Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products

339 Pages·1993·10.686 MB·English

by  Prof. S. V. Bhat, Prof. L. Minale, Dr. R. Riccio, Dr. F. Zollo (auth.), Prof. W. Herz, Prof. G. W. Kirby, Prof. R. E. Moore, Prof. Dr. W. Steglich, Prof. Dr. Ch. Tamm (eds.)

Fortschritte del' Chemie organischer Naturstoffe
Progress in the
Chemist~
of Organic Natural Products
6 2
Founded L. Zeehmeister
,,~
Edited ,,~ W. Herz, O. W. Kir~, R. E. Moore,
W. Steglieh, and Ch. ramm
Authors:
S. V. Bhat, L. Minale, R. Riceio, F. Zollo
Springer-Verlag
Waen New¥orll Iff]
Prof. W. HERZ, Department of Chemistry,
The Florida State University, Tallahassee, Florida, U.S.A.
Prof. G. W. KIRBY, Chemistry Department,
The University, Glasgow, Scotland
Prof. R. E. MOORE, Department of Chemistry,
University of Hawaii at Manoa, Honolulu, Hawaii, U.S.A.
Prof. Dr. W. STEGLICH, Institut fur Organische Chemie der Universitat
Munchen, Munchen, Federal Republic of Germany
Prof. Dr. CH. TAMM, Institut fiir Organische Chemie der Universitiit Basel,
Basel, Switzerland
This work is subject to copyright.
All rights are reserved. whether the whole or part of the material is concerned, specifically those
of translation, reprinting, re-use of illustrations. broadcasting, reproduction by photocopying
machines or similar means, and storage in data banks.
© 1993 by Springer-VerlaglWien
Softcover reprint of the hardcover 1st edition 1993
Library of Congress Catalog Card Number AC 39-1015
Typesetting: Macmillan India Ltd. • Bangalore-25
Printed on acid free paper
With 52 Figures
ISSN 0071-7886
ISBN-13: 978-3-7091-9252-8 e-ISBN-13: 978-3-7091-9250-4
DOl: 10.1007/978-3-7091-9250-4
Contents
List of Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. VII
Forskolin and Congeners.
By SUJATA V. BHAT ...
I. Introduction . . . . 3
II. Isolation and Structure Determination. . . . . . . . . 4
III. Botanical and Biogenetic Consideration. . . . . . . . . . . . . . . . . . . . . .. 7
IV. Chemistry of Forskolin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 10
i) Acylation and Alkylation Reactions. . . . . . . . . . . . . . . . . . . . . . .. 10
ii) Oxidations and Reductions ........................... , 15
iii) Biological Oxidations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20
iv) Isomerisation, Fragmentation and Rearrangements ............. , 20
V. Synthesis of Forskolin . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
i) Approaches to the AB Ring System of Forskolin .............. , 25
Intramolecular Diels-Alder (IMDA) Strategy ................. , 25
Intermolecular Diels-Alder Strategy . . . . . . . . . . . . . . . . . . . . . .. 28
Intermolecular Nitrile Oxide Cycloaddition Approach. . . . . . 30
Intramolecular Radical Mediated Cyclization Followed by
Mukiyama Aldolization . . . . . . . . . . . . . . . . . . . . . . . . 30
Intramolecular Michael-Aldol Condensation Strategy . . . . . . 30
Intramolecular Olefin CyClization ....................... ' 33
ii) Approaches to the ABC Ring System of Forskolin ............. , 35
iii) Total Synthesis of Forskolin . . . . . . . . . . . . . . . . . . . . . 36
Ziegler's Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ., 36
Ikegami's Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 36
Corey's Approach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 37
VI. Biological Activities of Forskolin. . . . . . . . . . . . . . . . . . . . . . . . . .. 43
i) Activation of Adenylate Cyclase. . . . . . . . . . . . . . . . . . . . 43
ii) Pharmacological Activities with Therapeutic Significance. . . . . . . . ... 44
iii) Modulation of Membrane Transport Proteins. . . . . . . . . . . . . . . .. 46
iv) Effect on Cell Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 47
v) Other Utility. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 48
VII. Structure Activity Correlations . . . . . . . . . . . . . . . . . . . . . . . . . . .. 48
VIII. Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 49
Acknowledgements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 51
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 51
Additional References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 61
vi Contents
Steroidal Oligoglycosides and Polyhydroxysteroids from Echinoderms
By L. MINALE, R. RICCIO and F. ZOLLO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 75
1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 76
2. Steroidal Oligoglycosides from Asteroidea (Starfishes): General characteristics .. 77
2.1 Isolation Procedures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 79
3. Asterosaponins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 87
3.1 Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 128
3.1.1 1H and 13C NMR spectra of the steroidal aglycones ........... 128
3.1.2 IH and 13C-NMR spectra of the saccharide chains. . . . . . . . . . .. 133
3.1.3 FAB-Mass spectra ................................ 135
4. Cyclic Steroidal Glycosides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
5. Glycosides of Polyhydroxysteroids. . . . . . . . . . . . . . . . . . . . . . . . . . .. 145
5.1 Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
6. Glycosides of Steroid Phosphates ............................ ' 221
7. Polyhydroxysteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
7.1 Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
8. Steroidal Glycosides and Polyhydroxysteroids from Ophiuroidea (brittle stars). . 252
8.1 Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
9. Assignment of Absolute Configurations to Stereogenic Carbons in the Side
Chain of Polyhydroxysteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
9.1 24-Hydroxysteroids .................................. 264
9.2 26-Hydroxysteroids .................................. 269
9.3 24-Hydroxymethylsteroids .............................. 271
9.4 24-(P-Hydroxyethyl)-and 24-(Carboxymethyl)steroids ............. , 274
9.5 24-Methyl-26-hydroxy-and 24-methyl-26-oic Steroidal side-chains . . . . . . 276
9.6 24-Ethyl-26-hydroxysteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
9.7 24-Methyl-25,26-dihydroxysteroids ......................... 281
Acknowledgements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284
Name Index of Asterosaponins ................................ 285
Molecular Weight Index of Asterosaponins ........................ 286
Name Index of Polyhydroxysteroid, Glycosides. . . . . . . . . . . . . . . . . . . . . . 287
Molecular Weight Index of Polyhydroxy steroid Glycosides .............. 289
Name Index of Polyhydroxysteroids. ........................... , 291
Molecular Weight Index of Polyhydroxysteroids . . . . . . . . . . . . . . . . . . . .. 294
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 297
Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 309
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 322

