The Alkaloids: Chemistry and Physiology 12

642 Pages·1970·8.2 MB·English

by  R.H.F. Manske (Eds.)

THE ALKALOIDS
Chemistry and Physiology
Edited by
R. H. F. MANSKE
UniRoyal Limited Research Laboratory
Cuelph, Ontario, Canada
VOLUME XI1
1970
ACADEMIC PRESS NEW YORK LONDON
COPYRIGHT0 1970, BY ACADEMIPCR ESSI,N C.
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LIST OF CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors’ contributions begin.
E. G. C. CLARKET, he Royal Veterinary College, University of London,
London, England (513)
L. H. KEITH, Department of Chemistry, The University of Georgia,
Athens, Georgia (xv, 1, 135)
R. H. F. MANSKEU, niRoyal Limited Research Laboratory, Guelph,
Ontario and the University of Waterloo, Waterloo, Ontario, Canada
(455)
S. W. PELLETIEDRep, artment of Chemistry, The University of Georgia,
Athens, Georgia (xv, 1, 135)
F. ~ANTAV+’, Institute of Chemistry, Medical Faculty, Palack$
University, Olomouc, Czechoslovakia (333)
J. E. SAXTONT,h e University, Leeds, England (207)
FRANK L. WARREN, C.S.I.R. Natural Products Research Unit,
University of Cape Town, Rondebosch, Cape Province, South Africa
(245)
V
PREFACE
The proliferation of alkaloid literature which has been so marked for
several decades has continued. The discovery of new sources of known
alkaloids and the discovery of new alkaloids in new and already
examined sources together with new structural and synthetic studies
call for periodic reviews. This volume is an attempt to bring some of
the alkaloid chemistry up-to-date. As in the more recent volumes we
have chosen a number of subjects which seem appropriate at this time.
Entries in the Subject Index are restricted to topics which are basic
to the substances or groups under discussion; incidental mention does
not necessarily merit inclusion. The abbreviations used for journals in
literature references are those found in Chemical Abstracts List of
Periodicals.
Once more the editor, on behalf of the publisher and himself, takes
this opportunity to express his indebtedness to the conscientious and
competent authors who have made the publication of this volume
possible.
R. H. F. MANSKE
Guelph, Ontario
December, 1969
vii
THE DITERPENE ALKALOIDS:
GENERAL INTRODUCTION
S. W. PELLETIERAL.N HD. K EITH
Department of Chemistry,
The University of Georgia,
Athens, Georgia
The diterpene alkaloids are derived from tetracyclic or pentacyclic
diterpenes in which carbon atoms 19 and 20 are linked with the nitrogen
of a molecule of 8-aminoethanol, methylamine, or ethylamine to form a
heterocyclic ring. These alkaloids may be divided into two broad
categories. The first group comprises the highly toxic ester bases (aconi-
tines and lycoctonines) which are heavily substituted by methoxyl and
hydroxyl groups. Hydrolysis of these esters furnishes the relatively non-
toxic amino alcohols (alkamines) which are modeled on a hexacyclic
(319-skeleton. This class of alkaloids is considered in Chapter 1. The
second group includes a series of comparatively simple and relatively
nontoxic alkamines which are modeled on a Czo-skeleton and are treated
in Chapter 2. These compounds (sometimes loosely referred to as the
atisines ") are not extensively oxygenated and contain at most one
"
methoxyl group. One of the distinguishing chemical features of this group
is the formation of phenanthrenes when subjected to selenium or palla-
dium dehydrogenation. A few compounds of this class occur in the plant
as monoesters of acetic or benzoic acid.
Thus far four different types of skeletons* have been encountered
among the diterpene alkaloids. They are the veatchine, atisine, lycoctonine,
and heteratisine types (see chart of skeletons). The veatchine skeleton
which occurs in the Garrya alkaloids, e.g., veatchine, cuauchichicine, and
songorine, incorporates a kaurane skeleton and obeys the isoprene rule.
The atisine skeleton is modeled on an atisane nucleus and differs from the
veatchine type in that ring D is six-memberedrather than five-membered ;
it does not obey the isoprene rule. The atisine skeleton appears in such
alkaloids as atisine, atidine, hetisine, ignavine, and kobusine. The
lycoctonine skeleton, modeled on the aconane framework, is found in one
*
The nomenclature of these alkaloids is based upon the standard skeletons atisane,
kaurane, and aconane with the numbering and stereoohemistry illustrated. These skele-
tons have been incorporated into a proposal for the Common and Systematic Nomen-
clature of Cyclic Diterpenes which will be submitted to the IUPAC Commission on the
Nomenclature of Organic Chemistry in 1969 and published in M. Fetizon and Le-Van-
Thoi's forthcoming book on the cyclic diterpenes.
xvi S. W. PELLETlER AND L. H. KEITH
form or other in most of the aconitines and lycoctonines, e.g., aconitine,
hypaconitine, delphinine, lycoctonine, and ajacine. It may be derived
formally from the atisine skeleton by cleavage of the C-8-C-9 bond,
Veatchine skeleton Kaurane
17 .?
7
8 1 ' ---__
12 *. 18
15 ]OH -----
3 5 7
4 0 6
H
'\
19 18 19 18
Atisine skeleton Atisene
16
15
19 18 19 18
Lycoctonine skeleton Aconane
-
16
Heteratisine skeleton
formation of new bonds between C-7 and C-20 and C-9 and C-15 and loss
of the C-17 exocyclic methylene group. The heteratisine skeleton differs
