M., 327, 342(638) Rysev, A. P., 281, 332(193) Ryu, Y.,52, 63, 136(129), 137(146, 147) S

Saenger, W., 264, 276, 277,286,303, 328(13), 330(132, 133). 336(383) Saez, V., 77, 138(198) Safronov, A. P., 327,342(640) Saha, U. K., 79, 82, 98,127,138(212), 139(233), 142(341) Sahai, M., 127, 142(342) Sair, L., 308, 309, 337(420) Saito, S., 319, 339(517), 375, 376, 417(776) Saito, Y.,105, 140(283) Sakai, H., 402,420(928) Sakai, M., 296,333(270) Sakakibara, K., 412,424(1063) Sakakibara, T., 186, 187, 198(126, 127) Sakamoto, M., 87, 100,140(260) Sakano, K., 366,415(711) Sakoda, M., 87,140(261) Salter, J. H., 376, 417(786) Salton, M. R. J., 209, 259(40) Saluvere. T. A., 20, 133(26) Samarina, I. A., 409, 422(1006) Samec, M.,268, 269,270,296, 300,329(63, 66,77, 78), 334(285), 335(339), 412, 424(1068), 425(1091) Samuel, A. G., 41, 95,118,123,135(85) Samuel, J. O., 317, 321, 339(496), 340(547) Samuel, W. A,, 326,342(622) Samuelson, B., 179, 197(97)

452

AUTHOR INDEX

Sand. D. M., 313, 338(450), 350, 373, 414(669) Sandford, P. A., 10 Sandstedt, R. M., 405, 421(967) Sano, T., 281,332(191), 375,417(777) Sansstedt, R. M., 409, 422(1012) Santoyo-Gonzalez, F., 163, 164, 166, 197(70, 73) Sapronov, A. R., 410,423(1031) Sargent, J. G., 405,422(978) Sarkar, A. K., 106, 141(285) Sasajima, K., 70, 116, 126, 127, 137(156) Sasaki, I., 409,422(1011) Sasjima, K., 126, 127, 142(330, 332) Sato, K . 4 , 101, 104, 140(264, 275) Sato, T.. 126, 142(336), 185, 198(111, 112), 316,325,339(480), 341(603), 413, 425(1113, 1114) Sato, Y., 35, 36, 49, 50, 51, 53, 54, 56, 57, 64, 65, 81, 84, 105, 106, 114, 115, 123, 135(78, 106) Saule, S., 281, 332(194) Savage, H. L., 403,421(935) Savina, I. M., 306, 337(408) Sawa, T., 87, 100, 140(260) Sawyer, D. A., 82, 139(235) Sazhin, B. S., 301, 336(360) Scapecchi, S., 40, 1 11, 115, 123, 135(84) Scatchard, G., 348,414(660) Schaaf, E., 274,330(107) Schachter, H., 52, 64, 136(123) Scharf, H.-D., 104,140(273) Scharff, M. D., 202, 258(8) Schering, R., 266, 329(54) Schierbaum, F., 299. 300,301, 309,310, 311, 335(328, 347, 348), 336(356-358), 337(426), 338(438,446), 348, 351, 353, 354,357,359,363,364,365,366, 367, 371, 373. 411,414(659. 681,682), 416(766), 423(1044) Schilling, C. H., 263, 345 Schink, N. E., 412, 424(1075) Schinner, A., 266, 329(57) Schlamowitz. M., 276, 277, 330(135) Schlenk, H., 313, 338(450) Schlenk, M., 350, 373,414(669) Schlewer, G., 52,63, 83, 136(127), 139(244) Schmalfuss, H., 404, 421(957) Schmidt, R. R., 116, 126,141(315), 142(337, 338)

Schmiesing, R. J., 154, 166,196(58,59) Schmitt, L., 52, 63, 136(127) Schmitz, H., 386,418(856) Schneider, F. W., 281, 332(190) Schneider, W., 144, 145, 195(7, I l ) , 281, 332(188) Schnetz-Boutand, N., 83, 139(244) Schnute, W. C., 229,260(71) Schoch, T. J., 310, 315, 322, 324, 325, 338(437), 340(551), 361, 363, 368, 369, 371, 376, 381, 384, 396,415(699, 705), 416(747,750,751), 417(803), 419(874) Schoenbein, C. F., 293, 332(215) Schofield, J. D., 405, 422(978) Schoh, T. J., 270, 280, 296, 329(79), 331(182) Scholz, P., 318, 339(508) Schoppe, H., 404,421(957) Schreiber, H., 249, 260(93) Schreiner, E. P., 73, 80, 137(160) Schrenk, W. G., 309, 337(432) Schuerch, C., 73, 80, 81. 124, 125, 137(171), 139(223, 224) Schiile, G., 79, 139(220) Schiiller, A. M., 85, 140(250) Schultz, R., 296, 333(253) Schulz, A. P., 378,381,417(793) Schulz. R. C., 277, 290, 291, 292, 293, 331(140), 332(213) Schulze, T. J., 73, 80, 137(160) Schumann, W., 327,343(646, 647) Schwaneberg, U., 79, 139(220) Schwartz, M. E.. 86, 100, 140(256) Schwiabold, S., 319, 339(521) Schwier, J., 302,336(365) Schwimmer, S., 349, 414(664) Scoggins, W. C., 302, 336(365) Scott, R., 407,422(986) Scrano, R. E., 226, 259(65) Sebald, A., 25, 29, 134(56) Seed, J. R., 308, 337(416) Seibel, W., 397,419(881) Seiberlich, J., 317, 339(493) Seibert, F. B., 367, 416(730) Seidel, W. C., 319, 339(519), 390,418(856) Seidemann, J., 317, 339(490), 378, 382, 417(795) Seigner, C., 409, 423(1017) Sekar, K. C., 405,421(964) Semkina, L. I., 412, 425(1099)

