The Biology-chemistry Interface a Tribute to Koji Nakanishi - Raymond Cooper, John K. Snyder

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

(1S, 8aR)-(+)-1, 8a-dihydro-1-methoxy-6, 8a-dimethyl-, 143, 147-148
(1S, 8aR)-(+)-1, 8a-dihydro-1-methoxy-8a-methyl-, 143, 147-148
(1S, 8aR)-( + )-1, 8a-dihydro-8a-methyl-, 143, 148-151
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
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

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
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
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

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

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/UV analysis of, 77-78

Gentiana rhodantha, 84-86
LC/UV analysis of, 84
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

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
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
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
amiloride, 294
I2A-sites, 294

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
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

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
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

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
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

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
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
2-Nitrophenol, (R)-2-hydroxylglutaryl-CoA dehydratase inhibition by, 367

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

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

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
synthesis of, 438
9, 13-didemethyl, 432
synthesis of, 438
Rhodanthoside A, 80, 84-86
Rhodanthoside B, 80, 84-86
Rhodobacter capsulatus, fumarate hydratase from, 361
Ribonucleotide reductase, 351, 373, 375-378, 387
Rietone, absolute stereochemistry from modified Mosher's method, 113

Page 488
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
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)

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/UV of, 89
from Chironia krebsii, LC/UV of, 81
from Swertia calycina, LC/NMR of, 93
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
Swertiajaponin, 80, 91, 93
Swertiamarin, 79, 80
Swertisin, 80, 91, 93
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
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

Page 490
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
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
epi-Vogelside, 80, 87
W
Wailupemycin A, absolute stereochemistry from modified Mosher's method, 116
Warburganal, 23, 221
attempted synthesis of, 221-222
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
inhibition of MAO-A, 84
1, 7-dihydroxy-3-methoxy- (gentisin), 77-78
7, 8-dihydroxy-3-methoxy-1-O-primeverosyl-, 79, 80
1, 6-dihydroxy -3, 5, 7, 8-tetramethoxy-, 79, 80
3, 5-dimethoxy-1-O-primeverosyl-, 79, 80
1-O-glucosyl-5-hydroxy-3-methoxy-, 79, 80
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/TSP-MS of, 82
1-hydroxy-3, 5, 6, 7, 8
-pentamethoxy-, 79, 80, 83, 93, 94, 95

Page 491
[Xanthone]
from Swertia calycina, LC/NMR of, 93
1-hydroxy-3, 7, 8-trimethoxy-, (decussatin), 79, 80, 83
3-methoxy-1, 5, 8-trihydroxy-, (bellidifolin), 77
3-methoxy-1, 7, 8-trihydroxy-, 79, 80, 83
from Chironia krebsii, LC/UV of, 81, 82
2, 3, 4, 5, 7-pentamethoxy-1-O-primeverosyl-, 79, 87
3, 5, 6, 7, 8-pentamethoxy-1-O-primeverosyl-, 79, 80, 83
1-O-primeverosyl-2, 3, 4, 5-tetramethoxy-, 80, 87
1-O-primeverosyl-2, 3, 4, 7-tetramethoxy-, 80, 87
1-O-primeverosyl-2, 3, 5-trimethoxy-, 80, 87
1-O-primeverosyl-2, 3, 7-trimethoxy-, 80, 87
1, 3, 5, 8-tetrahydroxy-, (desmethylbellidifolin), 77
1, 3, 7, 8-tetrahydroxy-, 79, 80
1, 3, 7-trihydroxy-, 79, 80
Xenognosin, 447, 448
Xenognosis, 447
receptor, 453
signals, 448
Xestoquinol, 153
dimethyl ether, 170
Xestoquinone, 152
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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Start of Citation[PU]Marcel Dekker[/PU][DP]1999[/DP]End of Citation