The Alkaloids: Chemistry and Pharmacology 21

389 Pages·1983·15.79 MB·English

by  Arnold Brossi (Eds.)

THE ALKALOIDS
Chemistry and Pharmacology
Volume XXI
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THE ALKALOIDS
Chemistry and Pharmacology
Edited by
Arnold Brossi
National Institutes of Health
Berhesda. Maryland
Founding Editor
R. H. F. Manske
VOLUME XXI
1983
ACADEMIC PRESS
A Subsidiary of Harcourt Brace Jovanovich, Publishers
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ACADEMIC PRESS, INC. (LONDON) LTD.
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ISBN 0-12-469521-3
PRINTED IN THE UNITED STATES OF AMERICA
83 84 85 X6 9 8 7 6 5 4 3 2 1
CONTENTS
LISTO F CONTRIBUTOR.S . . . . . . . . . . . . . . . . . . . . . . . . . ix
PREFACE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
...
CONTENTOSF PREVIOUVSO LUMES. . . . . . . . . . . . . . . . . . . . . . xi11
Chapter 1 . Acridone Alkaloids: Experimental Antitumor Activity of Acronycine
KOERTG ERZONA ND GORDONH . SVOBODA
1. Historical Introduction . . . . . . . . . . . . . . . . . . . . . . . . 1
I1 . Physical and Chemical Properties . . . . . . . . . . . . . . . . . . . 4
111 . Structure of Acronycine: Principal Syntheses . . . . . . . . . . . . . . . 5
1V. Experimental Antitumor Activity of Acronycine . . . . . . . . . . . . . 1
V . Structure-Activity Relationships (SAR) . . . . . . . . . . . . . . . . . 11
VI . Mammalian Metabolism . . . . . . . . . . . . . . . . . . . . . . . 13
V11 . Preclinical Studies of Acronycine . . . . . . . . . . . . . . . . . . . 16
VIII . Mechanism of Action . . . . . . . . . . . . . . . . . . . . . . . . 18
IX . Summary and Conclusions . . . . . . . . . . . . . . . . . . . . . . 22
Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Addendum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Chapter 2 . The Quinazolinocarboline Alkaloids
JANB ERGMAN
I . Introduction and Nomenclature . . . . . . . . . . . . . . . . . . . . 29
I1 . Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
111 . Structure and Synthesis . . . . . . . . . . . . . . . . . . . . . . . 36
IV. Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
V. Pharmacological Properties of Quinazolinocarboline Alkaloids and
Synthetic Analogs . . . . . . . . . . . . . . . . . . . . . . . . . . 49
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
vi CONTENTS
Chapter 3. Isoquinolinequinones from Actinomycetes and Sponges
TADASHAIR AIA ND AKINORKIU BO
I. Introduction and Occurrence . . . . . . . . . . . . . . . . . . . . . 56
11. Saframycin-Type Antibiotics . . . . . . . . . . . . . . . . . . . . . 57
Ill. Renieramycin-Type Antibiotics . . . . . . . . . . . . . . . . . . . . 71
1V. Naphthyridinomycin-Type Antibiotics . . . . . . . . . . . . . . . . . . 75
V. Mimosamycin-Type Antibiotics . . . . . . . . . . . . . . . . . . . . 78
VI. Biological Activity . . . . . . . . . . . . . . . . . . . . . . . . . 89
Addendum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Chapter 4. Camptothecin
JUN-CHACOA IA ND C. RICHARHDU TCHINSON
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
11. Total Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . I04
111. Biogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
IV. Medicinal Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . 123
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Chapter 5. Amphibian Alkaloids
BERNHARWDI TKOPA ND EDDAG OSSINGER
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
11. Location and Function of Amphibious Venoms: Steroidal Alkaloids, Tetrodotoxin 141
111. Spiropiperidines, cis-Decahydroquinolines, and Octahydroindolizidines . . . . 168
IV. Neurotoxins, Receptors, and Ion Transport . . . . . . . . . . . . . . . . 219
V. Epilogue. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
Addendum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
Chapter 6. Simple Isoquinoline Alkaloids
JANL UNDSTROM
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
11. Simple Isoquinoline Alkaloids . . . . . . . . . . . . . . . . . . . . . 256
111. 1 -Phenyl-, 4-Phenyl-, and N-Benzyl-Substituted Simple Isoquinoline Alkaloids . 303
1V. Biogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312
V. Biological Effects . . . . . . . . . . . . . . . . . . . . . . . . . . 318
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
CONTENTS vii
Chapter 7 . Mammalian Alkaloids
MICHAEAL . COLLINS
I . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
I1 . Chemical Considerations . . . . . . . . . . . . . . . . . . . . . . . 332
111 . Analytical Separation and Detection of Mammalian Alkaloids . . . . . . . . 335
IV. Production of 1.2.3. 4.Tetrahydroisoquinolines in Vim . . . . . . . . . . . 339
V . Tetrahydroisoquinolines in Human and Animal Models . . . . . . . . . . . 341
VI . Mammalian (3-Carboline Formation . . . . . . . . . . . . . . . . . . . 343
VII . Alternative Modes of Mammalian Alkaloid Formation . . . . . . . . . . . 344
VIII . Metabolic Studies of Mammalian Alkaloids . . . . . . . . . . . . . . . 346
IX . Effects of Mammalian Alkaloids on Biochemical Processes . . . . . . . . . 349
X . Physiological and Behavioral Effects of Mammalian Alkaloids . . . . . . . 350
XI . Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
INDEX . . . . . 359
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LIST OF CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors’ contributions begin
TADASHAI RAI( 53, Department of Antibiotics, Research Institute for Chemo-
biodynamics, Chiba University, Chiba, Japan
JANB ERGMAN(2 9), Department of Organic Chemistry, Royal Institute of Tech-
nology, S-100 44 Stockholm, Sweden
JUN-CHAOCA I*( 101), School of Pharmacy, University of Wisconsin, Madison,
Wisconsin 53706
MICHAEL A. COLLINS( 329), Department of Biochemistry and Biophysics,
Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois
60153
EDDA GOSSINGER( 139), Institut fur Organische Chemie, Universitat Wien,
Vienna, Austria
KOERTG ERZON( l), Department of Pharmacology, Indiana University School of
Medicine, Indianapolis, Indiana 46223
C. RICHARDH UTCHINSO(N1 01), School of Pharmacy, University of Wisconsin,
Madison, Wisconsin 53706
AKINORKI UBO (55), Department of Organic Chemistry, Meiji College of
Pharmacy, Tokyo, Japan
JAN LUNDSTROM(2 55), Astra Pharmaceuticals, Sodertalje, Sweden and Depart-
ment of Pharmacognosy , Faculty of Pharmacy, Uppsala University, Uppsala,
Sweden
GORDONH . SVOBODA(l ), Indianapolis, Indiana 46226
BERNHARDW ITKOP( 139), National Institutes of Health, Bethesda, Maryland
20205
*Present address: Department of Medicinal Chemistry, Shanghai Institute of Materia Medica,
Academia Sinica, Shanghai, 200031, People’s Republic of China.
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