The Biology-Chemistry Interface

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The Biology-Chemistry Interface A Tribute to Koji Nakanishi edited by Raymond Cooper Pharmanex, Inc. San Francisco, California John K. Snyder Boston University Boston, Massachusetts

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ISBN: 0-8247-7116-8 This book is printed on acid-free paper. Headquarters Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016 tel: 212-696-9000; fax: 212-685-4540 Eastern Hemisphere Distribution Marcel Dekker AG Hutgasse 4, Postfach 812, CH-4001 Basel, Switzerland tel: 41-61-261-8482; fax: 41-61-261-8896 World Wide Web http://www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the headquarters address above. Copyright © 1999 by Marcel Dekker, Inc. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher. Current printing (last digit): 10 9 8 7 6 5 4 3 2 1 PRINTED IN THE UNITED STATES OF AMERICA Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Preface Natural products science, a fascinating cornerstone of modem research, has long bridged the traditional frontier between chemistry and biology. Humankind has always been intrigued by the power and potential of plants and nature. Many old texts reveal how the ancient cultures drew on the beneficial properties of plants. They learned the wisdom of extracting the ingredients and using such potions as foods, medicines, and mood enhancers long before anyone understood how these worked. Slowly we have found the tools to explore the chemistry of these ingredients, and thus the systematic study of natural products began. Morphine was isolated in 1805 and strychnine in 1819, although their structures remained mysteries for more than 100 years, and pure camphor has been an article of commerce for centuries. Today the biosynthetic machinery of plants and other organisms is purposefully manipulated to produce new "natural products" of biological significance in medicine and agriculture. In the nineteenth century, early progress in natural products research centered on the study of pigments from flowers as colored dyes. Originally, extraction of drug compounds, particularly alkaloids, from plants was achieved by using simple isolation methods: a water steep or a solvent (generally alcohol) extraction. The impetus was set to explore this research area further and, not surprisingly, more and more intellectual pursuit of natural sciences and our environment encouraged universities and scientific centers throughout the world to study natural products, which then formed the nucleus of chemistry programs. As source material to begin any research investigation, plants were abundant and easily obtained. The first natural products to be studied in detail were generally the major constituents of plants, since these often precipitated from solution and could be purified through recrystallization. How well do we recall Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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today that the purity of chemicals up to the latter half of the twentieth century was determined solely by melting point? As increasing numbers of chemical constituents with more complexity were found, structural analysis relied on chemical transformations and degradation studies. Total synthesis was confirmatory. The discovery of one or two compounds based on these research studies was usually acceptable to earn a doctorate. The second half of the twentieth century has witnessed incredible advances in natural products research. These have been achieved through the discovery of new chromatographic separation methods and remarkable advances in spectroscopy. As new technologies for isolation and structure identification have evolved, the isolation and detection of ever-diminishing amounts of natural products, coupled with the determination of structures on a microscale, have become almost routine. In addition to identifying important targets for total synthesis, and thereby spurring innumerable advances in fundamental organic chemistry, studies of natural products have led to significant research efforts in the related fields of bioorganic chemistry and biosynthesis, as chemists, biologists, and biochemists have striven to understand how these molecules are produced in nature and to establish the molecular basis of the biological activity of these compounds. The structural determination of natural products has impacted our basic understanding of nature. One very important aspect of structure determination is the use of spectroscopy, particularly nuclear magnetic resonance, mass spectrometry, circular dichroism, and x-ray diffraction methods. Circular dichroism is particularly important in establishing absolute stereochemistry, as chirality is correlated directly to biological activity of the biomolecule. Thus, as we approach the end of this century, we see the challenging questions in biology requiring answers at the molecular level being met by increasingly sophisticated techniques and comprehension of the chemistry of nature. Professor Koji Nakanishi has been a pioneer and a towering figure in natural products research. He has been a major contributor at the crossroads of bioorganic chemistry over the past 40 years. His extraordinary and broad vision of natural products chemistry and its close relationship to bioorganic studies is now universally accepted and was the inspiration for this book. He has constantly looked at challenges in bioorganic chemistry and pushed ever closer the boundaries at the interface between chemistry and biology. He has achieved this through his lifelong studies in natural products, his investigations into the chemistry of vision, his pursuit of new and ever more powerful analytical and spectroscopic microtechniques for solving complex structural problems, and his study of infrared and circular dichroism and their applications to bioorganic science. Koji's curiosity and insights in applying the right solution to challenging problems are among his legacies, to which we as students of his are deeply grateful. Koji Nakanishi was born in 1925 in Hong Kong to parents of Japanese Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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descent. As a result of his father's business postings abroad, Koji's early childhood was spent in various European capitals as well as in Alexandria, Egypt, thereby giving birth to and nurturing his unique world vision. He returned to Japan for his formal university training and received his B.Sc. degree at Nagoya University in 1947. He first came to the United States in 1950–52 to study with the legendary Professor Louis Fieser at Harvard University, and he returned to Japan as an assistant professor to embark on his remarkable career in natural products and bioorganic chemistry. He completed his Ph.D. in 1954 under the mentorship of Professors Egami and Hirata, then took positions at Nagoya University (1955–58), Tokyo Kyoika University (1958–63), and Tohoku University (1963–69). In 1969 he was invited to join the faculty at Columbia University, New York, where he currently holds the chair of "Centennial Professor of Chemistry." Indeed, it was at Columbia University that former and current students, postdoctoral fellows, and esteemed colleagues of Professor Nakanishi gathered to celebrate his 70th birthday and to honor him for his years of mentorship and friendship, as well as for his considerable contributions to bioorganic science. Two days of stimulating presentations on various topics in bioorganic chemistry gave birth to the idea behind this book: to produce a volume with contributed chapters from his former students in his honor. This text reflects Koji's own research interests in its scope and attempts to bridge the gap between biology and chemistry: a gap that is rapidly diminishing as investigators use the tools and vision that Koji has provided. Koji humbly reminds us that he is "only a technician"; we respectfully differ. He is a visionary, and in essence the investigatory seeds planted by Koji are now in full bloom in research gardens headed by those he taught. We choose to highlight current research activities from former members of his research groups from Asia, the United States, Europe, and Australia, thereby illustrating Koji's global scientific influence. As with Koji's own research, one goal of this text is to further dissolve the boundary that has kept chemistry and biology apart; the contributions in this volume are by investigators for whom this boundary has long since disappeared. It is hoped that readers will come to understand the highly interactive nature of research in biological chemistry and chemical biology, and find the transition between chemistry and biology far less intimidating. Thus, this book reflects the ideals of Professor Nakanishi and his impact. Although the chapter titles may at first glance seem to suggest a relatively large breadth of subjects, in fact they all fit snugly within the focus of the chemical basis of biological activity. Subjects range from hydrolytic enzymes to combinatorial chemistry, yet all the chapters strive to elucidate biological responses at the molecular level. The contributing authors provide detailed accounts of their current research rather than presenting formal reviews of disparate subjects. The Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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rationale for this approach is to emphasize the interactive nature of the research in bioorganic chemistry. The unifying theme throughout is the original skills that developed in natural products research and chemistry of vision. The microanalytical techiques, the spectroscopic challenges, have now evolved into the application of chemical minds to biological problems. Thus, the selection of authors reflects a blend of investigations in academic and industrial research. Koji's pioneering contributions and world vision of science have inspired several generations of chemists from around the globe, and demonstrations of his mastery of the magical arts have left numerous audiences of the brightest minds completely and delightfully mystified. We can identify the defining moment of our education and scientific growth as the time we spent with Koji, and we offer our profoundest gratitude to him for his tireless leadership and support. RAYMOND COOPER JOHN K SNYDER Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Contents Preface

iii

Contributors

ix

Tribute Letters

xiii

1. Insect Antifeeding Limonoids from the Chinaberry Tree Melia azedarach Linn. and Related Compounds Munehiro Nakatani

1

2. Polygodial and Warburganal, Antifungal Sesquiterpene Dialdehydes and Their Synergists Isao Kubo

23

3. Marine Bromoperoxidases—Chemoenzymatic Applications Chris A. Moore and Roy K Okuda

43

4. LC-Hyphenated Techniques in the Search for New Bioactive Plant Constituents Kurt Hostettmann, Maryse Hostettmann, Sylvain Rodriguez, and Jean-Luc Wolfender

65

5. Determination of the Absolute Configuration of Biologically Active Compounds by the Modified Mosher's Method Takenori Kusumi and Ikuko I. Ohtani

103

6. Circular Dichroism Spectroscopy and the Absolute Stereochemistry of Biologically Active Compounds Nobuyuki Harada

139

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7. Recent Applications of Circular Dichroism to Carbohydrate Conformational Analysis and Direct Determination of Drug Levels Jesús Trujillo Vázquez

