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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

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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

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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

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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

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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

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Contents

Preface iii

Contributors ix

Tribute Letters xiii

1. Insect Antifeeding Limonoids from the Chinaberry Tree Melia azedarach 1


Linn. and Related Compounds
Munehiro Nakatani

2. Polygodial and Warburganal, Antifungal Sesquiterpene Dialdehydes and 23


Their Synergists
Isao Kubo

3. Marine Bromoperoxidases—Chemoenzymatic Applications 43


Chris A. Moore and Roy K Okuda

4. LC-Hyphenated Techniques in the Search for New Bioactive Plant 65


Constituents
Kurt Hostettmann, Maryse Hostettmann, Sylvain Rodriguez, and Jean-Luc
Wolfender

5. Determination of the Absolute Configuration of Biologically Active 103


Compounds by the Modified Mosher's Method
Takenori Kusumi and Ikuko I. Ohtani

6. Circular Dichroism Spectroscopy and the Absolute Stereochemistry of 139


Biologically Active Compounds
Nobuyuki Harada

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7. Recent Applications of Circular Dichroism to Carbohydrate 191


Conformational Analysis and Direct Determination of Drug Levels
Jesús Trujillo Vázquez

8. Furan-Terminated Cationic π-Cyclizations in the Synthesis of Natural 221


Products
Steven P. Tanis

9. Chemistry and Biology of Semisynthetic Avermectins 257


Timothy A. Blizzard

10. Chemical and Biological Approaches to Molecular Diversity: 271


Applications to Drug Discovery
Harold V. Meyers

11. Imidazoline Receptors and Their Endogenous Ligands 289


Colin J. Barrow And Ian F. Musgrave

12. Oxidoredox Suppression of Fungal Infections by Novel 311


Pharmacophores
Valeria Balogh-Nair

13. A Mechanistic Analysis of C—–O Bond Cleavage Events with a 351


Comparison to 3,6-Dideoxysugar Formation
David A. Johnson and Hung-Wen Liu

14. The Molecular Mechanism of Amyloidosis in Alzheimer's Disease 397


Michael G. Zagorski

15. Bacteriorhodopsin Structure/Function Studies: Use of the Demethyl 431


Retinal Analogues for Probing of the Arg82Ala Mutant
Rosalie K Crouch, Donald R. Menick, Yan Feng, Rajni Govindjee, And
Thomas G. Ebrey

16. Autonomous Genomes 445


David G. Lynn

17. Stereochemical Considerations of Immunoglobulin Heavy Chain 461


Enhancer Activation
Barbara S. Nikolajczyk And Ranjan Sen

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 Urbana-
Champaign, 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

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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

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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.

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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

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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

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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.

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Index

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

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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

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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 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

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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

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

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Page 477

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
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Page 478

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

(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

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

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Page 479

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

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

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

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Page 480

[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

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Page 481

(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

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

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Page 482

[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

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Page 483

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

Jaspiferal A, absolute stereochemistry from modified Mosher's method, 114

Junicedranol, absolute stereochemistry from modified Mosher's method, 116

3-Ketoadociaquinone A, 152

a-Ketoglutarate, 364

Kinetic resolution, 107

Krebs cycle (citric acid cycle), 359, 361

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

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Page 484

[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

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

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Page 485

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

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Page 486

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

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

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

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Page 487

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

o-Quinodimethane, 162, 163, 166

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

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Rilmenidine, 290, 297

Ritterazine C, absolute stereochemistry from modified Mosher's method, 113

Rotational strength (Rba), 141

Rutales, order, 1

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)

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Page 489

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

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

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Trinorsesquiterpene, 142

Triterpenoids, 1

L-Tryptophan methyl ester, modified Mosher's method applied to, 127

Tyvelose, 378

Ultra-violet spectroscopy

post column addition of shifts reagents, 69-70

Uric acid, 216

Urine, human, determination of drugs in, 207-215

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

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

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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

Yeast

enolase from, 358

fumarate hydratase from, 361

Yersinia pseudotuberculosis,

biosynthesis of ascarylose by, 378

thymidine diphosphate-D-glucose 4, 5

-dehydratase from, 365

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