List of Contribntors
BHAT, Prof. S.V., Department of Chemistry, Indian Institute of Technology, Powai,
Bombay -400 076, India
MINALE, Prof. L., Dipartimento di Chimica delle Sostanze Naturali, Universita degli
Studi di Napoli Frederico II, Via Domenico Monicsano 49, 1-80131 Napoli, Italy.
RICCIO, Dr. R., Dipartimento di Chimica delle Sostanze Naturali, Universita degli Studi
di Napoli Frederico II, Via Domenico Monicsano 49, 1-80131 Napoli, Italy.
ZOLLO, Dr. F., Dipartimento di Chimica delle Sostanze Naturali, Universita degli Studi
di Napoli Frederico II, Via Domenico Monicsano 49, 1-80131 Napoli, Italy.
F orskoIin and Congeners
SUJATA V. BHAT,
Department of Chemistry,
Indian Institute of Technology,
Powai, Bombay, India
Contents
I. Introduction . . . . . . 3
II. Isolation and Structure Determination 4
III. Botanical and Biogenetic Consideration. 7
IV. Chemistry of Forskolin . . . . . . 10
i) Acylation and Alkylation Reactions. 10
ii) Oxidations and Reductions. . . . 15
iii) Biological Oxidations. . . . . . 20
iv) Isomerisation, Fragmentation and Rearrangements 20
V. Synthesis of Forskolin. . . . . . . . . . . 25
i) Approaches to the AB Ring System of Forskolin 25
Intramolecular Diels-Alder (lMDA) Strategy. . 25
Intermolecular Diels-Alder Strategy. . . . . 28
Intramolecular Nitrile Oxide Cycloaddition Approach 30
Intramolecular Radical Mediated Cyc1ization Followed by
Mukaiyama Aldolization. . . . . . . . . . . 30
Intramolecular Michael-Aldol Condensation Strategy. 30
Intramolecular Olefin Cyclization. . . . . . . 33
ii) Approaches to the ABC Ring System of Forskolin. 35
iii) Total Synthesis of Forskolin 36
Ziegler's Approach . 36
Ikegami's Approach . . . 36
Corey's Approach . . . . 37
VI. Biological Activities of Forskolin 43
i) Activation of Adenylate Cyclase 43
ii) Pharmacological Activities with Therapeutic Significance 44
iii) Modulation of Membrane Transport Proteins 46
iv) Effect on Cell Growth 47
v) Other Utility. . . . . . . . . . . . 48
2 SUJATA V. BHAT
VII. Structure Activity Correlations. 48
VIII. Concluding Remarks 49
Acknowledgements 51
References . . . 51
Additional References 61
* Dedicated to Professor Werner Herz on the occasion of his seventysecond birthday.
Forskolin and Congeners 3
I. Introduction
Plants and plant products have been used as drugs for thousands of
years and in recent history have provided a definite stimulus for the
development of natural products chemistry. After the first report on
forskolin (1) (1) in 1977, the last decade has witnessed an increasing
amount of research on the chemistry, synthesis, biochemistry, pharma
cology and various other aspects of the substance in many academic as
well as industrial research laboratories all over the world, leading to a
large number of publications, patents and dissertations.
A number of reviews summarising the chemical, biological, medicinal
potential (2-10) and synthesis (11,12) of forskolin have been reported.
This review will provide a comprehensive survey of the information on
forskolin and congeners available at this time. Forskolin was discovered
as a result of screening programs directed towards the discovery of new
leads from Indian medicinal plants at the Hoechst Research Centre,
III R=H,R,=OAc
I~I R=H,R,=OH
I~l R=R,=H
R
I~I R= H, R,=Me, I~I R =Me,R,=-CH:CH2 1\l.1 R=OH,R,=R2=H
R2=-CH=CH2 lUll R=-CH=CH2 ,R,=Me I~} R=R,=OH,R2=OAc
'II
R=Ac,R,=Me, lUI R=R,=R2=OH
R2=-CH=CH2 lUI R=R,=R2= H
I ~) R = Ac ,R,= -CH=CH2 ' lUI R=R,=OH,R2=H
R2 = Me
Fig. I. Diterpenoids of Coleusforskohlii (/. /6-26)