191

8. Furan-Terminated Cationic π-Cyclizations in the Synthesis of Natural Products Steven P. Tanis

221

9. Chemistry and Biology of Semisynthetic Avermectins Timothy A. Blizzard

257

10. Chemical and Biological Approaches to Molecular Diversity: Applications to Drug Discovery Harold V. Meyers

271

11. Imidazoline Receptors and Their Endogenous Ligands Colin J. Barrow And Ian F. Musgrave

289

12. Oxidoredox Suppression of Fungal Infections by Novel Pharmacophores Valeria Balogh-Nair

311

13. A Mechanistic Analysis of C—–O Bond Cleavage Events with a Comparison to 3,6-Dideoxysugar Formation David A. Johnson and Hung-Wen Liu

351

14. The Molecular Mechanism of Amyloidosis in Alzheimer's Disease Michael G. Zagorski

397

15. Bacteriorhodopsin Structure/Function Studies: Use of the Demethyl Retinal Analogues for Probing of the Arg82Ala Mutant Rosalie K Crouch, Donald R. Menick, Yan Feng, Rajni Govindjee, And Thomas G. Ebrey

431

16. Autonomous Genomes David G. Lynn

445

17. Stereochemical Considerations of Immunoglobulin Heavy Chain Enhancer Activation Barbara S. Nikolajczyk And Ranjan Sen

461

Index

473

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Contributors Valeria Balogh-Nair Department of Chemistry, The City College of the City University, New York, New York Colin J. Barrow School of Chemistry, The University of Melbourne, Parkville, Victoria, Australia Timothy A. Blizzard Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey Rosalie K. Crouch Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina Thomas G. Ebrey School of Cellular and Molecular Biology, University of Illinois at UrbanaChampaign, Urbana, Illinois Yan Feng Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina Rajni Govindjee Center for Biophysics and Computational Biology and Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Nobuyuki Harada Institute for Chemical Reaction Science, Tohoku University, Sendai, Japan Kurt Hostettmann Institut de Pharmacognosie et Phytochimie, Université de Lausanne, Lausanne, Switzerland Maryse Hostettmann Institut de Pharmacognosie et Phytochimie, Université de Lausanne, Lausanne, Switzerland David A. Johnson Department of Chemistry, University of Minnesota, Minneapolis, Minnesota Isao Kubo Department of Environmental Science, Policy, and Management, University of California, Berkeley, California Takenori Kusumi Faculty of Pharmaceutical Sciences, Tokushima University, Tokushima, Japan Hung-wen Liu Department of Chemistry, University of Minnesota, Minneapolis, Minnesota David G. Lynn Department of Chemistry, The University of Chicago, Chicago, Illinois Donald R. Menick Departments of Medicine, and Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina Harold V. Meyers Chemistry and Drug Discovery Group, New Chemical Entities, Inc., Framingham, Massachusetts Chris A. Moore Department of Chemistry, San José State University, San José, California Ian F. Musgrave Prince Henry's Institute for Medical Research, Clayton, Victoria, Australia Munehiro Nakatani Department of Chemistry and Bioscience, Kagoshima University, Kagoshima, Japan Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Barbara S. Nikolajczyk* Brandeis University, Waltham, Massachusetts Ikuko I. Ohtani Department of Chemistry, Biology, and Marine Science, University of the Ryukyus, Okinawa, Japan Roy K. Okuda Department of Chemistry, San José State University, San José, California Sylvain Rodriguez Institut de Pharmacognosie et Phytochimie, Université de Lausanne, Lausanne, Switzerland Ranjan Sen Rosenstiel Research Center and Department of Biology, Brandeis University, Waltham, Massachusetts Steven P. Tanis Medicinal Chemistry I, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan Jesús Trujillo Vázquez Instituto Universitario de Bio-Orgánica ''Antonio González," Universidad de La Laguna, Tenerife, Spain Jean-Luc Wolfender Institut de Pharmacognosie et Phytochimie, Université de Lausanne, Lausanne, Switzerland Michael G. Zagorski Department of Chemistry, Case Western Reserve University, Cleveland, Ohio * Current affiliation: Immunobiology Unit, Departments of Medicine and Microbiology, Boston University Medical School, Boston, Massachusetts. Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Tribute Letters March 16, 1998 Dear Koji, On the occasion of your 70th birthday, many of your old friends and colleagues came to Columbia for a wonderful celebration in 1995. Now we are assembling a permanent record of our appreciation for your friendship and as a tribute to your many elegant and important contributions to the chemistry and biology of natural products. I can remember our first meeting, 34 years ago, in Tokyo, at the Presymposium to the IUPAC meeting in Kyoto. In the next two weeks you were our host almost every evening and introduced us to Japanese food and customs. It was a great awakening to the realization that Japanese chemistry was rapidly gaining tremendous momentum and a turning point in my career. Since that meeting I have had the pleasure and privilege of working with 26 Japanese colleagues (several of whom came from your lab). It was a pleasure to repay a little of your hospitality when you visited our homes in Sussex, New Haven and College Station, and you know that you and your wife are always welcome in Texas. You are a true pioneer in solving different problems at the chemistry–biology interface using every possible technique on vanishingly small amounts of material and your work continues to be an inspiration to all of us. Most importantly your personal qualities have ensured a permanent legacy in your many students who have done so well in our profession. It must make you feel very Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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proud to have had so many loyal and dedicated coworkers. Above all (and almost uniquely in our field) you have remained a gentleman, with the highest ethical standards in dealing with your colleagues. I don't know how you manage to work so hard yet still find time for your magic and your friends. I can guess the secret of your success in chemistry and life—that you are fortunate like myself, to have such a long and happy marriage. Betty joins with me in wishing you and your wife continued health, happiness and success for many more birthdays to come. As always! Yours very sincerely,

A. I Scott, F.R.S. Davidson Professor of Science Director of Center for Biological NMR Texas A&M University, College Station, Texas March 8, 1998 Dear Koji, "They" never stop celebrating you! "They," of course, are those who have had the privilege to obtain from you, as post-docs or as Ph.D. students, part of their life baggage. They have been also kind enough to associate to them some of your long time friends, and it was indeed a great pleasure to have the opportunity to pay tribute to you in Columbia nearly half a century after we had first met in the basement of Converse Laboratory, at Harvard, in Louis Fieser's group. When I was invited to contribute to this volume with a letter, I tried to call back the oldest memories of our meetings I could muster. For some odd reason, even though I am neither a gourmet nor a gourmand, they were nearly all memories of food. The experience of learning from you (and from Huang Wey Yuan) to use chopsticks (a very useful lesson), the dinners of frog1 or lamb2 legs in 1

My wife was working at Harvard Medical School in Pharmacology with Fieser's friend Prof. O. Krayer, on the action of the Veratrum alkaloids on frog heart. A frog: one heart, two legs. We always had a few dozen frozen legs aside for our friends. These legs, and frozen guinea pigs (one heart, one guinea pig), helped us survive on our starvation scholarships. 2

On affluent months, for a change from frogs and guinea pigs, I was buying lamb by the half at the Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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the stable-boy's rooms of the mock-French castle I was living in with Paula in Brookline.3 Food apart, another very old memory I can retrieve is that of the innumerable small sealed tubes in which you were desperately heating pristimerin with something (was it zinc or selenium?), to find its structure. Food and pristimerin apart, I also revive with a little nostalgy our outing to White Mountains, to a mountain the name of which escapes me, when we had to climb very large oblique stone slabs and you lost grip at the top, to slide down slowly at first, then quickly, on your fingers and stomach, to arrive at the bottom half skinned. But, food and pristimerin and outing apart, it is also then that I first became one of your favorite stooges, always ready to serve on any available stage, many, many times later, as afaire-valoir to your other profession. A simpleton glad to oblige. Koji, I have only one regret: that I could never find a pretext to share some (serious) work with you, in Japan, in Nairobi or in New York, even though we have both always held the same conviction that chemistry and biology share more than one border and that to follow fashion is silly when there is so much else to explore. Merci, Koji, pour ton amitié

Professor Guy Ourisson Vice President de l'Académie des Sciences Strasbourg, France Italian market. The subway passengers had to sit next to a very un-American young man carrying half a lamb protruding from his rucksack. 3