AUTHOR INDEX

Semple. J. E.. 153, 196(52) Sen, K. C., 264, 328(6) Sengupta, K. K., 280,331(167) Senti, F. R., 209, 258(44), 396,419(871, 872) Serianni, A. S., 133, 142(354) Serling, J., 126, 142(339) Sethi, R. K., 311, 338(445) Setser, C. S., 403,421(949-951) Settele, W., 325, 341(600) Severn, W. B., 80, 139(227) Severson, G. M., 361, 369, 412,415(701, 702). 424(1076) Sexson, K. R., 361, 365, 415(704) Shanzer, A,, 44, 45, 135(93) Sharp, R. R.. 20,133(27,28) Shasha, B. S., 324, 341(587) Shaw, T. M., 302. 336(362) Shchegoleva, A. I.. 304, 337(395) Shcherban, Z. P., 321, 340(548) Sheldrick, G. M., 25, 134(54) Shellenberger, J. A., 307, 337(412) Shen, T. Y., 178, 197(96) Sheringa, K., 322.340(555) Shibata, K., 54, 66, 136(133) Shibata, Y., 44, 45, 135(95) Shiels, H. R., 209, 214, 258(37) Shikata, M., 303, 336(367) Shimada, K., 408, 422(999-1001) Shimamoto, T., 399,419(889) Shimizu, H., 76, 97, 138(194) Shimizu, M., 44, 45, 46, 48, 135(94,96) Shimizu, R., 387,418(844) Shimizu, T., 321, 340(541) Shimomura, T., 274, 330(116) Shimono. K., 413, 425(1103) Shin, J. E. N., 80, 139(225) Shin, Y.. 80, 139(225) Shinmitsu, K., 55, 136(138) Shira, K., 320. 326, 340(540) Shirota, T., 384, 417(813) Shkadina. S. S., 409, 422(1005) Shlyrkova, E. A,, 411, 423(1048) Shneerson, V. B., 326, 342(615) Shtyrkova, E. A,, 319, 340(531) Shulman. M. S., 309, 337(434) Sieling, F. W., 412, 425(1097) Siemsen, L., 73, 137(175) Sievert, D.. 393, 400, 419(861b) Signaigo, F. K., 326, 342(625)

453

Sikora, M., 352, 414(678) Silano, M. A., 413,426(1124) Silviera, V., 269,274, 296, 329(73), 333(255) Silwanis, B. A., 72, 137(159) Simerl, L. E., 270, 296, 329(76) Simmonds, D. H., 405, 422(977) Simons, I. W., 308, 337(416) Simpson, D. L., 245, 246, 260(88) Simpson, T. D., 275, 330(120) Sinag, P., 52, 55, 72, 96, 104, 107, 108, 118, 136(118, 137), 137(161), 140(267), 141(323), 154, 156, 184, 186,187, 192, 196(60), 198(100, 101, 124). 199(155-157) Singh, K., 76, 138(196) Singh, S., 296, 333(259) Sirota, J., 413, 426(1132) Sirotkin, V. V., 406,422(982) Skelton, B. W., 74, 137(179) Skrydstrup, T., 188, 199(151) Slater, S. D., 24,27, 29, 30, 134(40) Sliedregt, L. A. J. M., 173, 174, 177, 197(87) Slife, C. W., 74, 138(181) Slonimskii, G. L., 407,408, 411,422(987. 989). 423( 1041) Smart, J. S., 41, 76, 95, 97, 111, 115, 118, 120, 121, 123, 135(86, 87) Smid, P., 73, 137(176) Smith, A. L., 73, 80, 137(160) Smith, B. W., 296, 334(290) Smith, D. F.. 255, 261(108) Smith, F. A,, 373, 416(763, 764) Smith, F. R., 298, 299, 335(320) Smith, G. T., 271,329(82) Smith, J., 411, 423(1043) Smith, L., 20, 26, 134(34) Smith, L. T., 314, 338(464) Smith, P. J., 17, 19, 20, 21, 24, 25, 26. 33, 34, 35, 133(5, 23), 134(34, 35) Smith, R. L., 277, 331(144) Smith, W. T., 271, 329(82) Smits, S. A. W., 79, 106, 110, 139(219) Smolina, L. D., 308, 320,337(422), 340(533) Smykova, N. A., 323,341(569) Snatzke, G., 73, 137(167), 152, 196(49, 50) Sobczynska, D., 403,421(950) Sochor, C., 410, 423(1025) Solms, F., 348,414(658)

454

AUTHOR INDEX

Solms, J., 297, 334(296), 348, 353, 354, 355, 359,363, 365, 366, 367, 373, 393, 395, 400,401,414(656,679, 680). 415(717, 725), 420(898, 899) Solomina, L. S., 319, 340(531) Solomon, M., 186, 187, 198(139) Somasundaran, P., 319.339(520) Sordillo, J. D., 413, 425(1117) Sorgi, K. L., 154, 166, 196(58, 59) Sorokin, G. A,, 312, 313. 338(447) Soto Figueroa, E., 367, 416(730) Spanier, A. M., 253,260(102) Spies, R. D., 404,421(952) Spiess, B., 52, 63, 83, 136(127), 139(244) Spijker, N. M., 73, 137(163) Spohr, U., 73, 137(177) Spradlin, J., 409,423(1018) Springer, M., 52, 64, 136(123) Srivastava, V. K., 80, 81, 124, 125, 139(224) Sroczynski, A., 374, 416(769) Ssakun, N. J.. 299, 335(336) Stacey, M., 296, 334(281) Stahl, W., 73, 80, 137(160) Stamm, A. J., 309, 337(424) Starunskaya, T. P., 303,336(378), 359, 374 Staunton, J., 115, 141(310) Steffan, W., 72, 96, 137(162) Stein, R. S., 275, 276, 277, 303, 328(5) Stein, W.H., 367. 415(728) Steinberg, M. P., 403, 421(936, 937, 940-942, 944) Steinhoff, G., 378,381, 417(793) Stejskal, J. F., 412, 424(1064) Stender, J., 369, 370, 390, 392, 393, 416(748, 749), 418(857) Stengle, T. R., 403, 421(943) Stengle, T. S., 403, 421(945) Stenman, U. H., 400,420(900) Stepanenko, B. N., 323, 341(569) Stephan, H., 397, 419(881) Stephenson, E. E., 412,413,424(1083) Sterling, C., 308, 337(415,416) Sterling, J., 127, 142(340) Stem, E., 319, 324, 339(522), 341(582) Stevens, D. G., 412, 424(1064) Stewart, N. L.. 405, 421(976) Stibbard, I. H. A., 186, 187, 198(123) Stick, R. V., 74, 137(179) Stofko, J., 404, 421(959) Storgors, T., 367,416(731) Stork, G., 192, 199(154)

