The Alkaloids: Chemistry and Pharmacology 39

377 Pages·1990·12.82 MB·English

by  Arnold Brossi (Eds.)

THE ALKALOIDS
Chemistry and Pharmacology
VOLUME 39
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THE ALKALOIDS
Chemistry and Pharmacology
Edited by
Arnold Brossi
National Institutes of Health
Bethesda. Maryland
VOLUME 39
Academic Press, Inc.
Harcourt Brace Jovanovich, Publishers
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London Sydney Tokyo Toronto
This book is printed on acid-free paper. @
COPYRIGHT 0 1990 BY ACADEh4IC PRESS, INC.
All Rights Reserved.
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ACADEMIC PRESS, INC.
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United Kingdom Edition published by
ACADEMIC PRESS LIMITED
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LIBRARY OF CONGRESS CATALOG CARD NUMBER: 50-5522
ISBN 0-12-469539-6 (alk. paper)
PRINTED IN THE UNITED STATES OF AMERICA
90919293 1 0 9 8 1 6 5 4 3 2 1
CONTENTS
CONTRIBUTOR..S. ........... .............................. ix
PREFACE. .................. .............................. xi
Chapter 1. Betalains
WOLFGANSGT EGLICHA ND DIETERS TRACK
I. Introduction ....................................................... 1
11. Structural Elucidation and Chemistry of Betanidin ...... 3
111. Betacyanins ...................................... 8
IV. Betaxanthine ............................................. 19
V. Muscapurpurin . .................... 26
VI. Betalamic Acid . .................... 26
VII. Muscaflavin ......................... ............... 21
VIII. Syntheses of Betalains ............................................... 28
IX. Chemotaxonomy and Distribution of Betalains ........... 35
X. Biosynthesis of Betalains ........................ 53
References ........................................................ 59
Chapter 2. Benzodiazepine Alkaloids
W. Ross
1. Introduction .............................................. 63
robial Producers ........... ......... 66
111. Structural Elucidation and Related Chemistry ............................ 66
IV. Biosynthesis ....................................................... 73
V. Metabolic Conversion of Benzo 79
VI. Physiological Aspects ....... ........... 81
VII. Biological Activity of Naturally 93
References ........................................ 94
Chapter 3. Phenanthrene Alkaloids
LUISC ASTEDOA ND GABRIELT OJO
I. Introduction ....................................................... 99
11. Occurrence and Structures ............................................ 100
V
vi CONTENTS
111. Synthesis . . . . . . . . . . . . . 121
128
V. Biosynthesis . . . . . . . . . . . . . . . . . . . . 132
134
VII. Pharmacology ............................................. 135
References . . . . . . . . . . . . . . . . . . . 135
Chapter 4. The Alkaloids of Khat (Carha edulis)
L. CROMBIEW, . M. L. CROMBIEA, ND D. A. WHITING
1. Introduction ....................................................... 139
11. The Phenylalkylamine Alkaloids (Khatamines) . . . . . . . . . . . . . . . . I 40
I
111. Synthesis of the Khatamines . . . . 141
IV. Pharmacological Action of the Khatamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
V. The Cathedlin Alkaloids of Khat 145
VI. Triterpenoid Extractives of Khat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
VII. The Catvaalens Sesquiterpenoids of Cuthu trunsvuulensis . . . . . . . . . . . . . . . . . . 159
VIII. Synthetic Work Relevant to the Cathedulin Alkaloids .... 159
References ........................................................ 162
Chapter 5. Histochemistry of Alkaloids
YOHEIH ASHIMOTOK,A ZUKOK AWANISHAI,N D MOMOYOIC HIMARU
I. Introduction ....................................................... 165
11. Histochemistry ..................................................... 167
111. Histochemical Chromatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
References ........................................................ 191
Chapter 6. Taxus Alkaloids
SIEGFRIEBDL ECHERATN D DANIELG UENARD
I. Introduction . . . . . . . . . . . .............................. 195
11. Structure ...................................................... 196
111. Isolation . . . ............................................ 197
202
V. Hemisynthesis ...................................................... 203
VI. Synthesis . . . . . . . . . . . . . . .............................. 208
VII. Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . 229
References ........................................................ 234
Chapter 7. Synthesis and Antitumor Activity of the Ellipticine
Alkaloids and Related Compounds
GORDONW . GRIBBLE
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
11. Occurrence and Structural Determination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
CONTENTS vii
111. Synthesis of Ellipticine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
IV. Synthesis of Olivacine . . . . . . . . . . . . . . . . . . . . . , . . , . , . . . . . . . . . . . . . . , . . . . . 250
V. Synthesis of Modif cine Derivatives . . . . . . . . . . ...... 254
VI. Biological Detectio ........................................... 305
VII. Antitumor Activity mental Models . . . . . . , . , . . . . . . . . . . . . . . . . . . . . 307
VIII. Mechanism of Action . . . . . . . . . . . . . . . . . 31 I
IX. Mutagenicity ................................................... 325
X. Metabolism and Microbial Transformation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
XI. Structure-Activity Relationships . . . . . . . . . . 328
............................... 340
XIII. Clinical Trials , . . . . . . , . ............................... 340
XIV. Conclusion ............................... 343
............................... 343
CUMULATIVE INDEX OF TITLES. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
INDEX .................................................................. 36 I
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CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors’ contributions begin.
SIEGFRIEDBL ECHER(T1 95), Institut fur Organische Chemie Universitat Bonn,
D-5300 Bonn 1, Federal Republic of Germany
LUISC ASTEDO(9 9), Department of Organic Chemistry, University of Santiago
de Compostela, Santiago, Spain
L. CROMBIE(1 39), Department of Chemistry, The University of Nottingham,
Nottingham, NG7 2RD, England
W. M. L. CROMBIE(1 39), Department of Chemistry, The University of Not-
tingham, Nottingham, NG7 2RD, England
GORDONW . GRIBBLE(2 39), Department of Chemistry, Dartmouth College,
Hanover, New Hampshire 03755
DANIELG UENARD( 195), Institut de Chimie des Substances Naturelles,
C.N.R.S., F-91190 Gif-sur-Yvette, France
YOHEIH ASHIMOT(O1 65), Kobe Women’s College of Pharmacy, Motoyamakita-
Machi, Higashinada-Ku, Kobe 658, Japan
MOMOYOIC HIMAR(U1 63, Kobe Women’s College of Pharmacy, Motoyamakita-
Machi, Higashinadu-Ku, Kobe 658, Japan
KAZUKOK AWANISH(1I 63, Kobe Women’s College of Pharmacy, Motoyama-
kita-Machi, Higashinadu-Ku, Kobe 658, Japan
W. Ross (63), Biotechnikum, Martin-Luther-Universitat Halle-Wittenberg, 4050
Halle (Saale), German Democratic Republic, Federal Republic of Germany
WOLFGANGST EGLIC(Hl) , Institut fur Organische Chemie und Biochemie, Uni-
versitat Bonn, D-5300 Bonn 1, Federal Republic of Germany
DIETERS TRACK(l ), Institut fur Pharmazeutische Biologie, Technische Univer-
sitat Braunschweig, D-3300 Braunschweig, Federal Republic of Germany
GABRIELT OJO( 99), Department of Organic Chemistry, University of Santiago
de Compostela, Santiago, Spain
D. A. WHITING(1 39), Department of Chemistry, The University of Nottingham,
Nottingham, NG7 2RD, England
ix