We were living in the small rooms above the stables built by a former U.S. Ambassador to Italy and to Japan, in the middle of the huge estate he had bequeathed to the township of Brookline, Lars Andersen Park. The stables were in the form of the Chateau de Chambord, or nearly so, and were the seat of the Veteran Motor Cars Association of America, the "vie de chateau," which we shared with some 100 old cars. Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Index A Abamectin (see Avermectin B1) Abequose, 378 Abscisterol A, absolute stereochemistry from modified Mosher's method, 112 Absolute stereochemistry, determination of, 139-187, 201-202 Acetaminophen, 208 Acetic acid, 1-methoxy-1-phenyl-1-trifluoromethyl-(Mosher's acid, MTPA), 104 esters, preparation of, 107 chloride, 107 Acetylsalicyclic acid, 208 Acidaminococcus fermentans, (R)-2-hydroxylglutaryl-CoA dehydratase from, 367 Aconitase, 359-361, 369, 384 cis-Aconitate, 359, 361 Adenodoxin, 380 Adenosylcobalamin (AdoCbl), 372, 373, 374, 375, 377 S-Adenosylmethionine (AdoMet), 377, 385 Adocia sp. adociaquinone A, 152, 169 adociaquinone B, 152, 169 African armyworm (see Spodoptera exempta) Agrobacterium tumefaciens, 451-453 crown gall tumor and, 451 gene transfer events in, 452 infection process of, 451 Ti plasmid and, 451-452 Algae, marine, as sources of bromoperoxidases, 45-46

brown (Ascophyllum nodosum), 45-46 green, 46 red, 46 Allylic oxidation, 164, 165, 231, 232 Alprazolam, 208 Alzheimer's disease (AD), 397-424 amyloid β-peptide of, 399 AM1, 140 Amides, 339 macrocyclic, 339 antifungal activity, 341-344 biological activity, 340-341 metallomacrocyclic, 339 Amidopyrine, 208 Amines macrocyclic, 327-328 synthesis of, 336-340 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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[Amines] oxidation of, 328 peroxynitrite, 328 peroxynitrous acid, 328 Amino acids, catabolism of, 352 Amino acid esters, modified Mosher's method applied to, 126-127 Amino alcohols, modified Mosher's method applied to, 126-127 γ-Aminobutyrate, metabolism of, 369 Amoxicillin, 208, 209 Amphotericin B, 312 Ampicillin, 208, 209, 211, 212, 215 Amylin (see also Amyloidosis) amyloid deposits, 397 conversion of, 398 cotinine and, 414 formation of, 398 nicotine and, 414-420 β-amyloid inhibitors, 410-411 hexadecyl-N-methylpiperidinium bromide (HMP), 410-411 myristyltrimethylammonium (MTMA), 411 N-tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (3-14), 411 β-peptides, 397, 398 amino acid sequence of, 398 "amyloid-initiated cascade," 420 binding with heparan sulfate proteoglycans, 422 circular dichroism (CD) studies, 402-405, 410 effect of micelles, 404, 411-412 isodichroic points, 404 poly-L-lysine curves, 404

formation of, 398 Fourier transform infrared (FTIR) microspectroscopy, 423 mechanism of accumulation of, 420 nicotine-peptide complex, 416-417, 419 3D model of, 418-419 NMR studies, 405-413 chemical shift, 412, 415 NH temperature coefficients, 408-409, 412 nicotine, 415 Nuclear Overhauser effect (NOE), 407-408, 411, 412, 415 2D NOESY spectrum, 411 presenilins, 399 solution conditions, 401-413 solution conformations, 400 structures, 409 α-helix, 398, 400, 403, 404, 406-409, 412 random coil, 400, 406-407 secondary, 403, 406-407 β-sheet, 398, 400, 403, 408, 409, 412 NH-NH connectivity, 413 2D NOESY spectrum, 411 β-turn, 400 Amyloidosis, 397 424 Alzheimer's disease, 397 definition, 397 molecular mechanism of, 397 ANOVA, 203, 211 Antifungal sesquiterpene dialdehydes (see Sesquiterpene dialdehydes) Antifungals, 311-346 (see also Candida albicans, Cryptococcus neoformans, Swertia calycina)

azoles, 313 oxidoredox suppression, 311-312, 331, 337, 339, 341-344 polyene antifungals, 313 Anxiety, 76 Aperitif Suze (see Gentiana lutea) Aphidicolin, 230 synthesis of, 231-234 Aragupetrosine A, 109, 110, 116 Aragusterol A, absolute stereochemistry from modified Mosher's method, 111 Araucaria cookii, 173 Araucaria cunninghamii, 173 Ascarylose, 352, 378 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Astemizole, 208 Atropisomer, 140 Autonomous genome (see Genome) Avermectins, 257 biology of, 265-268 fragmentations and rearrangements of, 260-262 modified glycosides of, 262-263 stereoisomers of, 263-265 Avermectin B1, 257, 267 1',13-bis-epi-, 263, 267 disaccharide excision from, 262, 263 2-epi-, 267 13-epi-, 263, 265, 267 19-epi-, 264-265, 267 3,4-epoxide, 259-260, 267 8,9-epoxide, 258-260, 267 fragmentation of, 261 7-O-trimethylsilyl-, 267 Avermectin B2, 261, 262 13-epi-, 261, 262 Azedarachin, 2, 4 2'-Azido-2'deoxyuridine 5'-phosphate, 376 Azulene, (8aR)-1,8a-dihydro-, 143-146 calculated CD spectrum of, 145-146 molecular modeling of, 144-145 (+)-1,8a-dihydro-3,8-dimethyl-, 139, 145-150 CD and UV spectra of, 144 (+)-1,8a-dihydro-3, 8a-dimethyl-, 143, 149-150

synthesis of, 149-150 (1S, 8aR)-(+)-1, 8a-dihydro-1-methoxy-6, 8a-dimethyl-, 143, 147-148 synthesis of, 147-148 (1S, 8aR)-(+)-1, 8a-dihydro-1-methoxy-8a-methyl-, 143, 147-148 CD and UV spectra of, 150 synthesis of, 147-148 (1S, 8aR)-( + )-1, 8a-dihydro-8a-methyl-, 143, 148-151 CD and UV spectra of, 151 synthesis of, 148-150 1,4-dimethyl-, 139, 142, 143 (8S, 8aS)-(–)-3,8-dimethyl-1,2,6,7,8,8a-hexahydro-, 143 Azulen-6-one (1S, 3aR, 4S, 7R, 8aS)-(+)-decahydro-7-bromo-1,4-dimethoxy-8a-methyl-ketal, synthesis of 147-148 x-ray structure of, 149 B B cells (see Immunoglobulin) Bacillis subtilis, fumarate hydratase in, 361 genomic sequence of, 445 sesquiterpene dialdehyde effect on, 24, 25 Bacteriorhodopsin (bR), 431 photocycle of, 432 Bacterium host range competence, 453 Baeyer-Villiger-type oxidation, 2 Banisteriopsis caapi (tropical liana), 76 Bellidifolin (see Xanthone,1,5,8-trihydroxy-3-methoxy-) Bengazole A, absolute stereochemistry from modified Mosher's method, 110, 116 Benzene,2,3-dimethyl-1,4-dimethoxy-, 166 Benzocyclobutene, 3, 6 -dimethoxy, 162, 163, 166

Biflavone, 140 Biopanning, 273 Biphenyl-2,2'(-diol, (+)-3,3'-diaectyl-4,4',6,6'-tetramethyl enantioresolution of, 183-184 synthesis of, 181-183 Bis(trimethylsilyl)trifluoroacetamide (BSTFA), persilylation with, 259, 261, 266 Blanesin, absolute stereochemistry from modified Mosher's method, 113 Blasticidin S, 384 Brine shrimp assay, 266-267 applied to avermectins, 267 Bromoperoxidases, marine, 43-64 activity, 49, 51 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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[Bromoperoxidases, marine] algae as source, 45-46 application, 62 bromide concentration, 51 bromohydrin, 52 bromoperoxidase, 51 buffer, 51 Caldariomyces fumago, 44 chloroperoxidases and, 43, 44 enzyme activity of, 50-51 haloperoxidases and, 43, 44 assay for activity of, 49 from Caldariomycesfumago, 44 hydrogen peroxide and, 49-50 immobilization, 51, 60 iodoperoxidases and, 44 marine invertebrates as sources, 45-46 mechanism of action, 47-48 organic synthesis, 62 pH, 49, 50 radiolabeling with, 62 reaction products, 52-54, 56 structures, 47 C Caldariomyces fumago, 44 Calypogeia granulata, 143 (1S)-(–)-Camphanic acid chloride, 183 Candida albicans, 93 oxidoredox suppression of, 311-312, 328, 331, 337, 339, 341-344

sesquiterpene dialdehydes effect on, 23, 24 Canellaceae family, 24 Canscora decussata, 76 Carbodiimide, 1-ethyl-3-(3-dimethyl-aminopropyl)- (EDC), 107 Carbohydrates conformational analysis of, 193-202 by circular dichroism, 194-202 by 1H NMR, 195-202 Carbon dioxide, hydration of, 356-357 Carbonic anhydrase, 356-357, 384 Carquinostatin, absolute stereochemistry from modified Mosher's method, 111 (+)-Carveol, 125 Cefactor, 204, 205 Cefadroxil, 204-207 Cefamandole, 204-206 Cefapirin, 204-206 Cefoperazone, 204, 205 Cefotaxime, 204, 205 Cefoxitin, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215 Cefsulodin, 204, 205 Ceftriaxone, 204-206, 217 Cefuroxime, 204, 205 Celeromycalin, absolute stereochemistry from modified Mosher's method, 115 Cepaciamide A, absolute stereochemistry from modified Mosher's method, 110, 114 Cephalexin, 204, 205, 208, 209, 211, 212, 215, 217 Cephalosporins, analysis of by circular dichrosim, 203-217 Cephalosporium aphidacola, 230 Cephalotin, 204, 205, 217 Cephazolin, 204, 205