Stowell, C. P., 221, 259(61) Strandine, E. J., 396, 398, 419(869) Stranding, D. N., 167, 197(75) Strashchenko, E. S., 411,423(1044) Stromeyer. F., 264, 328(17) Struminskii. C. V., 407,422(987) Stylianides, N. A., 73, 80, 137(160) SU,T.-L., 124, 125, 142(326) Suda, Y.,384,417(813) Sudo, Y., 384,417(815) Sudoh, R., 186, 187, 198(126, 127) Sugiyama Industrial Chemical Institute, 367,416(745) Suida, W.. 376, 379,417(789. 790) Sukan, G., 323, 341(573) Sukhorukova, T. I., 381, 417(800) Sunblad, G., 249, 260(94) Sunner, E. D., 305, 337(396) Sustmann, R., 154, 187, 188, 196(54), 199(143) Sutherland, J. K., 106, 141(293) Sutra, R., 274, 330(102) Sutton, H. E., 384, 417(811) Suzuki, H., 263, 280, 327(1), 331(175), 348, 349, 352, 363, 366, 414(655, 661), 415(710, 723a) Suzuki, K., 186,198(113), 374,416(773) Suzuki. S., 326, 327, 342(630, 644) Suzuki, T., 73, 80, 137(160), 187, 188, 199(146) Svahn, C.-M., 52, 106, 136(117) Svensson, S., 52,56,82, 83, 136(128), 249, 260(94) Swan, E., 304,308,336(387,388), 337(414) Swanepoel, A. D., 131,132, 142(350) Swanson, C. L., 327, 343(648) Swanson, M. A., 277, 278, 284, 331(145) Synge, R. L. M., 296, 333(265) Synowiecki, Z., 327, 342(636) Szabb, L., 85, 99, 115, 121, 140(252, 253), 141(311) Szabo, P., 116, 122, 141(316) Szechenyi, L., 296, 333(250) Szejtli, J., 264, 269, 274, 275, 276, 277, 279, 280, 281, 282,283, 292, 293, 295, 296, 297,303, 319, 322, 323, 328(15), 329(70), 330(112, 119). 331(157-160, 166, 170), 332(186, 187, 196, 198), 333(263), 334(294,295,297,299), 336(382), 339(515), 341(565). 363, 371, 372,386,415(709), 416(753)

AUTHOR INDEX Szilagyi, L., 85. 99, 115, 140(253) Szmant, H. H., 49, 53, 135(105) Sznaidman, M., 159, 197(65)

T Taddei. M.. 25, 30, 134(50) Taeufel, K., 300, 301, 309, 310, 335(347), 336(357, 358). 337(426), 373,403, 416(766), 421(931, 932) Taft, R.. 313, 320, 338(458) Taguchi, N.. 263, 327( 1). 348, 352, 414(655) Takahashi, K., 273,281,294, 320, 326, 330(99), 332(189), 340(540), 364,413, 415(716), 426(1138) Takahashi, S., 296, 333(256) Takahashi, Y., 33, 69, 135(75) Takai, J., 186. 187, 198(126) Takai, Y., 101, 140(264) Takaku, H., 185, 198(107) Takano, K., 413, 425(1113, 1114) Takaoka, K., 296, 334(288, 289) Takatsuji, M., 413, 426(1129) Takeo, K., 54, 55, 66, 70, 73, 78, 81, 98, 136(133, 138), 137(157, 174), 138(205), 347,350,351, 353,354,355,357,359, 360. 363, 365, 366, 367, 371, 373, 409, 414(654, 673). 415(726), 416(754), 422( 1011) Takeoka, J., 114, 141(307) Takeuchi, I., 408, 422(999-1002) Takeuchi, T., 87,100, 140(260) Takeyama, H., 383, 417(806) Talib, Y. Y., 412,424(1066) Tamura, Z., 296, 333(270) Tanabe. Y.. 44, 46, 135(96) Tanaka, H., 184, 198(106) Tanaka, J., 275, 330(121) Tanaka, K., 409,422(1010) Tani, S., 372, 416(757) Tanner, S. F., 302, 336(364) Taranto, M. V., 411, 423(1042) Tarassenkov, D. N., 298, 335(327) Taskar, S. P., 412, 424(1072) Tasurni, M., 286, 332(208) Tatarov, P. G., 297, 334(311) Tatsumoto. N., 375, 417(777) Taubert, R., 412, 425(1095) Tauret, C., 412, 424(1073) Tawashi, R., 308, 337(421)

455

Tay, M.E., 202,204,229,232, 233, 236, 237, 239,240,258(6, 26), 260(79) Taylor, R. B., 75,95,138(188) Taylor, R. J. K., 187, 188, 199(147) Taylor, T. C., 367, 416(742) Tei, S., 70, 137(157) Teitelbaum, R. C., 275, 286, 287, 288, 330(128) Temperini, A., 162, 197(67) Terajima, K., 307, 337(411) Terayama, H., 408,422(998) Thakkar, A. L., 381,383,417(801) Thang, T. T., 124, 125, 142(325) Thangarasa, R., 20, 24,25,27, 28, 29, 30, 31, 35,36, 37, 41, 54, 56, 67, 98, 134(33, 38, 39,41,42, 44,60), 135(90), 136(145, 145a), 137(149) Thieffry, A., 24, 30, 32, 35, 36, 49, 50, 51, 55, 62, 72, 74, 75, 80, 113, 116, 117, 123, 134(43, 63), 135(76) Thiem, J., 115, 141(309) Thoma, J. A., 270,272, 274, 275, 329(75), 330(109), 409,412,423(1018), 424( 1065) Thomas, E. J., 113, 141(303) Thomas, G. J., 280,331(165) Thompson, C. R., 148, 196(38) Thompson, J., 249, 260(92), 296, 333(269) Thompson, J. K., 148, 196(35) Thorpe, P. H., 298, 335(325) Tidbury, R., 186, 187, 198(123) Tiecco, M., 162, 197(67) Tiffin, A. J., 397, 399,419(884) Tillotson, J. A.. 313, 338(450), 350, 373, 414(669) Timoshenko, N. V., 297, 335(318) Tingoli, M., 162, 197(67) Tipson, R.S., 180, 197(97a) Tirendo, S., 52, 136(121) Tisnks, P., 105, 106, 107, 140(272) Titcomb, S. T., 398,411, 419(885) Tittle, T. V., 217, 259(54) Tius, M. A., 19, 113, 133(14) Toa Gosei Chemixcal Industry Co., Ltd., 413, 425(1111) Tobe, T., 56, 136(144) Tobin, R., 319, 321, 339(516), 360,414(690) Todd, J. W., 325, 341(594) Toepfer, A., 116, 141(315) Toerien, F., 106, 141(289)

