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

183 Pages·1996·4.449 MB·English

by  Dr. A. A. L. Gunatilaka, Prof. Dr. Ch. Tamm, Dr. P. Walser-Volken (auth.), Prof. W. Herz, Prof. G. W. Kirby, Prof. R. E. Moore, Prof. Dr. W. Steglich, Prof. Dr. Ch. Tamm (eds.)

67
Fortschritte der Chemie
organischer Naturstoffe
Progress in the
Chemistry of Organic
Natural Products
Founded by
L. Zechmeister
Edited by
W. Herz, G. W. Kirby,
R. E. Moore, W. Steglich,
and Ch. Tamm
Authors:
A. A. L. Gunatilaka, Ch. Tamm,
P. Walser-Volken
SpringerWienNewYork
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 fur Organische Chemie der Universitat Basel,
Basel, Switzerland
This work is subject to copyright.
All rights are reserved, whether the whole or part of the material is concerned, specifically tho",
of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying
machines or similar means, and storage in data banks.
It) 1996 by Springer-Verlag/Wien
Softcover reprint of the hardcover 1st edition 1996
Library of Congress Catalog Card Number AC 39-1015
Typesetting: Macmillan India Ltd., Bangalore-25
Printed on acid free and chlorine free bleached paper
With 28 Figures and 1 coloured Plate
ISSN 0071-7886
ISBN-13: 978-3-7091-9408-9 e-ISBN-13: 978-3-7091-9406-5
DOl: 10.1007/978-3-7091-9406-5
Contents
List of Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . VII
Triterpenoid Quinonemethides and Related Compounds (Celastroloids).
By A. A. L. GUNATILAKA. .......................... .
1. Introduction ..... 2
2. General Structural Features and Nomenclature 4
3. The Families of Celastroloids ......... . 6
3.1. Quinonemethide Triterpenoids ...... . 6
3.2. 14(15)-Enequinonemethide Triterpenoids . 7
3.3. 9(11)-Enequinonemethide Triterpenoids . 11
3.4. Phenolic and 6-0xophenolic Triterpenoids 14
3.5. 7-0xoquinonemethide Triterpenoids 14
3.6. Dimeric Ce1astroloids .... 15
3.7. Miscellaneous Celastroloids 18
4. Natural Occurrence ....... . 18
4.1. Taxonomic Considerations . 18
4.2. Plant Sources of Celastroloids 19
4.3. Distribution of Natural Celastroloids . 24
4.4. Celastroloids from Tissue Cultures 24
5. Derivatives of Ce1astroloids . . 27
6. The Chemistry of Celastroloids 35
6.1. Isolation Techniques ... . 35
6.2. Structure Elucidation .. . 37
6.2.1. Early Structural Studies of Ce1astrol and Pristimerin 37
6.2.2. Application of Spectroscopic Techniques ... 42
6.2.2.1. UV/VIS and ORD/CD Spectroscopy 42
6.2.2.2. Infrared Spectroscopy. . . . . . . 47
6.2.2.3. NMR Spectroscopy . . ...... . 48
6.2.2.3.1. 1H -NMR Spectroscopy . 49
6.2.2.3.2. 13C-NMR Spectroscopy 59
6.2.2.4. Mass Spectrometry . . 70
6.2.2.5. X-Ray Crystallography .. . 74
6.3. Chemical Reactions ...... . ..... . 76
6.3.1. General Chemical Characterization 76
6.3.2. Degradation and Oxid<\tion .. 76
6.3.3. Reduction and Derivatization .... 79
VI Contents
6.3.4. Addition Reactions 82
6.3.5. Rearrangements . 83
6.3.6. Photochemistry 88
7. Partial Synthesis . . . 89
8. Biosynthetic Aspects 91
9. Biological Activity .. 95
9.1. Antimicrobial Activity. 96
9.2. Antitumor Activity ... 99
9.3. Other Biological Activities 103
10. Conclusions. 103
Addendum .... 105
Acknowledgements . 114
References . . . . . . 114
The Spirostaphylotrichins and Related Microbial Metabolites.