Cephradine, 204, 205 Chemotaxonomy, 67 Chinaberry tree (see Melia azedarach Linn.) Chiral anisotropic reagents, 104, 128-130 Chironia krebsii, 77 LC/TSP-MS analysis of, 79-84 LC/UV analysis of, 79-84 LC/UV/MS analysis of, 79-84 MAO-A inhibition by, 79 secoiridoids of, 79-84 xanthones of 79-84 Chloramphenicol, (R)-2-hydroxylglutaryl-CoA dehydratase inhibition by, 367 1-Chloro-3-cyano-2-methylpropene, 435 Chloroperoxidase, 44 Chorismate, 371 Chorismate synthase, 371-372, 383 Chromodoris maridadilus, 247 Chromomycin A3, 154 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Ciprofloxzcin, 208 Circular dichroism spectroscopy, 139-187, 191-217 Citrate, 359, 360 Citrate (isocitrate) hydrolase, 359 Citric acid cycle (see Krebs cycle) Cladosporium cucumerinum, 93 Clavukerin A, 118, 143, 146 Clavekerin B, 143 Clorgyline, 76, 77 Clostridium, hydroxy acyl-CoA dehydratases from, 367 Clostridium butyricum, 4-hydroxybutyryl-CoA from, 369 Clostridium propionicum (R)-lactyl-CoA dehydratase from, 367 L

-serine hydratase from, 364

Colitose, 378 Combinatorial chemistry, 272 mixture synthesis, 278 multiple simultaneous synthesis (parallel, discrete, array synthesis), 278-283 pin technology, 278-279 solution phase, 279 spatially addressable, light directed synthesis, 279 split synthesis (split-pool, split-mix, portion mixing), 275-278 encoding strategies, 277-278 tea bag method, 279 Combinatorial libraries, 272 epitope libraries, 273 phage libraries, 272-274 universal library, 280-281 Configurational interactions (CIs), 141

Conicasterol, absolute stereochemistry from modified Mosher's method, 111 Cotrimoxazole, 208 Cotinine, 414 Cotton effect, 192 Creatinine, 216 Crenulacetal B, absolute stereochemistry from modified Mosher's method, 108, 109 Crotonase (see Enoyl-coenzyme A hydratase) Crotonyl-CoA, 369, 370 Crown gall tumor, 451 Cryptococcus neoformans oxidoredox suppression of, 311-312, 331, 337, 339, 341-344 Cryptophycin A, absolute stereochemistry from modified Mosher's method, 110, 112 Cupressuflavone, (aR)-(+)-4',4''',5,5",7,7"-hexa-O-methyl, 185 (–)-4',4",7,7"-tetra-O-methyl, 140, 173-187 CD and UV spectra of, 174-175, 181, 186 synthesis of, 181-186 Cyclohexanecarboxylic acid, 4-methyl-, chiral anisotropic reagents applied to, 130-132 Cyclohexene,2,6,6-trimethyl-1-vinyl, Diels-Alder reaction of, with dimethyl acetylenedicarboxylate, 221, 222 2-Cyclopentenone, 4-hydroxy-2-methyl-, resolution of, 242 2-Cyclopentenone, 4-methoxy-2-methyl-, 239, 240, 243 Cyclopropanecarboxylic acid, 2, 2-dimethyl-3-(2, 2-dichlorovinyl), chiral anisotropic reagents applied to, 132, 133 Cytidine diphosphate-ascarylose, 378, 379 Cytidine diphosphate-6-deoxy-L-threo-D-glycero-4-hexulose, 352, 379 Cytidine diphosphate-6-deoxy-∆3, 4-glucoseen reductase, 352 Cytidine diphosphate-6-deoxy-L-threo-D-glycero-4-hexulose-3 -dehydrase, 351, 352, 379, 380-381, 382, 383, 384, 385 Cytidine diphosphate-6-deoxy-L-threo-D-glycero-4-hexulose-3 -dehydrase reductase, 380-382, 383, 384, 385

Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Cytidine diphosphate-3, 6-dideoxy-D-glycero-D-glycero-4-hexulose, 379 Cytidine diphosphate-3, 6-dideoxy-D-glycero-D-glycero-4-hexulose-5-epimerase, 379 Cytidine diphosphate-3, 6-dideoxy-D-glycero-L-glycero-4-hexulose-4-reductase, 379 Cytidine diphosphate-a-D-glucose, 379 Cytidine diphosphate-D-glucose-4, 6-dehydratase, 365, 379 Cytidine triphosphate, coupling with a-D-glucose-1-phosphate, 378, 379 D (E)-2-Decenoyl-ACP, 354 (Z)-3-Decenoyl-ACP, 354 3-Dehydroquinase, 355-356 3-Dehydroquinate synthase, 357 3-Dehydroquinic acid, 355 3-Dehydroshikimic acid, 355 (-)-Dendrobine, application of modified Mosher's method during the synthesis of, 125, 126 Dendrolasin, 7, 8-epoxy, 230, 231 Denticulatolide, absolute stereochemistry from modified Mosher's method, 108, 109 2'-Deoxy-2'-mercaptouridine 5'-diphosphate, inactivation of ribonucleotide reductase by, 375, 376 Deoxyribonucleic acid, biosynthesis of, 375 2-Deoxy-scyllo-inosose synthase, 367 Depression, 76 Desacetylaltohyrtin, absolute stereochemistry from modified Mosher's method, 111 Desmethylbellidifolin (see Xanthone, 1, 3, 5, 8-tetrahydroxy-) Diaphorase, 380 Diclofenac, 208 Dicot defense pathway, 449 Dicotyledonous plant, 449 Diethyl (3-cyano-2-methylprop-2-enyl)-phosphonate, 435 Dihydroxy-acid dehydratase, 362-363 Diol dehydrase, 351, 372-374

Dipole strength (Dba), 141 Dipole velocity method, 141 Directed evolution, 274 Dithiothreitol, 376 DNA polymerase a, 231 Dolabelide A, absolute stereochemistry from modified Mosher's method, 115 Dysedea fragilis, 247 E Edman degradation, in split synthesis, encoding strategies, 277 Ehrlich's reagent, 7 Enolase, 357-359, 384 Enolpyruvateshikimate-3-phosphate (EPSP), 371 Enoyl-coenzyme A hydratase, 351, 352-353 Enshuol, absolute stereochemistry from modified Mosher's method, 110, 114 Epifagus virginiana, 447 Epitope libraries (see Combinatorial libraries) Escherichia coli 3-dehydroquinase from, 355 dihydroxy-acid dehydratase from, 362 fatty acid metabolism in, 353 fumarase A from, 361 fumarase B from, 361 genomic sequencing of, 445 β-hydroxydecanoylthioester dehydrase from, 354 ribonucleotide reductase from, 375, 376, 377 sesquiterpene dialdehyde effect on, 24 site-directed mutagenesis in, 435, 436 thymidine diphosphate-D-glucose 4, 5-dehydratase from, 365 Ethanolamine ammonia lyase, 373

Euglena gracilis, fumarate hydratase from, 361 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Europium tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorate [Eu(hfpc)3], 231 Europium tris[3-(trifluoromethylhydroxymethylene)-(+)-camphorate [Eu(tfc)3], 184 Eurylene, absolute stereochemistry from modified Mosher's method, 110 EXAFS, studies of carbonic anhydrase, 357 Exciton chirality method, 192 applied to halenaquinols, 153-155 Exciton coupling in (–)-4', 4", 7, 7"-tetra-O-methyl-cupressuflavone, 175 in naphthalene-diene systems 156-159 of twisted π-electron systems 156-159 Exo-anomeric effect, 193, 196, 199, 200 F Fastigilin C, synthesis of, 237-243 Fatty acids biosynthesis, 354 metabolism, 352, 353 synthase, in rats, 354 Ferredoxin-NADP+ reductase (FNR), 381, 383 Ferricytochrome c, 330 Ferrihemes, 330 Flavin adenine dinucleotide (FAD/ FADH), 369, 370, 381, 382, 383, 386 Flavin, 367, 372 mononucleotide (FMN), 367, 368 monooxygenase, 323 Flavodoxin, 377 Flavodoxin reductase, 377 Flavones, 80 Fluconazole, 312