456

AUTH()R INDEX

Toguchi, H., 399,419(889) Tokuda, M., 413,426(1129) Tokumura, A., 371, 416(754) Tolmasquim, E., 296,333(272) Tolstoguzov, V. B., 406, 407, 408, 411, 422(984, 985, 989, 990). 423(1039, 1040, 1041,1044) Tomasik, P., 263, 264, 268, 271, 272, 301, 302, 303, 313, 316, 320, 325, 326, 328(3), 329(62, 83, 84), 336(353, 355, 379), 338(459), 342(611, 626). 345, 351, 352, 354, 357, 358, 359, 360, 367, 372, 373.374, 383, 386,402, 404,414(677, 678,683,684,689), 416(755), 417(807), 420(926), 421(955) Tomaszewski, M. J., 80. 139(229) Tominaga, Y., 239,245,246,247, 260(82, 83, 88, 89, 91) Tomioka, I., 44.45, 46, 48, 135(94) Tomita, G., 383, 417(806) Tomita, M., 79, 139(216) Tomita, S., 307, 337(411) Tomka, J., 399,419(890) Toppan Printing Co., Ltd., 411, 424(1058) Torii, Y., 273, 294,330(99), 364,415(716) Tornel Osorio, P. L., 84, 98, 139(247) Torssel, K., 186, 187, 198(134) Toth, M., 283, 332(198), 363,415(709) Tovbin, M., 279, 331(156) Tran, V., 266,267, 303, 329(51, 52) Traquair, J., 412, 425(1090) Tregubov, N. N., 319, 340(531), 410, 423( 1031) Tretyakov, G. N., 301, 335(349) Trimnell, D., 324, 341(587) Trogus, C., 373,416(765) Tromp, E., 412, 424(1086) Tronchet, J. M. J., 177, 197(91) Trost, F., 325, 341(599) Trott, G. F., 408, 422(1003) Trubell, 0. R., 361,369,415(701) Trumtel. M., 52, 136(118) Truscello, A. M., 41.76, 95, 97, 111, 115, 118, 120, 121, 123, 135(86, 87) Tsai, C.-M., 255, 261(106) Tsang, R., 55, 136(139) Tsao, G. T., 307, 337(409, 410) Tschimirov, J. I., 411, 423(1044) Tsubakimoto, T., 366, 415(711) Tsuchikashi, S., 272, 284, 329(92)

Tsuchiya, T., 180, 197(97b) Tsuda, Y., 33, 35, 36, 49, 50, 51, 53, 54, 55, 56, 57, 64,65, 75, 77, 81, 84, 85,105. 106, 110, 114, 115, 117, 118, 123, 134(70), 135(77, 78, 106), 136(130, 131) Tsuge, H., 396, 419(876) Tsutsumi, C., 308, 337(418) Tsutsumi, N., 114, 141(307) Tuckmantel, W., 83, 139(240) Tupciauskas, A. P., 19, 35, 133(23) Turner, H. A., 322,340(557) Turner, J. H., 400, 420(902) Turner, N. C., 264, 328(30) Tyagi, M. P., 186, 187, 198(134) Tyler, P. C., 70, 105, 137(158), 140(281, 282)

U Ubertis, B., 304, 307, 336(389) Udodong, U., 170, 197(84,85) Ueda, S., 303, 336(367), 409, 410, 422( 1012), 423(1014) Ulmann, M., 300,301,309,311,325, 335(346, 347). 336(356), 338(435, 446, 438), 341(601, 602). 348, 351, 353, 354, 357, 359, 363, 365, 366, 367, 371, 412, 414(659, 682), 424(1067) Umezawa, H., 184, 198(99) Umezawa, S., 184, 198(99) Undritz, E., 326, 342(629) Urban, J. L.. 249, 260(93) Urqhart, A. R., 305,307,337(399) Uteza, V., 33, 86, 134(71)

V Valmet, E., 235, 260(76) Valverde, S., 19, 133(15-17) van Boeckel, C. A. A., 73, 137(163) van Boom, J. H., 54, 55, 65, 73, 79, 82, 83. 85, 102, 103, 106, 110, 117, 136(135, 136), 137(165, 166, 176), 139(218,219, 222, 236, 237), 140(254), 170, 173, 174, 177, 197(81, 83, 86, 87) Van Delft, F. L., 85. 140(254) Van der Berg, C. F. S., 302, 336(363) van der Hoeve, J., 299,320,335(338), 340(535)

