The Alkaloids: Chemistry and Pharmacology 46

381 Pages·1995·13.85 MB·English

by  Geoffrey A. Cordell (Eds.)

THE ALKALOIDS
Chemistry and Pharmacology
VOLUME 46
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THE ALKALOIDS
Chemistry and Pharmacology
Edited by
Geoffrey A. Cordell
College of Pharmacy
University of Illinois at Chicago
Chicago, Illinois
VOLUME 46
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CONTRIBUTO.R..S.. .................................................................................. vii
PREFAC.E.. .............................................................................................. ix
Chapter I. Biosynthesis of Pyrrolizidine and Quinolizidine Alkaloids
DAVIDJ . ROBINS
I. Introduction ........... ........ 1
11. Pyrrolizidine Alkaloi ........ 3
111. Quinolizidine Alkaloids ................................................................... 36
IV. Conclusions ......... ................................................................ 55
Addendum .................................................. ............................ 56
References .................................................................................... 57
Chapter 2. Pharmacology of Polyamine Toxins from Spiders and Wasps
ALANL . MUELLER,R OSEMARIREO ELOFFSA, ND HUNTERJA CKSON
I. Introduction and Ecological Aspects ................................................. 63
11. Pharmacological Effects of Polyamine Toxins in Invertebrates ............... 61
111. Pharmacological Effects of Polyamine Toxins in Vertebrates ................. 12
IV. Structure-Activity Relationship Studies ............................................. 86
V. Perspectives .................................................................................. 90
References .................................................................................... 91
Chapter 3. Epibatidine
CSABAS ZANTAYZ,S UZSANNKAA RDOS-BALOGAHN,D CSABAS ZANTAYJR, .
I. Introduction .................................................................................. 95
11. Occurrence .......................... .......... %
111. Structure and Syntheses .................................................................. %
IV. NMR Spectroscopy ........................................................................ I16
V. Pharmacology ................................................. I I9
Addendum ..................................................... 123
References ......... ................................................................. I24
V
vi CONTENTS
Chapter 4. The Naphthylisoquinoline Alkaloids
GERHARD BRINCMANANN D FRANPKO KORNY
I. Introduction .... . .. .. . .. .. .. ... . .. . ... . .. .. .. ... . .. . ... . .. .. . ... . .. .. .. .. . .. ... . .. . ... . .. .. . .. 128
11. Isolation and Structure Elucidation of Naphthylisoquinoline
Alkaloids: Dioncophylline A ("Triphyophyll 130
111. Other Alkaloids from the Dioncophyllaceae 146
.....................
1V. New Alkaloids from Asian Ancistrocladace 156
V. Alkaloids of African Ancistrocladaceae Species.. .. .. .. .. . .. .. 158
VI. The Michellamine: A New Class of Naturally Occurring
Quateraryls and Related Compounds .. . . . . . . . . . .. . .................... 170
VII. Stereocontrolled Synthesis of Mono- and Dimeric
Naphthylisoquinoline Alkaloids .. .. .. . . .. .. . . .. . .. . . . . .. . .. . . .. .. . . .. . .. .. . . .. . .. .. . . . . 180
VIII. Biogenetic Origin of Naphthylisoquinoline Alkaloids ..... 200
IX. The Chemo-ecological Context of Naphthylisoquinoline 21 1
X. Tables of Known Natural Naphthylisoquinoline Alkaloids ....... .. .. .. .. . .. ... 216
XI. Summary and Outlook ..................... ................... ...... 254
XII. Addendum .................................................................................... 255
References .. . . .. . . .. ............................................... 263
Chapter 5. The Biotransformation of Protoberberine Alkaloids
by Plant Tissue Cultures
KINUKOIW ASA
I. Introduction ... . .. .. .. . . .. . .. .. .. .. .. .. . . .. . .. .. .. .. .. .. . .. .. .. .. .. .. . .. .... . .. . .. .. .. .. . .. .. . 273
11. The First Pathway .......................................................................... 277
111. The Second Pathway .................................................. ............ 329
IV. The Third Pathway ......................................................................... 333
References .. .. . . . . . .. ................... ................... 345
CUMULATIVINED EX OF TITLES.. .............................................................. 347
INDEX .................................................................................................. 355
CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors’ contributions begin.
GERHARDB RINGMAN(1N2 7) Institut fur Organische Chemie der Uni-
versitat Wurzburg Am Hubland, D-97074 Wurzburg, Germany
KINUKOIW ASA(2 73) Laboratory of Pharmaceutical Chemistry, Kobe
Pharmaceutical University, Higashinada, Kobe 658, Japan
HUNTERJA CKSO(N63 ) NPS Pharmaceuticals, Inc., Salt Lake City, Utah
84108
ZSUZSANNKAA RDOS-BALO(G95H) Central Research Institute for Chem-
istry of the Hungarian Academy of Sciences, H-1525 Budapest, Hungary
ALANL . MUELLER( 63) NPS Pharmaceuticals, Inc., Salt Lake City,
Utah 84108
FRANKP OKORN(Y12 7) Institut fur Organische Chemie der Universitat
Wurzburg Am Hubland, D-97074 Wurzburg, Germany
DAVIDJ. ROBIN(S1 ) Department of Chemistry, University of Glasgow,
Glasgow G12 SQQ, United Kingdom
ROSEMARRIEO ELOFF(S6 3) NPS Pharmaceuticals, Inc., Salt Lake City,
Utah 84108
CSABAS ZANTAY(9 5) Central Research Institute for Chemistry of the
Hungarian Academy of Sciences, H- 1525 Budapest, Hungary
CSABAS ~ANTAJYR,. (95) Spectroscopic Department, Chemical Works
of Gedeon Richter, H-1475 Budapest, Hungary
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PREFACE
This volume of The Alkaloids recognizes that a primary goal of alkaloid
research is making compounds available for potential therapeutic or bio-
logical use for the benefit of humankind. The motivation that leads to the
discovery of novel, biologically active compounds occasionally yields
“hot” topics, areas of research that attract substantial attention and a
flurry of scientific activity. Three of the chapters in this volume of the series
reflect that level of current interest, spider toxins, naphthylisoquinoline
alkaloids, and epibatidine. Three different sources of biologically signifi-
cant compounds, arachnids, higher plants, and frog skin, have yielded
these alkaloids, which, in the future, may have a significant effect in three
quite different areas of biological focus, CNS disorders, anti-HIV, and
analgesia. Jackson and co-workers review the progress that has been made
on understanding the biology of certain spider toxins and their derivatives,
while Bringmann and Pokorny delineate the progress made in the structure
elucidation, synthesis, and biological activity of the monomeric naphthyl-
isoquinoline alkaloids. SzAntay reviews the very interesting, non-narcotic
analgesic epibatidine, particularly the advances that have been made in
developing effective synthetic procedures for analog work.
The two remaining chapters reflect our innate desire, as an integral part
of alkaloid chemistry, to understand how alkaloids are produced from
their simple amino acid precursors and to discern how one group of metab-
olites may serve as a point of structural diversification for many other
metabolites. Robins reviews the biosynthesis of the pyrrolizidine and
quinolizidinea lkaloids showing how these structurally analogous alkaloids
have quite different biosynthetic pathways, while Iwasa comments on the
progress made in understanding the precursor relationships and enzymatic
control of the molecular acrobatics of the protoberberine alkaloids in
yielding other important alkaloid classes.
Geoffrey A. Cordell
University of Illinois at Chicago
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