(6R)-6-Fluoro-5-enolpyruvylshikimate-3-phosphate, inhibition of chorismate synthase by, 372 (E)-2'-Fluoromethylene-2'-deoxycytidine 5'-phosphate, inactivation of ribonucleotide reductase by, 376 (Z)-2'-Fluoromethylene-2'-deoxycytidine 5'-phosphate, inactivation of ribonucleotide reductase by, 376 Fourier transform infrared (FTIR) microspectroscopy, 423 Friedelan-3β-ol, modified Mosher's method applied to, 120 Fukurinolal (see Hydroxyacetyldictyolal) Fumarate hydratase (fumarase), 361 Fumonisin B1, absolute stereochemistry from modified Mosher's method, 113, 126 Fungal infections, oxidoredox suppression of, 311-346 Furan cationic-cyclizations terminated by, 224 N-acyliminium ion initiated, 248-250 acylium ion initiated, 237-240 allylic alcohol initiated, 236-237, 243-246 enone intiated, 243-248 epoxide initiated, 224 230 in the synthesis of aphidicolin, 230-234 in the synthesis of pallescensin A, 230-231 in the synthesis of warburganal, 223 functional equivalents, 223 3-Furylmethylmagnesium chloride coupling reactions of, 225-226, 230, 231, 232, 233, 247, 248 preparation of, 225 Fusobacterium nucleatum, (R)-2-hydroxylglutaryl-CoA dehydratase from, 367 G Galactonate dehydratase, 359 α-D-Galactopyranosides, 197 Garcinia mangostana, 140, 173

Gedunin, 2 Genome angiosperm evolution, 448 autonomous, 445-460 altered backbone product, 455 definition, 446, 456 DNA information, 455 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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[Genome] construction/reduction analysis, 450 bottom-up, 446, 451-454 octopine in, 452 opine production, 453 reductive amination, 452 Ti plasmid, 451-453 tra regulon, 452 virulence regulon, 452 top-down, 446-447 haustorium, 447-450 host defenses, 447 host specialization, 447 obligate parasite, 447 extrachromosomal, 451-453 function, 446 octopine, 452 parasite genome, 450 parasite strategy, 448 reductive amination, 452 replication process, 456 template turnover, 454 tra regulon, 452 Gentiana lactea, 77 Gentiana lutea, 77-79 LC/TSP-MS analysis of, 77-78 LC/UV analysis of, 77-78 LC/UV/MS analysis of, 77-78

Gentiana rhodantha, 84-86 LC/TSP-MS analysis of, 84-86 LC/UV analysis of, 84 LC/UV/MS analysis of, 84-86 secoiridoids of, 80 xanthones of, 80 Gentamycin, 208 Gentianaceae as source of antidepressive agents, 75-76 Gentisin (see Xanthone, 1, 7-dihydroxy-3-methoxy-) Geraniol, 231, 232 Geranyl chloride, 6, 7 -epoxy-, 230, 231 Gibberellic acid, chiral anisotropic reagents applied to, 132, 133 β-D-Glucopyranosides: absolute configuration assignment of, 201-202 2, 3-bis-O-(p-bromobenzoyl)-4, 6-bis-O-(p-methoxycinnamates), CD spectra of, 194, 195 gg-rotamers of, 195, 197 gt-rotamers of, 195, 196 2, 3, 4, 6-tetrakis-O-(benzoates), 197, 198 of (–)-borneol, 200 of (+)-borneol, 200 of cholestanol, 200 of cholesterol, 200 of dimethyl D-malate, 200, 202 of dimethyl L-malate, 200, 202 of (–)-menthol, 200 of (+)-menthol, 200 of (–)-methyl 3-hydroxybutyrate, 200

of (+)-methyl 3-hydroxybutyrate, 200 of (–)-neomenthol, 200 of (+)-neomenthol, 200 of (–)-octanol, 200 of (+)-octanol, 200 of testosterone, 200 2, 3, 4, 6-tetrakis-O-(p-bromobenzoates), 197, 198, 201 acetyl, 198 (–)-bornyl, 198 (+)-bornyl, 198 (–)-menthyl, 198 (+)-menthyl, 198 methyl, 198 (–)-octyl, 198 (+)-octyl, 198 β-L-Glucopyranosides, 201 2, 3, 4, 6-tetrakis-O-(benzoates), 197, 198, 201, 202 of cholestanol, 200, 201 of cholesterol, 200, 201 of testosterone, 200 α-D-Glucose-l-phosphate, coupling with CTP, 378, 379 α-D-Glucose-l-phosphate cytidylyltransferase, 378, 379 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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(E)-Glutaconyl-CoA, 367, 368 L-Glutamic acid dimethyl ester, modified Mosher's method applied to, 127 Glutaredoxin, 376 Glutaredoxin reductase, 383 Glycerol dehydrases, 372 Glycerol, fermentation of, 372 Glycerol phosphate dehydratase, 359 Glycoconjugates, 193 Glycoprotein, 193 Goniocin, absolute stereochemistry from modified Mosher's method, 112 H Halenaquinol, 152-168, 171 absolute stereochemistry of, 153-161 CD spectrum of, 156 dimethyl ether, 154-155, 163, 167 CD spectrum of, 168-169 synthesis of, 162-168 Halenaquinol sulfate, 152, 161 Halenaquinone, 151 168, 171 absolute stereochemistry of, 153-161 synthesis of, 161-168, 170-171 Halenia corniculata, 86-87 glycosides of, 80, 87 LC/ES-MS analysis of, 86-88 LC/TSP-MS analysis of, 86-88 Halobacterium salinarium, 431, 434 Halogenated marine natural products, 47 Haloperoxidases, 44 heme ("H" haloperoxidases), 44

nonheme ("NH" haloperoxidases), 44 Hapalosin, absolute stereochemistry from modified Mosher's method, 110, 113 Heparan sulfate proteoglycan binding in Alzheimer's Disease, 422 Hexopyranose gg-rotamers of, 193 gt-rotamers of, 193 High-throughput screening, 271 Horner-Emmons olefination, 437, 438 Host defense peptide, 317 Huntington's chorea, 76 Hydrogen peroxide, 49-50, 448, 449 Hydroxyacetyldictyolal (fukurinolal), absolute stereochemistry from modified Mosher's method, 108, 109 (R)-2-Hydroxybutyryl-CoA, 369 4-Hydroxybutyryl-CoA, 369, 370 4-Hydroxybutyryl-coenzyme A dehydratase, 369-371, 383 4-Hydroxycrotonyl-CoA, 369, 370 β-Hydroxydecanoyl-ACP, 354 β-Hydroxydecanoylthioester dehydrase, 354 (R)-2-Hydroxyglutaryl-CoA, dehydration of, 367, 368 (R)-2-Hydroxyglutaryl-coenzyme A dehydratase, 367-369 4-Hydroxyglutaryl-coenzyme A dehydratase, 370-371 Hydroxylamine, 321 conversion of, 321 Hydroxymethylation, Stork's reductive, 163, 164, 165 Hydroxyurea, inactivation of ribonucleotide reductase by, 375 Hypericin, 76 Hypericum perforatum (St. John's wort), 76, 77 MAO-A inhibition by, 79 Hypselodoris godeffroyana, 247

I Imidazoline receptors, 289-307 affinity and binding sites, 289-290 α1-adrenoceptors, 290 α2-adrenoceptors, 296, 301 imidazoline, 289, 296 I1-imidazoline-binding, 290 clonidine, 289-290, 300 guanabenz, 290 idazoxan, 289, 290 moxonidine, 290 naphazoline, 290 oxazoline, 289-290 rilmenidine, 290 I2-imidazoline-binding, 290 amiloride, 294 I2A-sites, 294 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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[Imidazoline receptors] I2B-sites, 294 2-(2-benzofuranyl)-2imidazoline (2-BFI), 294 cirazoline, 294 clonidine, 294 (2-4, 5-dihydroimidaz-2-ylquinoline) (BU224), 294 idazoxan, 289, 290, 294 moxonidine, 294 I3-imidazoline-binding, 290 structure/affinity relationships, 292- 293 classification of, 291 clonidine-displacing substance (CDS), 294-306 agmatine, 296-302 cardiovascular effects of, 299-300 distribution of, 298, 299 extraction of, 298, 303-304 gastrointestinal functions, 300-301 interaction of, 301 biological activity of, 296-297 brain-derived, 297 endogenous, 295, 303 inhibitor HPLC of, 305-306 purification of, 304-305 partially purified, 297 plasma-derived, 297 imidazoline preferring sites, 289 imidazoline-guanidinium receptive sites (IGRSs), 289 nonadrenergic imidazoline-binding sites (NAIDSs), 289

pharmacology and function of, 289-294 Imines imine coupling reactions, 456 macrocyclic structures of, 337 synthesis of, 337 reversible imine condensation, 454 Immunoglobulin heavy chain activation, 461-471 B cells, 461 helical alignment, 463 transcriptional activation, 463 deoxyribonucleic acid and, 465-466 ETS domain proteins, 462, 464, 465 orientation mutated enhancers, 464 heavy chain enhancer activity, 461 stereochemical considerations, 461 µ enhancer, 462, 464-471 B cell-specific activation, 465 core region, 462 DNA flexure, 465, 466-471 binding domain, 467, 468 circular permutation assay, 466, 467 directed bend, 466, 467, 471 distortion, 467 phasing analysis, 467-471 protein-induced changes, 466, 468, 470 Ets-1, 467, 469 PU.1, 466 471 TFE3, 466, 467, 469-471