AUTHOR INDEX

van der Klein, P. A. M., 54, 55, 65, 79, 85, 136(135, 136), 139(222), 140(254), 170, 173, 197(81,83, 86) van der Marel, G. A., 54, 55, 65, 73, 79, 82, 83, 85, 102, 103, 106, 110, 117, 136(135, 136), 137(165, 166, 176), 139(218, 219, 222,236, 237), 140(254), 170, 173, 174, 177, 197(81, 83, 86, 87) van der Meer, P. H., 170, 173, 197(81, 83) van der Merwe, T. L.. 33, 135(72) van Dyk, M. S., 36, 84, 98. 135(81) Van Es, T., 148. 149, 180, 181, 182, 196(27-34) van Heerden, F. R., 33, 135(72) van Lengerich, B., 369, 370,390,392, 393, 416(748,749), 418(857) van Lonkhuysen, H., 395, 396,419(865) van Ritter, H. R. P., 76, 138(192) van Straten, N. C. R., 79, 106, 110, 139(219) Vanderberghe, H., 296,333(233) Vanino, L., 266, 329(57) Vannucchi. A., 123, 142(324) Vargas, F., 255, 261(107) Varma, A. J.. 80, 139(223) Vasella, A., 49, 50,51, 53, 61, 68, 69, 72, 77, 96, 97, 101, 103, 135(107) Vasileva, L. Yu., 301, 306,336(351, 352), 337(405) Vattle, J.-M., 46, 135(102), 186, 187, 198(132, 133) Vauzeilles, B., 192, 199(156) Veeneman, G. H., 73, 137(165) Veiga, M. F., 400, 420(907) Veksler, B. A,, 316, 339(485) Vendrely, R., 404, 421(958) Venkatararnan, K., 268, 269,270,279, 296, 313, 322, 329(69), 340(556), 378,383, 41 7(796) Verduyn, R., 54, 65, 82, 83, 136(136), 139(237) Verez Bencomo. V, 184, 198(100) Verheyden, J. P. H., 17, 86, 99. 100, 133(1) Verlag, G. T., 144, 195(3a) Vesely, V., 404.42 1(960) Veyritres, A,, 26, 32, 34, 42, 50,52, 55, 72, 73, 74, 75, 76, 80, 106, 116, 117, 129, 134(57, 63). 136(118, 137), 137(172), 138(191), 141(291, 314), 142(347) Vlahova. I. R., 117, 141(322) Vlahova, P. I., 117, 141(322)

457

Vliegenthart, J. F. G., 76,138(192) Voelgyi, P., 412, 425(1092, 1093) Vogel, A., 266, 329(50) Vogel, C., 72, 96, 137(162) Vogel, K., 126,142(339) Volarovich, M. P., 301, 306, 336(352), 337(405, 415) Volrnan, D. H., 308, 337(416) Vonderviszt, F., 275, 330(126) Vrbaski, T., 316, 339(479) Vuk, M., 410,423(1036) Vullette, P., 412, 424(1079)

W Wada, K., 320,326,340(540) Waelti, A., 324, 341(581) Wagner, D., 17, 86, 99, 100, 133(1) Wagner, G., 145, 146, 148, 195(15-20). 196(22-23, 25, 26) Wagner, J. A., 367,416(734) Wagner, J. E., 251, 260(97) Wagner, P., 73, 137(173) Wahl, A. S., 412,424(1059) Waldschmidt-Leitz, E., 270, 274, 296, 329(78), 330(115) Waller, S. C., 44,45,46, 47, 135(101) Wang, P. C., 153, 196(52, 53) Wang, V. R., 44,45,46,48, 135(100) Wang, Y., 177,197(93) Wang, Y. J., 372,404,416(755), 421(955) Ward, P., 77, 138(198) Warren, L., 219, 259(59) Washnuettl, J., 383, 417(805) Wasylishen, R. E., 20,24, 27, 30, 133(31), 134(33, 39) Watanabe, F., 264, 328(12) Watanabe, T., 271, 329(80), 386,418(827) Watson, C. A., 405, 421(968) Watson, F. S., 265, 328(41) Watson, S. A., 296, 334(276), 396, 419(875) Webking, F. W., 325, 342(606) Wedlock, D. J., 245, 260(86) Wehrli, H. P., 386,418(823) Wei, A,, 105, 140(278) Weidinger, A., 317,339(493), 384,417(812) Weigel, E., 361, 363, 415(698) Weigel, H., 397, 399, 419(884) Weinert, J. A. G., 400,420(898) Wells, E. J., 20, 133(29)

458

AUTHOR INDEX

Welzel, P., 73, 137(173) Wendt, B., 325,341(601), 412, 424(1067) Werner, G. A,, 396, 398,419(869) Wessel, H.-P., 115. 141(309) West, C. D., 286, 313, 332(205) Westerduin, P., 73, 137(163) Westman, J., 52, 106, 136(117) Wetzel, P., 73, 137(167) Whang, D., 63, 137(146) Wheatley, J. M., 296, 333(268) Whelan, W. J., 268, 274, 275, 280, 284, 316, 329(64), 330(114). 331(165), 339(482), 348,351,355,363,414(657) Whistler, R. L., 144, 148, 195(3e), 196(28), 275, 278,296,330(118), 331(150), 334(276), 357, 363, 386, 396, 414(687), 418(824), 419(875) White, A. H., 74, 137(179) White, R. F. M., 20, 26, 134(34) White, V. A., 403,421(945) Whittenberger, R. T., 402,403,420(929) Wiejak, S., 264, 271, 301,302, 328(3), 336(353, 355) Wilberg, E., 296, 333(267) Wilchek, M., 202, 258(12) Wilham, W. L., 381, 383,417(801) Williams, C. B., 369, 371,416(751) Williams, E., 184, 198(105, 106) Williams, M. R., 387, 418(841, 842) Williams, P. A., 245, 260(86) Williams, V. R., 269, 290, 329(72) Williamson, A. R., 235, 260(77) Wilson, E. J., 280,331(182) Wilson, T., 188, 199(148) Winchester, B. G., 70, 137( 158) Wing, R. E., 324, 341(587) Winkler, C. A., 304, 305, 309, 311, 336(390), 337(401, 427), 357,414(686) Winkler, S., 296, 333(247) Winkler, T., 187, 188, 189, 199(144) Witczak, Z. J., 143, 144, 195(3e, 3f) Witham, T. F., 206, 211,213, 222, 223, 224, 259(33,63) Witham, T. W., 213, 242,259(49) Wittman, M. D., 79, 106, 118, 138(210) Wittwer, F., 399, 419(890) Witzel, T., 187, 199(142) Wolf, R., 277, 290, 291, 292, 293, 331(140) Wolff, E., 366,415(723) Wolff, 1. A., 296, 334(278)

Wolters, I., 302,336(363) Wondolowski, L., 412,424(1064) Wong, E., 242, 259(46a) Wong, R. Y., 393,400,419(871) Woodruff, S., 400, 402, 403,420(908, 924) Woodside, E. E., 408, 422(1003) Woodward, S., 47, 135(104) Wooten, J. C., 397, 419(882) Wrackmeyer, B., 19, 35, 133(24) Wrede, F., 144, 145, 195(7-10, 12, 13) Wright, A,, 278, 284, 331(146) Wright, A. J., 386, 418(821) Wright, B. E. G., 235, 260(77) Wright, C. W., 405, 422(977) Wright, H. B., 412,424(1065) Wright, H. E., Jr., 406,422(980) Wright, L. M., 323, 341(572) Wright, V. R., 277. 331(143) Wu, X., 51,78,96,136(112), 138(203) Wurster, D. E., 303,305,336(381), 337(402) Wurzburg, 0. B., 322, 341(561) Wyler, R., 353,366,414(679)