from the lycoctonine type in that expansion of ring C by insertion of
oxygen has occurred to give a lactone. All the diterpene alkaloids en-
countered to date in nature are constructed on these four skeletal types.
THE DITERPENE ALKALOIDS : GENERAL INTRODUCTION xvii
In certain alkaloids, however, one or more additional ring fusions are
present. Thus, songorine has a bond between C-7 and C-20 of the veatchine
skeleton and kobusine has bonds between C-14 and C-20 and between
C-6 and the nitrogen of the atisine skeleton.
The chemistry of the diterpene alkaloids was last reviewed in a detailed
manner in 1960, with coverage of the literature through the early part of
1957. These chapters survey the literature as listed in Chemical Abstracts
through July 1, 1968.
-CHAPTER 1-
DITERPENE ALKALOIDS FROM
ACONITUM. DELPHlNlUM. AND GARRYA SPECIES:
THE C... DITERPENE AJXALOIDS
S. W . PELLETIEANRD L . H . KEITH
Department of Chemistry.
The Uiiiversity of Georgin.
A the iis. Georgin
I. Introduction ...................................................... 2
I1. Lycoctonine-Type Alkaloids .......................................... 10
A. Lycoctonine(Roy1ine) ............................................ 10
B . Elatine, Anthranoyllycoctonine (Inuline), Ajacine, Methyllycaconitine,
Delsemine, Avadharidine, and Lycaconitine .......................... 16
C . Delpheline, Deltaline (Eldeline, Delphelatine), and Deltamine (Eldelidine) 19
D . Delcosine (Delphamine, Lucaconine, Takao Base I, Alkaloid C), Mono-
acetyldelcosine (Monoacetyllucaconine, Alkaloid B), and 14-Dehydrodel-
cosine (Shimoburo Base 11) ........................................ 26
E . Delsoline ........................................................ 35
F . Browniine and Dehydrobrowniine .................................. 36
I11 . Aconitine-Type Alkaloids ............................................ 40
A . Aconitine ...................................................... 40
B . Jesaconitine .................................................... 58
C . Mesaconitine, Hypaconitine, and Deoxyaconitine ...................... 60
D . Delphinine ...................................................... 64
E . Indaconitine and Pseudaconitine .................................... 12
F. Bikhaconitine ................................................... 78
G . Chasmaconitine and Chasmanthinine ................................ 83
H . Chasmanine (Toroko Base 11). ...................................... 86
I . Homochasmanine ................................................ 93
J . Neoline and Neopelline ............................................ 95
K . Condelphine, Talatizidine, and Isotalatizidine ......................... 99
IV . Lactone-Type Diterpene Alkaloids .................................... 109
A . Heteratisine ..................................................... 109
B . Heterophyllisine, Heterophylline, and Heterophyllidine ................ 115
V. Uncharacterized Alkaloids ........................................... 118
A. Lappaconitine, Talatisine, and Talatisamine .......................... 118
B . Newly Isolated Alkaloids .......................................... 120
References ......................................................... 129
2 S. W. PELLETIER AND L. H. KEITH
I. Introduction
The structures of the more complicated diterpene alkaloids may be
subdivided into two general types of skeletons which are closely related.
TABLE I
ALKALOIDOSF KNOWNST RUCTURE
Alkaloid Correlated with or by- References
-
1. Lycoctonine (royline) By X-ray crystallography 4-6
2. Elatine Lycoctonine 19
3. Anthranoyllycoctonine (inuline) Lycoctonine 19
4. Ajacine Lycoctonine 19
5. Lycaconitine Lycoctonine 19
6. Methyllycaconitine Lycoctonine 19
7. Delsemine Lycoctonine 19
8. Avadharidine Lycoctonine 19
9. Deltaline Delpheline 31
10. Deltaline (eldeline, delphelatine) Delpheline 31
11. Deltamine (eldelidine) Deltaline 36,19
12. Delcosine (delphamine, lucaconine, By X-ray crystallography 64
Takao base I, alkaloid C)
13. Monoacetyldelcosine (alkaloid B, Delcosine 46
monoacetyllucaconine)
14. 14-Dehydrodelcosine Delcosine 54,55
15. De 1 s o1 i ne Delcosine 60
16. Browniine Lycoctonine 69
17. Dehydrobrowniine Browniine 70
18. Aconitine By X-ray crystallography 75, 76
19. Jesaconitine Aconitine 100
20. Deoxyaconitine Aconit ine 113
21. Mesaconitine Aconitine 1
22. Hypaconitine Mesaconitine 112,113
23. Delphinine Aconitine 116
24. Pseudaconitine ( a-pseudaconitine) Aconitine 123
25. Indaconitine Pseudaconitine and delphinine 127
26. Bikhaconitine Pseudaconitine 129
27. Chasmaconitine Bikhaconitine and delphinine 131
28. Chasmanthinine Bikhaconitine 131
29. Chasmanine (Toroko base 11) Browniine 135
30. Homochasmanine Chasmanine 137
31. Neolinea Delphinine (only by ORD) 64e
32. Neopellinea Neoline 140
33. Condelphine - -
34. Isotalatisidine - -
35. Talatisidine -
a Probable structures.
1. THE CIS-DITERPENEA LKALOIDS 3
TABLE I1
ALKALOISDTR UCTURESa
Lycoctonine-ty pe
I
OCH3
OH
Lycoctonine
Elatine
Anthranoyllycoctonine : R = NH2
//O
Ajacine: R = CH&-NH-
9\
3
Lycaconitine: R = -N
VCH3
Methyllycaconitine: R = -N
0
0
11 R0
Avadharidine : Et = -NH-C-CHz-CHz-C-NHz
0 CH3
Dekemine : R = -NH-C-CHII -CHI 2-C-NH2 /O
0 CH3
It 1 /O
or -NH-C-CH2-CH-C-NH2