µA-µB spacing, 462 mechanism, 462 mechanistic analysis, 470 mutated (F2-5), 463-465 sequences, 463 wild-type (F1), 464, 465 µ heavy chain gene (IgH), 461 transcriptional activity, 461 Inflatene, 143 Ingamine A, absolute stereochemistry from modified Mosher's method, 113 Ingenamine, absolute stereochemistry from modified Mosher's method, 113 Ingenamine E, absolute stereochemistry from modified Mosher's method, 113 Insect antifeedant, 1, 7, 9, 13, 19, 24 Isocitrate, 359 Isoclavukerin A, absolute stereochemistry from modified Mosher's method, 118 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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L-Isoleucine biosynthesis of, 362 methyl ester, modified Mosher's method applied to, 127 L-Isoleucinol, modified Mosher's method applied to, 127 Isoorientin, 80, 91, 93 from Swertia calycina, LC/MS of, 90 Isosorbide dinitrate, 208 Isovitexin, 80, 91, 93 from Swertia calycina, LC/MS of, 90 Ivermectin, 257, 267 J Jaspiferal A, absolute stereochemistry from modified Mosher's method, 114 Junicedranol, absolute stereochemistry from modified Mosher's method, 116 K 3-Ketoadociaquinone A, 152 a-Ketoglutarate, 364 Kinetic resolution, 107 Krebs cycle (citric acid cycle), 359, 361 L β-Lactam antibiotics CD analysis of, 208-217 Lactobacillus leichmannii, ribonucleotide reductase from, 375, 376 Latrunculin S, absolute stereochemistry from modified Mosher's method, 114 LC/DAD-UV (liquid chromatography-diode array detection UV), 6670 LC/MS (liquid chromatography-mass spectrometry), 66, 70-73 LC/NMR (liquid chromatography-nuclear magnetic resonance spectroscopy) 66, 73-75 LC/UV (liquid chromatography-ultraviolet spectroscopy) 66 LC/UV/MS, 74-75

L-Leucine methyl ester, modified Mosher's method applied to, 127 Leustroducin H, absolute stereochemistry from modified Mosher's method, 115 Licaria puchuri-major (Lauraceae), 32 Limonoids (C-seco, D-seco classes), 1-20 biogenesis of, 19 insect antifeedant effects of, 13, 19 isolation of, 7, 8 Melia azedarach as source, 1, 4 NMR spectra of, 9-10 structures of 6-acetoxy-3β-11α-dihydroxy-7-oxo14β, 15β-epoxymeliac-1, 5 -diene, 3 6-acetoxy-3β-hydroxy-7-oxo-14β, 15β-epoxymeliac-1, 5 -diene, 3 6-acetoxy-7α-hydroxy-3-oxo-14β, 15β-epoxymeliac-1, 5 -diene, 3 7α-acetoxy-3β-hydroxy-14β, 15β-expoxygedunan-1-ene, 4 12-O-acetylazedarachin, 4 amoorastatin, 4, 14 aphanastatin (1, 2-diacetyl analogue of trichilin B), 11 apo-euphol type, 3, 4 amoorastatone, 4, 11, 15 aphanastatin, 4, 15 azadarachins A, B, C, 1, 2, 12-16 12-hydroxyamoorastatone, 15 iso-chuanliansu, 4, 15 meliatoxins A2, B1, B2, 4, 15 sendanal, 14 trichilin B, 14, 15

azadirachtin, 2, 16 azadirone, 3, 12 azedarachins A, B, C, 4 1-cinnamoylmelianolone, 6, 7 deacetylsalannin, 5 6, 11α-diacetoxy-3β-hydroxy-7-oxo-14β, 15β-epoxymeliac-1, 5-diene, 3 gedunin, 4, 15 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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[Limonoids (C-seco, D-seco classes)] 12α-hydroxyamoorastatone, 4 meldenin, 3 meliacarpinins, 6, 12, 13, 15 nimbidinin, 6 nimbolidins A, B, 3, 5, 16 nimbolinin B, 5, 15 nimbolins A, B, 2, 3, 5, 12, 16 ohchinal, 3, 5, 15 ohchinin, 5, 15 ohchinin acetate, 5, 16 ohchinolal, 5 ohchinolides A, B, 5, 12, 15 salannin, 5, 12 spirosendan, 5, 15 1-tigloy1-3-acetoxy-11-methoxyazadirachtinin, 12 3-O-β-D-glucopyranoside, 4 toosendanin, 14 trichilins, 4, 9-11, 15-19 biogenesis and antifeedant activity, 19 from different species and reaction products, 16-17 structures, 4, 9-11 structure-activity relations in, 18 Lipase, porcine pancreatic (PPL), 242 Lipopolysaccharide (LPS), 378 Lobatriene, absolute stereochemistry from modified Mosher's method, 117-118 Lobster, enolase from, 358 Luteolin, 80, 87 7-O-glucosyl-, 80, 87

from Halenia corniculata, LC/MS of, 88 7-O-primeverosyl- (cesioside), 80, 87 2, 3-Lysine aminomutase, 385 M Macrocarpal C, absolute stereochemistry from modified Mosher's method, 110 Macrocyclic (see Amides; Amines; Imines) Manadic acid B, absolute stereochemistry from modified Mosher's method, 110, 114 Mangiferin, 80, 84 from Gentiana rhodantha, LC/MS of, 85 Maprotiline hydrochloride, 208 Marine bromoperoxidases (see Bromoper-oxidases) Mass spectrometry atmospheric pressure chemical ionization, 70 continuous flow fast atom bombardment (CF-FAB), 71, 74-75 electrospray, 70, 74-75 particle beam (PB), 70 thermospray (TSP), 70, 71 MCD assay for haloperoxidase activity, 49 Melancholia, 76 Meliaceae, family, 1 Melia azadirachta indica Juss (neem tree), 1 Melia azedarach, 3 Linn. (Chinaberry tree), 1-20 structures of limonoids from, 4, 5 Melia toosendan, 3 Meliavolin, absolute stereochemistry from modified Mosher's method, 115 (–)-Menthol, modified Mosher's method applied to, 108 Mosher's method applied to, 202

Metallomacrocycles, 328-331 synthesis of, 336-340 Methane monooxygenase, 380 Methemoglobin, 330 L-Methionine, methyl ester, modified Mosher's method applied to, 127 Methionine synthase, 372 p-Methoxybenzoyl chromophore, 175 p-Methoxycinnamoyl chromophore, 175 (S)-2-Methylbutanoic acid, chiral anisotropic reagents applied to, 130-133 Methylmalonyl coenzyme A mutase, 372-373 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Metmyoglobin binding with, 330 Metoclopramide, 208 Mirabimide E, absolute stereochemistry from modified Mosher's method, 110, 112 Mitsunobu lactonization, 264, 266 MMP2, 140 applied to (–)-4', 4", 7, 7"-tetra-O-methyl-cupressuflavone, 175-176 Modified Mosher's method, 105-107, 123-125 applications to natural products, 108-123 applications to primary amines, 125-128 applications to synthetic compounds, 123-125 Molecular mechanics, 141 Monoamine oxidase (MAO-A, -B), 76, 77, 84 inhibition by Chironia krebsii, 79 inhibition by Hypericum perforatum, 79 inhibition by xanthones, 77-79 Monocot cell surfaces, 449 MOPAC 93, AM1, 140 applied to (8aR)-1, 8a-dihydroazulene, 145 applied to naphthalene-diene systems, 159 Mosher's acid, MTPA (see Acetic acid, 1-methoxy-1-phenyl-1-trifluoromethyl-) Mosher's method, 104-105 Moxalactam, 204, 205 Moxonidine, 290 MTPA plane (Mosher's plane), 105, 106 Mucocin, absolute stereochemistry from modified Mosher's method, 114 Murihexocin A, absolute stereochemistry from modified Mosher's method, 116 Mycaperoxides A, B, absolute stereochemistry from modified Mosher's method, 110, 111 Myeloperoxidase, 316