X

Xin, Y. C., 192, 199(155)

Y Yabumoto, Y., 306, 308,337(407) Yadav, J. S., 44,46, 135(98, 99) Yagi, K., 407, 422(992) Yajima, H., 268, 275, 283, 286, 290, 329(61), 330( 131) Yakhina, F. Kh., 297, 335(312) Yakovkina, E. A., 311,338(442), 349,360, 414(662) Yakovkina, Ye. A., 300,335(342) Yakshinskii, A. I., 281,332(193) Yamada, T., 413,426( 1128) Yamaguchi, K., 299,306, 308, 312, 335(329), 337(407) Yamaguchi, S., 84, 139(249) Yamamoto, D., 373,416(761) Yamamoto, H., 303, 336(371) Yamamoto, M., 281, 332(191), 375, 4 17(777) Yamamoto, S., 297,334(306) Yamamoto, Y., 297, 334(306)

AUTHOR INDEX Yamamura, H., 117, 141(321) Yamarnura, I., 411,423(1038) Yamamura, S., 78, 87, 138(206), 140(261) Yarnanaka, M., 399, 419(889) Yarnauchi, J., 413, 425(1113, 1114) Yamazaki, W. T., 403, 404,421(934, 954) Yang, D., 79, 126. 127, 139(221) Yang, G., 19, 77, 80, 81, 133(11) Yang, J. W., 113, 141(305) Yang, Y., 374, 417(774) Yasuda, K., 25, 29, 134(55) Yasurnatsu, K., 386, 418(837) Yasunaga, T., 281, 332(191), 375,417(777) Yasunatsu, K., 367, 416(731) Yates, J. B., 186, 198(116) Yelton, D. E., 202, 258(8) Yenson, M., 374,376,417(779) Yerian, H. J., 275, 330(118) Yin, G. K., 374,417(774) Yishen, Z . , 326, 342(628) Yogai, S., 186, 187, 198(125) Yokokawa, Y., 84, 139(249) Yokoyarna, Y., 184, 198(105),413, 426( 1136) Yoshida, A., 278, 280, 331(151) Yoshida, S., 280, 331(173, 174, 177) Yoshikawa, M., 84, 139(249) Yoshimoto, K., 53, 55, 64,75, 77, 81, 84, 85, 105, 106, 110, 117, 118, 136(130, 131) Yoshimura, J., 78, 104, 105, 138(207), 140(275, 283) Yoshinaga, M., 56, 136(144) Yoshioka, T., 87, 100, 140(260) Yoshitomo, A., 101, 140(264) You, D. M., 177, 197(94) Young, W. W., Jr, 253, 261(103) Youssef, R. H., 72, 137(159) Yovanovitch, D., 300,335(343,344) Yovanovitch, O., 303, 315, 336(375), 338(470,471) Yu, D. T., 321, 340(544) Yu, K.-L., 52, 63, 82, 136(126) Yurin, 0. V., 411,423(1048)

459

2 Zagrodzki, S., 400,420(903) Zak, V. I., 297, 335(313) Zapata, A., 83, 102, 139(246) Zawadzki, W., 352,383, 414(678), 417(807) Zborowski, J., 413, 425(1108) Zedde, C., 105, 106, 107, 140(272) Zegelaar-Jaarsveld, K., 73, 79, 102, 103, 106, 110, 117,137(166), 139(218,219) Zeitlin, H., 364,415(715) Zhang, Z., 52, 54, 70, 72, 96, 101, 103, 136(120, 134) Zhou, S., 19, 77, 80, 81, 133(11) Zhuravel, P. V., 301, 336(350) Zhuravleva, E. I., 304, 305, 307, 336(386), 337(398) Zhuravleva, Z. D., 410,423(1031) Zhushman, A. I., 322,340(552), 410, 423( 1031) Ziegast, G., 276, 279, 285, 286, 287, 330(136), 331(152) Ziegler, T., 79, 139(220) Zillmann, E., 367,416(744) Zima, G., 186, 187, 192, 198(139), 199(152) Zimmermann, W., 145, 195(13), 249, 260(92) Zinder, N. D., 234, 260(75) Zingaro, R. A., 144, 148, 149, 195, 195(2, 3b, 6), 196(35-42) Zobel, H. F., 363,402,411,412, 415(708), 420(923), 424(1056, 1064) Zografi, G., 381,383, 417(802) Zopf, D. A., 204, 255, 258(25), 261 (106) Zubchenko, A. V., 400,420(906) Zubkova, S. M., 297, 335(319) Zucker, B., 277, 331(141) Zugenmeier, P., 276,277,304, 330(134), 336(384) Zuurmond, H. M., 54,55,65,73,79, 136(135), 137(165), 139(222), 170, 173, 197(81, 83, 86) Zwikker, J. J. L., 376, 380, 417(791)

This Page Intentionally Left Blank

SUBJECT INDEX A

SDS with, 375-376 separation, 297 in starch, 268-269,271 structure, 346 Anti-carbohydrate antibodies N-acetyl-P-o-glucosamine, 230-231

N-Acety1-/3-D-glucosamine antibodies,

230-231 N-Acetyb,h-glucosamine-l -P, 252-253 Acridine Orange, 383-384 Acyclic diols, 129-131,133 Affinity absorbents, 203-204 Affinity chromatography anti-carbohydrate antibodies, 203-209 protocol for, 204-205 Agar diffusion, 205-206 Alcohols organic complexes, 360-361,363-364 starch complexes, 283 Aldehydes, 365-366 Alginate complexes, 411-412 Aliphatic hydrocarbons, 352-353 Alkenylations, 180-186 Alpha amylases, 409 Aluminate complexes, 325-326 Amines, 373-374 Ammonium salts, 322-326 Amylopectin alumina and, 325 binding capacity, 280 composition, 296 coumarin with, 373 decoiling, 349 -iodine interaction, 277-278 monoglycerides and, 396-399 pyridine with, 373-374 in starch, 268-269 structure, 348 Am ylose alcohol effects, 360-361,363 alumina and, 325 binding capacity, 279-280 carboxyamides. 374 composition, 296 coumarin with, 373 decoiling, 349 diffraction patterns, 359 fatty acids with, 371-372 fractionation. 297 hydrolysis, 282-283 -iodine interaction, 276-277 pyridine with, 373