By P. WALSER-VOLKEN and CH. TAMM ............ . 125
1. Introduction . . . . . . . ....... . 125
2. Isolation of Spirostaphylotrichin A (I), B (2), C and D (3/4), Q (5), R (6) and
F (7) from Cultures of Staphylotrichum coccosporum . . . . . . . . . . . . . 127
3. Biosynthetic Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
3.1. Feeding Experiments with 14C_, 13C, and 2H-Labelled Precursors. . 135
3.1.1. Experiments with 14C_ Labelled Precursors. . . . . . 135
3.1.2. Experiments with 13C_ and 2H-Labelled Precursors 136
3.2. Investigation of Mutant Strains and Isolation of Further
Spirostaphylotrichins. . . . . . . . . . . . . . . . . . . . 142
3.2.1. Mutagen Treatment and Selection of Mutants. 142
3.2.2. The Mutant Strain P 84. . 143
3.2.3. The Mutant Strain P 649 . . . . . . . . . . . . . 146
4. Investigation of the Epimerization of Spirostaphylotrichins . 150
5. Discussion of the Results Regarding the Biosynthesis of the
Spirostaphylotrichins. . . . . . . . . . . . . . . . . . . . 153
6. Synthetic Approaches Towards the Spirostaphylotrichins . 156
7. Related Fungal Metabolites: Triticones, Arthropsolides, and Other Compounds 159
7.1. Triticones. . . . . . . . . . . . . . . . . . . 159
7.2. Arthropsolides and Related Compounds 160
References. . . 164
Author Index. 167
Subject Index . 171
List of Contributors
GUNATILAKA, Dr. A. A. L., Department of Chemistry, Virginia Polytechnic Institute and
State University, 3017 Hahn Hall, Blacksburg, Virginia 24061-0212, USA.
TAMM, Prof. Dr. CH., Institut fiir Organische Chemie, Universitiit Basel, St. Johanns-Ring
19, CH-4056 Basel, Switzerland.
WALSER-VOLKEN, Dr. P., Institut fUr Organische Chemie, Universitiit Basel, St. Johanns
Ring 19, CH-4056 Basel, Switzerland.
Triterpenoid Quinonemethides and Related
Compounds (Celastroloids)
A. A. LESLIE GUNATILAKA, Department of Chemistry,
Virginia Polytechnic Institute and State University,
Blacksburg, Virginia, USA
Contents
1. Introduction ........................................ 2
2. General Structural Features and Nomenclature ................... 4
3. The Families of Celastroloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 6
3.1. Quinonemethide Triterpenoids . . . . . . . . . . . . . . . . . . . . . . . . . .. 6
3.2. 14(15)-Enequinonemethide Triterpenoids . . . . . . . . . . . . . . . . . . . .. 7
3.3. 9(1l)-Enequinonemethide Triterpenoids ..................... 11
3.4. Phenolic and 6-0xophenolic Triterpenoids ................... 14
3.5. 7-0xoquinonemethide Triterpenoids ....................... 14
3.6. Dimeric Celastroloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 15
3.7. Miscellaneous Celastroloids ............................ 18
4. Natural Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 18
4.1. Taxonomic Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 18
4.2. Plant Sources of Celastroloids . . . . . . . . . . . . . . . . . . . . . . . . . .. 19
4.3. Distribution of Natural Ce1astroloids . . . . . . . . . . . . . . . . . . . . . .. 24
4.4. Celastroloids from Tissue Cultures ........................ 24
5. Derivatives of Celastroloids ............................... 27
6. The Chemistry of Celastroloids . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 35
6.1. Isolation Techniques. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 35
6.2. Structure Elucidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 37
6.2.1. Early Structural Studies of Celastrol and Pristimerin . . . . . . . . .. 37
6.2.2. Application of Spectroscopic Techniques . . . . . . . . . . . . . . . .. 42
6.2.2.1. UVjVIS and ORDjCD Spectroscopy .............. 42
6.2.2.2. Infrared Spectroscopy. . . . . . . . . . . . . . . . . . . . . . .. 47
6.2.2.3. NMR Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . .. 48
6.2.2.3.1. IH-NMR Spectroscopy. . . . . . . . . . . . . . . .. 49
6.2.2.3.2. 13C_NMR Spectroscopy ................ 59
2 A. A. L. GUNATILAKA
6.2.2.4. Mass Spectrometry . . . . . . . . . . . . . . . . . . . . . . . .. 70
6.2.2.5. X-Ray Crystallography . . . . . . . . . . . . . . . . . . . . . .. 74
6.3. Chemical Reactions ................................. 76
6.3.1. General Chemical Characterization .................... 76
6.3.2. Degradation and Oxidation . . . . . . . . . . . . . . . . . . . . . . . .. 76
6.3.3. Reduction and Derivatization . . . . . . . . . . . . . . . . . . . . . . .. 79
6.3.4. Addition Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 82
6.3.5. Rearrangements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 83
6.3.6. Photochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 88
7. Partial Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 89
8. Biosynthetic Aspects ................................... 91
9. Biological Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 95
9.1. Antimicrobial Activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 96
9.2. Antitumor Activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 99
9.3. Other Biological Activities ............................. 103
10. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Addendum ............................................ 105
Acknowledgements ....................................... 114
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
1. Introduction
The triterpenoid quinonemethides constitute a relatively small group
of unsaturated and oxygenated D:Alriedo-nor-oleananes. In nature these
nor-triterpenoid pigments are found restricted to the higher plant family,
Celastraceae (including Hippocrateaceae; see Sect. 4.1). For this reason,
BRUNING and WAGNER (10) coined the general name "celastroloids" for
this class of compounds, and in this review, this term is used exclusively
for all natural triterpenoid quinonemethides and their structural rela
tives. Celastroloids usually co-occur with other triterpenoid types like
the D:Alriedo-oleananes and lupanes. Despite their structural complex
ity and interesting biological activities, no comprehensive review devoted
specifically to celastroloids has appeared to date. However, mention has
been made of celastroloids in general reviews and handbooks dealing
with other triterpenoid types (1, 26, 108, 123), terpenoids and steroids of
Sri Lankan plants (80), constituents and phytochemistry of Celastraceae
(10, 63, 70, 109), triterpene phenoldienones (110), phenolic triterpenoids
of Sri Lankan Celastraceae (42, 84), and natural quinonemethides (16,
143, 144). Since approximately 70 celastroloids are presently known,
a review devoted entirely to these is now appropriate.
References, pp. 114-123
Triterpenoid Quinonemethides and Related Compounds 3
This review covers the literature included in Chemical Abstracts up
to June 1994 and contains comprehensive discussions on distribution,
structure elucidation, chemistry, biological activity and biosynthetic as
pects of celastroloids. It also includes all their derivatives and related
structures of semisynthetic origin and some unpublished data from our
laboratory and those of others. Some conclusions on current status and
future prospects are drawn at the end.
The discovery of celastroloids and the history of their structure
elucidation demand comment. The discovery of the most common triter
penoid quinonemethides, celastrol (1) and pristimerin (11), and the stud
ies which led to the establishment of their interrelationship will be
considered here whereas the history of their structure elucidation will be
discussed in Sect. 6.2.1.
The powdered roots of Tripterygium wilfordii Hook. f. (family Celas
traceae), called "lei king teng" ("thunder god wine") in Chinese, have been
used in China for centuries as an insecticide. In 1930 the "thunder god
wine" suddenly came into prominence in Chekiang province, China, as
the result of a dispute regarding the damage to valuable and highly
productive valley lands caused by rain water from the nearby hills
following the harvest of Tripterygium roots, which left the soil loose,
hence flooding the valley. The land owners of the valley had requested
that the cultivation of T. wilfordii be forbidden. This quickly provoked
a strong opposition from vegetable growers who complained that they
could not grow their crops without using the powdered roots of T.
wilfordii to kill noxious insects. Entomologists and other experts were
sent to investigate the validity of this claim. As a result of these investiga
tions, CHOU and MEl published the first paper on the root constituents of
Tripterygium wilfordii in 1936 (15). They were able to isolate the insecti
cidal principle (suspected to be an alkaloid) and dulcitol along with an
insecticidally inert pigment named tripterine. Tripterine was later shown
to be identical with celastrol obtained by GISVOLD from another Celas
traceae species, Celastrus scandens (47).
The first scientific paper dealing with celastrol was published in 1939
by GISVOLD who wrote, "One time some investigators thought that the
chief pigment found in the outer bark of the root of Celastrus scandens
was ~-carotene. ~-Carotene is of great importance because of its use as
a standard for vitamin A, and therefore confirmation of its existence in
a plant from which it might be easily isolated and purified was deemed
advisable." However, to his disappointment, the pigment turned out to
be different from ~-carotene. In GISVOLD'S words, "the bark of the root of
Celastrus scandens contains no ~-carotene. A red pigment has been
isolated and named celastrol" (47). GISVOLD was perhaps unaware that
4 A. A. L. GUNATILAKA
BHARGAVA had given the same name to a phytosterol isolated from
Celastrus paniculatus (5).
Tripterygium wilfordii was introduced into the United States from
China in 1941 after its claimed insecticidal activity had been demon
strated (86). In 1942 SCHECHTER and HALLER (132) reisolated from T.
wilfordii tripterine previously reported by Chinese workers and showed
that it was identical with celastrol isolated by GISVOLD. In the early
1950's BHATNAGAR and DIVEKAR (6) were prompted to initiate chemical
studies on an Indian Celastraceae species, Pristimeria indica, as there was
a common belief among the people of North Kanara in India that
a teaspoonful of the paste (obtained by rubbing the root of this plant on
a stone with a little lime juice) administered orally twice a day for 3 days
completely cured respiratory diseases. They were successful in isolating
the antibacterial principle from the root bark of P. indica which sepa
rated as bright orange needles and was named pristimerin. The probable
relationship between pristimerin and celastrol was noted by KULKARNI
and SHAH (102) and later by KAMAT, FERNANDES and BHATNAGAR (98).
However, it was NAKANISHI'S group which firmly established that pris
timerin is the methylated derivative of celastrol (118).
Since the discovery of celastrol (tripterine) and pristimerin and the
establishment of their structural interrelationship, a variety of celas
troloids have been encountered in plants of the family Celastraceae
(including Hippocrateaceae) and these are listed in Tables 1 through 8.
2. General Structural Features and Nomenclature
In general, celastroloids incorporate the 24-nor-D : A-friedo-oleanane
nucleus (Fig. 1) and invariably contain oxygenated functionalities at C-2
2
3
23
Fig. 1. Basic nucleus of celastroloids
References, pp. 114-123