N NADH oxidase, 381 Nakafuran 9, 247 synthesis of, 247-248 1, 4-Naphthoquinone, 2-methoxy, 93, 94, 95, 96, 97 from Swertia calycina, LC/NMR of, 93, 94 from Swertia calycina, LC/UV of, 94 Neem tree (see Melia azadirachta indica Juss) Netilmycin, 208 Neutrophils, 315-316 taurine conversion in, 316 Nicotiana tabacum, 447 Nicotinamide adenine dinucleotide (NADH/NAD+), 352, 365, 366, 367, 378, 380, 381, 382, 383, 386 Nicotinamide adenine dinucleotide phosphate (NADPH/NADP+), 366, 371, 377 Nicotine, 414-420 Nifedipine, 208 Nitric oxide (NO) effector molecule function, 313 ferricytochrome c binding with, 330 ferriheme reaction with, 330 nitric oxide synthase, inducible, 314 metallomacrocycles and, 329-331 methemoglobin reaction with, 330 metmyoglobin binding with, 330 nitrosohemoglobin, 330 peroxynitrite, 314, 328 superoxide anion, 314 Nitrobenzoate, (R)-2-hydroxylglutaryl-CoA dehydratase inhibition by, 367 Nitroglycerin, 208

Nitrones (see also Oxaziridines; VBN-3; VBN-4), 320, 324-327 hydroxylamine and, 321 synthesis of, 335-336 2-Nitrophenol, (R)-2-hydroxylglutaryl-CoA dehydratase inhibition by, 367 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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3-Nitrophenol, (R)-2-hydroxylglutaryl-CoA dehydratase inhibition by, 367 4-Nitrophenol, (R)-2-hydroxylglutarylCoA dehydratase inhibition by, 367 Nitrosohemoglobin, 330 Noradrenaline, 76 Norfloxacin, 208 Nucleotidyl diphospho 4, 6-dehydratase, 365 Nystatin, 312 O Octopine, 452 Ohchinal, 3 Onchocerciasis, 257 Oxaziridines, 322-324 macrobicyclic (see also VBN-2) biological activity of, 335 energy-minimizing conformation, 333 synthesis of, 334 sulfonyloxaziridines, 319-323 N-oxides and, 320, 323, 325 nitrones and (see also Nitrones), 320-321, 324-326 synthesis of, 332 Oxidation, Baeyer-Villiger-type, 2 Oxidoredox suppression of fungal infections, 311-345 Oxidosqualenes, absolute stereochemistry from modified Mosher's method, 110, 116 Oxygen transfer agents, 324 P Palauolol, absolute stereochemistry from modified Mosher's method, 116 Pallescensin A, 230 3β-hydroxy, 230, 231

synthesis of, 230-231 Pamamycins, absolute stereochemistry from modified Mosher's method, 110 Parallel synthesis (see Combinatorial synthesis, Multiple simultaneous synthesis) Paratose, 378 Pargyline, 77 Parkinson's disease, 76 Pateamine A, absolute stereochemistry from modified Mosher's method, 110, 115 Penicillium chrysagenum sesquiterpene dialdehyde effect on, 24 Pentanoic acid, (S)-2-methyl-, chiral anisotropic reagents applied to, 132, 133 Pent-4-enoic acid, (S)-2-methyl, chiral anisotropic reagents applied to, 132, 133 Peptostreptococcus asaccharolyticus, L-serine dehydratase from, 363, 364 Peroxidases, apoplastic, 448 Peroxide shunt, 321 Perhydrohistrionicotoxin, 249, 250 Petrosynol, 111 Pfitzner Moffat oxidation, 170 Phage libraries (see Combinatorial libraries) L-Phenylalanine methyl ester, modified Mosher's method applied to, 127 L-Phenylalaninol, modified Mosher's method applied to, 127 Phenylglycinamide, N,N-dimethyl-(PGDA), 104 as a chiral anisotropic reagent 128-133 preparation of, 130 Phenylglycine, methyl ester (PGME), 104 as a chiral anisotropic reagent 128-133 preparation of, 130 Phenylpropanoids, 32 anethole, 32, 35 eugenol, 32 methyleugenol, 32

safrole, 32 Phloroacetophenone, 181 Phomactin B, absolute stereochemistry from modified Mosher's method, 112 2-Phospho-D-glycerate (2-PGA), 357, 358 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Phosphoglycolate, 358 Phosphonoacetohydroxamate (PhAH), 358 Photodiode arrary detection, coupled with liquid chromatography, 67-70 π-Electron self-consistent field/configuration interaction/dipole velocity molecular orbital method (SCF-CI-DV MO), 139-142 applied to (8aR)-1, 8a-dihydroazulene, 145-146 applied to halenaquinol dimethyl ether, 155-156 applied to naphthalene-diene systems, 159-162 applied to (–)-4', 4'', 7, 7"-tetra-O-methyl-cupressuflavone, 175-180 Pimpinella anisum (Umbelliferae), 32 Pipemidic acid, 208 Plasmid genes, 447 Pneumocystis carinii oxidoredox suppression of, 311-312, 340-341, 344 synthesis of antifungal drugs active against, 331, 332-336 Polygonum hydropiper (Polygonaceae), 25 Polymerase chain reaction (PCR), 436 in split synthesis, encoding strategies, 277 Prazosin, 208 Prehalenaquinol, 171-172 Prehalenaquinone, 152, 171-173 dimethyl ether, 170 Prion proteins, 404 (S)-1, 2-Propanediol, dehydration of by diol dehydrases, 373, 374 Pteroenone, absolute stereochemistry from modified Mosher's method, 114 Ptychantin A, absolute stereochemistry from modified Mosher's method, 112 Putidaredoxin, 380 PU.1 (protein), 466-471 Pyridoxal 5'-phosphate (PLP), 363, 364, 365, 380, 384-386

Pyridoxamine-5'-phosphate (PMP), 352, 379, 380, 381, 383, 384-386 Pyridoxamine-5'-phosphate-∆3,4-glucoseen complex, 379, 380, 382, 383, 384, 385 Pyruvate, 364 Pyruvate-formate lyase, 377, 378 Q o-Quinodimethane, 162, 163, 166 R Ranitidine, 208 Raspailol A, absolute stereochemistry from modified Mosher's method, 114 Resonance Raman, studies of dihydroxy-acid dehydratase, 362 Retinal, 431 13-cis, 431, 433 9-demethyl, 432, 434 pigment formation with bacteriorhodopsin, 439-442 synthesis of, 438 13-demethyl, 432, 434 pigment formation with bacteriorhodopsin, 439-442 synthesis of, 438 9, 13-didemethyl, 432 pigment formation with bacteriorhodopsin, 439-442 synthesis of, 438 Rhodanthoside A, 80, 84-86 from Gentiana rhodantha, LC/MS of, 85 Rhodanthoside B, 80, 84-86 from Gentiana rhodantha, LC/MS of, 85 Rhodobacter capsulatus, fumarate hydratase from, 361 Ribonucleotide reductase, 351, 373, 375-378, 387 Rietone, absolute stereochemistry from modified Mosher's method, 113 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Rilmenidine, 290, 297 Ritterazine C, absolute stereochemistry from modified Mosher's method, 113 Rotational strength (Rba), 141 Rutales, order, 1 S Saccaromyces cerevisiae sesquiterpene dialdehyde effect on, 24, 25 Sanadaol, absolute stereochemistry from modified Mosher's method, 108, 109 Saraine A, absolute stereochemistry from modified Mosher's method, 116 Saraine B, absolute stereochemistry from modified Mosher's method, 116 Saraine C, absolute stereochemistry from modified Mosher's method, 116 Scout Scan, 95 Secoiridoids, 77, 79, 80 L-Selectride reductions, 233, 234 Sendanal, 3 Senile dementia, 76 L-Serine conversion to pyruvate, 363-364, 365 metabolism of, 363 methyl ester, modified Mosher's method applied to, 127 L-Serine dehydratase, 363, 364, 365, 384 Serotonin, 76 Serum, human determination of drugs in, 208-215 Sesquiterpene dialdehydes, 23-39 activity on plasma membrane, 35-37 antifeedant assay, 24 antifungal activity of, 27-36 oxidoredox suppression, 311-345

principles, isolation and identification of, 25 Canellaceae family, 24 congeners of, 25 bemadienolide, 25 cinnamosnolide, 25 colorata-4, 25 confertifolin, 25 8-dienolide, 25 epipolygodial, 25 9α-hydroxycinnamolide mukaadial, 25 muzigadial (canellal), 24 ugandensidial (cinnamodial), 25 structures, 25, 26 synergy, 29, 32 addition of excess Ca2+, 29, 31, 37 maesanin, antifungal activity of, 29 syntheses, 25 Warburgia genus, 24 antimicrobial activity of, 27 epipolygodial (C-9 epimer), 28 W. stulmannii, 24, 26 W. ugandensis, 24, 25 muzigadial (canellal), 24, 28 polygodial, 24, 25, 28, 36 warburganal, 24, 28, 33 Sharpless asymmetric epoxidation, 231, 232 Shikimate pathway, 355, 371 Sipholenol A, absolute stereochemistry from modified Mosher's method, 119-120