N-acetyl-P-o-glucosamine-I-P, 252-253 analysis, 255-256,258 analytical methods, 203-209 BSA, 223-224 characterization, 201-203 fucose, 223-224 galactose, 218-219 galacturonic acid, 227,229 GlcA-Rha, 236,238-240 glucoamylase, 247-249 glucose, 214-215,217 glucose-I-P, 251-252 glucuronic acid, 224-226 gum arabic, 242-246 immunization, 212-213 isomaltose myeloma protein, 240-242 lactose, 231-233,235-236 a-o-mannose, 219-220 preparation, 209-212 rhamnose, 229-230 Shigella flexneri lipopolysaccharides, 254 1-thio-a-o-mannose, 220-223 tumor, 249-250 utility, 255-256 xanthan, 246-247 xylose, 226-227 yeast mannan, 254-255 Arabinopyranoside, 98 Aromatic hydrocarbons, 352-353 Arrhenius acids, 313-314 Ascorbic acid, 296 Aspergillus niger, 211

2-Azido-2-deoxy-glucopyranoses, 167-170 Azido-phenylselenylation, 161-167

B Barium salts, 315 Bases, 313-314 Bengal Rose, 384 Benzene, 271

461

462

SUBJECT INDEX

Benzeneselenyl triflate, 191-192 Benzylation, 61 Boric acid, 293 Bovine serum antigens, 223-224 1-Butanol, 361 Butanone. 367

C

Calcium chloride, 323-324 Carbohydrates anti, see Anti-carbohydrate antibodies lipids and, 400 tin-containing intermediates, see Organotin Carboxyamides, 374 Carboxylic acids, 296,367-372 Carboxylic esters, 372-373 Carcinoembryonic antigens, 250 CEA, See Carcinoembryonic antigens Cellulose, 412-413 Cellulose sorption, 384 Cerium salts, 327 Chloral, 365-366 Chlorocresols, 364-365 Chromatography, see Affinity chromatography Coloration scales, 376,378 Congo Red, 384 Coumarin, 373 Crystallinity, 303 Cyclization mediated reactions, 186-188 radical, 188-191 a-Cyclodextrin. 313 Cyclomaltohexaose, 313

2,2-Dibutyl-l,3,2-dioxastannolane structure, 30-32 Dibutylstannylene acetals alkylation, 63,98 benzoylation, 131 as glycosyl acceptors, 126-127 near deoxy centers, 103-110 near double bonds, 103-110 nomenclature, 18-19 reactions, 32-33 regioselectivity, 65-68,95-97 terminal diols, 120-121 Dibutyltin oxide, 19 Dichroism, 288-290 Diffusion, agar, 205-206 Digestibility, 399-400 N,N-Dimethylformamide, 374 Dimethyl sulfoxide, 359-360 Diols acyclic, 129-131,133 near deoxy centers, 103-110 near doubled bonds, 103-110 symmetrical, 44 terminal, 110,119-124 cis-Diols, 71,95-100,103 fruns-Diols, 44,61-68 2,2-Dibutyl-l,3,2-dioxastannolane structure, 27 Disinfection, 297-298 Dyes anionic, 381,383 cellulose sorption, 384 coloration scales, 376,378 neutral, 378,381

E D

Dehydration, 300-301 2’-Deoxy nucleosides, 158-161 Deoxy sugar synthesis, 186-188 Dextrin complexes, 411-412 Dialkylstannylene acetals regioselectivity, 36-44 structure, 26-32 Dialkyltin dialkoxides nomenclature, 18 structure, 26-32

Electrofocusing, 206 Electrolyte effects, 272 Electron resonance spectroscopy, 287-288 Electrophoresis, 206 Ethanol, 360-361 Ethers, 365

F Fatty acids, 371-372,386-387 Fructopyranoside, 98

SUBJECT INDEX Fucose antibodies, 223-224 Furanoses, 99-100, 167-170

G Galactose antibodies, 218-219 Galacturonic acid antibodies, 227, 229 Gelatinization, 402-405 Gelation, 378 Gel isoelectrofocusing, 206 Glucoamylase, 21 1, 247-249 Glucose antibodies, 214-215, 217 Glucose-1-P, 251-252 D-Glucosylselenophosphates, 152-154 Glucosyluronate-rhamnose, 236, 238240 Glucuronic acid, 224-226 Gluten, 398 Glycals. 154-158 Glycoconjugate isolation, 21 1-212 Glycolipids, 397-398 Glycoprotein isolation, 210-21 1 Glycoside formation, 124, 126-129 Glycosylation ribofuranoside, 174 selenoglycosides in, 167-170 Glycosyl donors, 170-177 cis-Glycosyl esters, 126 Gums arabic antibodies, 242-246 polysaccharide, 41 1-412

463

history, 264-266 organic compound effects, 272-274 origins, 268-270 physical properties, 284-292 preparation, 266-268 protein effects, 272-274 solvent effects, 270-272 state, 268-270 structure, 274-278 Iron-starch complexes, 326-327 Isomaltose myeloma protein, 240-242

K Ketones, 366-367

L Lactose antibodies, 231-233, 235236 Langmuir, 381 Lecithin, 388 Lipid-starch complexes characteristics, 385-386 digestibility, 399-400 functional properties, 396-399 native, 386-387 preparation, 387-388,390-392 properties, 392-393, 395 structure, 392-393, 395 Lipopolysaccharides, 254 Lysophosphatidylcholine, 386

H Haloalkanes, 357 Halobenzenes, 357 Hydrocarbons, 352-353

I Immunization, 212-213 Infrared spectroscopy, 286 Iodine-starch complexes alcohol effects, 283 applications, 296-298 chemical properties, 293-294. 296 electrolyte effects. 272 formation. 278-284

M a-D-Mannose antibodies, 219-220 Menthone, 367 Metals hydroxides, 314-316 nontransition, 322-326 transition, 326-327 Methylation, 61-62 Methylene Blue, 381, 383 1,2-cis-Methyl glycosides, 124, 126 Methyl P-D-xylopyranoside, 67 Monoglycerides, 396-397 Monosaccharides, 400-405 Mossbauer spectroscopy, 287

464

SUBJECT INDEX

N Nitrogen-based compounds, 358 Nontransition metals, 322-326 Nuclear magnetic resonance I3C, 25,288 'H, 288 i'9Sn, 19-20 Nucleophlic displacement, 148-

Potassium selenocyanate, 148-150 Precipitin, 222 Protein-starch complexes characteristics, 405 native, 405-406 synthetic, 406-411 F'yridine, 373-374

150

R 0

Oligosaccharides, 400-405 Optical rotatory dispersion, 290 Organoselenium chemistry, 143-145 mediated alkenylations, 180-186 Organotin analysis, 19-22,25 nomenclature, 18 preparation, 18-19 reactions, 32-33 regioselectivit y factors, 33-44 trends, 44,60-68 structures, 25-32

P Pectins, 411-412 Pentoglycans, 401-402 Phenols, 364-365 Phenyl 2-azido-2-deoxy-selenoglycosides,

163 N-Phenylselenophthalimide,184 2-Se-Phenyl-2-selenoglycosylazides, 162-163 2'-Se-Phenyl-2'-selenodisaccharides, 154-157 Phenyl selenoribofuranoside, 174-177 Phenylselenylation, 154-158 Polymer complexes, 413 Polyols cis-diols-containing, 71,95-100,103 (ram-diols containing, 44,61-68 Polysaccharide gum, 411-412 Polysaccharides -iodine interaction, 277 isolation, 209-212

Raman spectroscopy, 286-287 Regioselectivity factors, 33-44 trends, 44,60-68 Rhamnose antibodies, 229-230 Rheology, 292 Ribofuranoside. 174

S Salts, 316-322 SDS, see Sodium dodecylsulfate Selenium, 144-145 Selenodisaccharides, 177-180 Selenoglycosides, see also specific sugars chemistry, 143-145 cyclization-mediated reactions, 186-188 0-glycosidation with, 170 glycosylation by, 167-170 as glycosyl donors, 170-177 nucleophlic displacement, 148-150 opening, 150-154 phenylselenylation, 154-158,161-167 preparation, 145-148 tethered approach connection, 300-301 Selenolactonization, 191-192 Shigella flexneri lipopolysaccharides, 254 Sodium aluminate, 325 Sodium chloride, 322-323 Sodium dodecylsulfate, 375-376 Sodium salicylate, 319 Solvent effects, 270-272 Sorption, 304-307,312-313 Spectroscopy "C NMR, 25 electron resonance, 287-288 infrared, 286 M(lssbauer, 287 Raman. 286-287

SUBJECT INDEX 119311 NMR, 19-20 UV, 284-285 visible, 284-285 Starch -alginate complexes, 41 1-412 -cellulose complexes, 412-413 derivatives, 411-412 -dextrin complexes, 411-412 -guest complexes alcohols, 360-361, 363-364 aldehydes, 365-366 amines, 373-374 ammonium salts, 322-326 Arrhenius acids, 313-314 bases, 313-314 carboxyamides, 374 carboxylic acids, 367-372 carboxylic esters, 372-373 dyes with, 376-385 ethers, 365 formation, 348-349 haloalkanes, 357 halobenzenes, 357 hydrocarbons, 352-353 ketones, 366-367 metal hydroxides, 314-316 monosaccharides with, 400-405 nitrogen-based compounds, 357, 358 nontransition metals, 322-326 oligosdccharides with, 400-405 phenols, 364-365 preparation, 350-352 salts, 316-322 sorption. 312-313 structures, 263-264, 346-348 sulfates, 375-376 sulfur-containing, 3.59-360 vitamins, 374-375 -iodine complex alcohol effects, 283 applications, 296-298 chemical properties, 293-294, 296 electrolyte effects. 272 formation, 278-284 history. 264-266 organic compound effects, 272-274 physical properties, 284-292 preparation, 266-268 protein effects, 272-274 solvent effects, 270-272

465

starch origins, 268-270 state, 268-270 structure, 274-278 -iron complex, 326-327 -lipid complexes characteristics, 385-386 digestibility, 399-400 functional properties, 396-399 native, 386-387 preparation, 387-388, 390-392 properties, 392-393,395 structure, 392-393 -polymer complexes, 413 -polysaccharide complexes, 411-412 -protein complexes characteristics, 405 native, 405-406 synthetic, 406-411 -water complex analysis, 310-312 binding capacity, 320-321 problems, 298-300 sorption, 304-307 starch origins, 307-310 water in, 300-304 Streptococcus faecalis, 212-213 Streptococcus mutans, 204-205 Sugars filtration, 402 selenium-containing, see Selenoglycosides Sulfates, 375-376 Sulfonates, 375-376 Sulfonic acids, 359-360 Symmetrical diols, 44

T Tethered approach connection, 300-301 I-Thio-a-D-mannose, 220-223 Tin intermediates, see Organotin NMR spectroscopy, 19-20 p-Toluenesulfonylation, 37-38 Transition metals, 326-327 Tributylstannyl ethers as glycosyl acceptors, 126-127 nomenclature, 19 reactions, 32-33 regioselectivity, 33-36, 65-68, 95-97 terminal diols. 120-121

466

SUBJECT INDEX

Tributyltin ethers, 25-26 Trichloroacetaldehyde, 365366 3,4,6-Tri-O-acetyl-I,2-anhydro-m-~glucopyranose, 150-152 Tumors antibodies, 249-250 glycoproteins in, 210-21 1

W Water-starch complex analysis, 310-312 problems, 298-300 sorption, 304-307 starch origins, 307-310 water in, 300-304

U Ultracentrifugation, 206-208 Ultraviolet spectroscopy, 284285

X Xanthan, 246-247 X-Ray diffraction, 290 Xylose antibodies, 226-227

V Vanillin, 366 Visible spectroscopy, 284-285 Vitamins, 374-375

Y Yeast mannan, 254-255