SOAK Assembly operation, 417 Solid phase synthesis, biphenyl scaffold, 281-283 Sorghum, 447 Southern army worm (see Spodoptera eridania (Boisduval)) Spacermectins, 263, 264, 267 Spin traps CP-H, 326 nitrones as, 324 TEMPONE-H, 326 Spinach, carbonic anhydrase from, 357 dihydroxy-acid dehydratase from, 362, 384 Spirosendan, 2 Split pool synthesis (see Combinatorial chemistry, split synthesis) Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Spodoptera S. eridania (Boisduval), (Southern army worm), 7, 9 S. exempta, 24 Squalene, 116 Squamostatin D, absolute stereochemistry from modified Mosher's method, 112 Squamostatin E, absolute stereochemistry from modified Mosher's method, 112 Stille coupling, in solid phase synthesis, 282, 283 Streptomyces avermitilis, 257 Striga, 450 S. asiatica, 447, 448 S. haustoria, 448 Suberitenone B, absolute stereochemistry from modified Mosher's method, 114 Sulfonyloxaziridines, synthesis of, 332 Superstolide A, absolute stereochemistry from modified Mosher's method, 112, 123, 124 Swerchirin (see Xanthone, 1, 8-dihydroxy3, 5-dimethoxy-) Sweroside, 79, 80, 84, 85, 93, 94, 95, 96, 97 7-β-[4'-O-(β-D-glucopyranosyl)-transcaffeoyloxy]- (corniculoside), 87 from Halenia corniculata, LC/ES-MS of, 89 from Halenia corniculata, LC/MS of, 88 from Halenia corniculata, LC/UV of, 89 from Chironia krebsii, LC/UV of, 81 from Gentiana rhodantha, LC/MS of, 85 from Swertia calycina, LC/NMR of, 93 from Swertia calycina, LC/UV of, 94 from Swertia calycina, WET-COSY of, 96 Swertia calycina antifungal activity of, 93, 96- 97 flavonoids of, 80, 87-93 LC/ES-MS analysis of, 90

LC/NMR analysis of, 93, 85-97 LC/TSP-MS analysis of, 90 LC/UV/MS analysis of, 87-93 Swertiajaponin, 80, 91, 93 from Swertia calycina, LC/MS of, 90 Swertiamarin, 79, 80 from Chironia krebsii, LC/UV of, 81 Swertisin, 80, 91, 93 from Swertia calycina, LC/MS of, 90 Swinholide A, absolute stereochemistry from modified Mosher's method, 110 T Tanabalin, modified Mosher's method applied to, 122-123 Tanacetum balsamita, 122 Tautomycin, application of modified Mosher's method during the synthesis of, 121-122 Tetrahydroxestoquinonol, 152 Tetranortriterpenoids, 1 TFE3 (protein), 466, 467, 469-471 Theophylline, 208 Thioredoxin, 376 Thioredoxin reductase, 383 L-Threonine conversion to β-ketobutyrate, 364, 365 methyl ester, modified Mosher's method applied to, 127 L-Threonine dehydratase, 363-364, 365, 384 Thymidine diphosphate-D-glucose 4, 5dehydratase, 364-367 Ti plasmid, 451-453 Titanium (III) citrate, (R)-2-hydroxylglutaryl-CoA dehydratase activation by, 367 Tobramycin, 208 Triazolam, 208

Trichilia roka (Meliaceae), 9 Trichilin, 2, 4, 9-11, 14-17 Trinoranastreptene, 143, 146 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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Trinorsesquiterpene, 142 Triterpenoids, 1 L-Tryptophan methyl ester, modified Mosher's method applied to, 127 Tyvelose, 378 U Ultra-violet spectroscopy post column addition of shifts reagents, 69-70 Uric acid, 216 Urine, human, determination of drugs in, 207-215 V L-Valine biosynthesis of, 362 methyl ester, modified Mosher's method applied to, 127 Vinylacetate-CoA, 369, 370 Virulence regulon, 452 Vitamin C, 208, 209 VBN-1, 340, 341 VBN-2 (macrobicyclic oxaziridine), 333-335, 337, 340, 341, 344, 345 VBN-3, 326-327, 335, 336, 340, 341, 344, 345 VBN-4, 335, 336, 340, 341 VBN-5-9, 337, 340, 341 VBN-10, 331, 337, 339, 340, 341 VBN-11-14, 340, 341 Vogelside, 80, 87 from Halenia corniculata, LC/MS of, 88 epi-Vogelside, 80, 87 from Halenia corniculata, LC/MS of, 88 W

Wailupemycin A, absolute stereochemistry from modified Mosher's method, 116 Warburganal, 23, 221 attempted synthesis of, 221-222 synthesis of, 223-224 Warburgia W. stuhlmannii, 24 W. ugandensis, 24, 221 WET (water suppression enhanced through T1 effect), 73, 95, 96, 97 Wieland–Miescher ketone, 147, 163, 164, 165, 169 X Xanthone as MAO inhibitors, 76-77 1, 8-dihydroxy-3, 5-dimethoxy- (swerchirin), 77 1, 5-dihydroxy-3-methoxy-, 79, 80, 84 from Chironia krebsii, LC/UV of, 81 inhibition of MAO-A, 84 1, 7-dihydroxy-3-methoxy- (gentisin), 77-78 7, 8-dihydroxy-3-methoxy-1-O-primeverosyl-, 79, 80 from Chironia krebsii, LC/UV of, 81 1, 6-dihydroxy -3, 5, 7, 8-tetramethoxy-, 79, 80 from Chironia krebsii, LC/UV of, 81 3, 5-dimethoxy-1-O-primeverosyl-, 79, 80 from Chironia krebsii, LC/UV of, 81 1-O-glucosyl-5-hydroxy-3-methoxy-, 79, 80 from Chironia krebsii, LC/UV of, 81 1-hydroxy-3-methoxy-5-O-primeverosyl-, 79, 80, 83, 84 from Chironia krebsii, LC/UV of, 81, 82 from Chironia krebsii, LS/TSP-MS of, 82 5-hydroxy-3-methoxy-1-O-primeverosyl-, 79, 80, 83, 84

from Chironia krebsii, LC/UV of, 81 from Chironia krebsii, LC/TSP-MS of, 82 1-hydroxy-3, 5, 6, 7, 8 -pentamethoxy-, 79, 80, 83, 93, 94, 95 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation

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[Xanthone] from Chironia krebsii, LC/UV of, 81 from Chironia krebsii, LC/TSP-MS of, 81 from Swertia calycina, LC/NMR of, 93 from Swertia calycina, LC/UV of, 94 1-hydroxy-3, 7, 8-trimethoxy-, (decussatin), 79, 80, 83 from Chironia krebsii, LC/UV of, 82 from Chironia krebsii, LC/TSP-MS of, 82 3-methoxy-1, 5, 8-trihydroxy-, (bellidifolin), 77 3-methoxy-1, 7, 8-trihydroxy-, 79, 80, 83 from Chironia krebsii, LC/TSP-MS of, 82 from Chironia krebsii, LC/UV of, 81, 82 2, 3, 4, 5, 7-pentamethoxy-1-O-primeverosyl-, 79, 87 from Halenia corniculata, LC/MS of, 88 3, 5, 6, 7, 8-pentamethoxy-1-O-primeverosyl-, 79, 80, 83 from Chironia krebsii, LC/TSP-MS of, 81 from Chironia krebsii, LC/UV of, 81 1-O-primeverosyl-2, 3, 4, 5-tetramethoxy-, 80, 87 from Halenia corniculata, LC/MS of, 88 1-O-primeverosyl-2, 3, 4, 7-tetramethoxy-, 80, 87 from Halenia corniculata, LC/MS of, 88 1-O-primeverosyl-2, 3, 5-trimethoxy-, 80, 87 from Halenia corniculata, LC/MS of, 88 1-O-primeverosyl-2, 3, 7-trimethoxy-, 80, 87 from Halenia corniculata, LC/MS of, 88 1, 3, 5, 8-tetrahydroxy-, (desmethylbellidifolin), 77 1, 3, 7, 8-tetrahydroxy-, 79, 80 from Chironia krebsii, LC/UV of, 81 1, 3, 7-trihydroxy-, 79, 80

from Chironia krebsii, LC/UV of, 81 Xenognosin, 447, 448 Xenognosis, 447 receptor, 453 signals, 448 Xestoquinol, 153 dimethyl ether, 170 synthesis of, 170-171 Xestoquinone, 152 synthesis of, 169-171 Xestospongia exigua, 151 Xestospongia sapra, 152, 172 X-ray crystallography Bijovet method, 140, 151 Y Yeast enolase from, 358 fumarate hydratase from, 361 Yersinia pseudotuberculosis, biosynthesis of ascarylose by, 378 thymidine diphosphate-D-glucose 4, 5 -dehydratase from, 365 Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation