The Alkaloids: Chemistry and Physiology 14

607 Pages·1973·7.61 MB·English

by  R.H.F. Manske (Eds.)

THE ALKALOIDS
Chemistry and Physiology
Edited by
R. H. F. MANSKE
Department of Chemistry, University of Waterloo
Waterloo, Ontario, Canada
VOLUME XIV
1973
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LIST OF CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors’ contributions begin.
JASJIST. B INDRAM, edical Research Laboratories, Pfizer, Inc., Groton,
Connecticut (84)
R. L. CASTENSOND, epartment of Chemistry, The Pennsylvania State
University, University Park, Pennsylvania (226)
G. GRETHEC, hemical Research Department, Hoffmann-La Roche, Inc.,
Nutley, New Jersey (181)
S. R. JOHNDSiv, ision of Applied Chemistry, C.S.I.R.O., Melbourne,
Australia (325)
TETSUJI KAMETANPI,h armaceutical Institute, Tohoku University,
Aobajama, Sendai, Japan (265)
MASUO KOIZUMI, Pharmaceutical Institute, Tohoku University,
Aobajama, Sendai, Japan (265)
J. A. LAMBERTODNi,v ision of Applied Chemistry, C.S.I.R.O., Mel-
bourne, Australia (325)
D. B. MACLEANM, cMaster University, Hamilton, Ontario, Canada (348)
R. H. F. MANSKE,D epartment of Chemistry, University of Waterloo,
Waterloo, Ontario, Canada (508)
RUSSELLR ODRIGOW, aterloo Lutheran University, Waterloo, Ontario,
Canada (407)
J. E. SAXTONT,h e University, Leeds, England (123)
MAURICES HAMMAD,e partment of Chemistry, The Pennsylvania State
University, University Park, Pennsylvania (226)
V. SNIECKUSU, niversity of Waterloo, Waterloo, Ontario, Canada (325)
J. TOMKOD, epartment of Pharmacognosy, Pharmaceutical Faculty,
Comenius University, Bratislava, Czechoslovakia (1)
M. R. USKOKOVICC, hemical Research Department, Hoffmann-La
Roche, Inc., Nutley, New Jersey (181)
Z. VOTICKP,I nstitute of Chemistry, Slovak Academy of Sciences,
Bratislava, Czechoslovakia (1)
ix
PREFACE
The editor, the publishers, and particularly the authors of previous
volumes in this treatise are pleased with the reception accorded their
efforts. Since there has been no abatement in the flood of publications
dealing with alkaloids we have the temerity to add another review.
There are times when we would welcome more information than is
accessible to us, so this is another invitation to authors to supply us with
reprints.
R. H. F. MANSKE
xi
-CHAPTER 1-
STEROID ALKALOIDS: THE VERATRUM AND BUXUS
GROUPS
J. TOMKOA*N D Z. VOTICK%
Institute of Chemistry
Slovak Academy of Sciences, Bratislava, Czechoslovakia
I. Introduction.. 1
Alkaloids ........................................................... 5
A. The Jervanine and Veratranine Subgroup .......... .. 5
B. The Cevanine Subgroup .......................................... 17
C. The Solanidanine Subgroup. ....................... ............ 19
D. The 22,26-Epiminocholestane Subgroup ............ ............ 20
E. Other Alkaloids .................................................. 24
111. Structures and Chemical and Physicochemical Properties of Buxus Alkaloids 32
A. Dibasic Buxus Alkaloids .......................... 32
B. Monohasic Buxus Alkaloids. ....................................... 58
C. Alkaloids of Unknown Structure ................................... 67
D. Syntheses in the Buxus Alkaloids ............... 68
IV. Biosynthetic Notes ................................................. 78
References ....... ..... ........... 79
I. Introduction
Reviews of the chemistry of Veratrum alkaloids have been written
by Kupchan and By (1)a nd of Buxus alkaloids by Cernf and Sorm (2).
In addition to the recently published results in the chemistry of plant
steroids (3), steroidal and abnormal steroidal alkaloids have been
reviewed by Sat0 and Brown (4).G outarel(5)h as summarized the latest
advances among Buxus alkaloids. Some physicochemical and other
data of Veratrum and Buxus alkaloids are given in the monograph by
Raffauf (6).T he progress in the Veratrum and Buxus alkaloids since
the appearance of Volumes IX and X of this series is summarized in
this chapter.
*and Department of Pharmacognosy, Pharmaceutical Faculty, Comenius University,
Bratislava.
2 J. TOMKO AND z. VOTICKP
In agreement with the IUPAC Corrected Tentative Rules (7) for
Steroid Nomenclature the Veratrum alkaloids are classified in the
jervanine (l)v, eratranine (2), cevanine (3),a nd solanidanine (4) groups.
18 21
>H H CH3H PH3 H CH3H FH3
H3C 14 16 0 23 25 H3C HH
15 24
2 lOh8 H' H 2C7H 3 H H
s 5 7
4 , 6
H H
1 (22S,23R,25S)-5a-Jervanine 2 (22R,25S)-5a-Veratranine
27
H
3 (22S,25S)-5a-Cevanine
Veralkamine and veralinine are regarded as derivatives of the rearranged
steroid hydrocarbon cholestane (5). However, there are also alkaloids
possessing a normal cholestane skeleton (the 22,26-epiminocholestanes;
cf. Vol. X, p. 60).
The alkaloid veramine could be considered a derivative of rearranged
tomatanine (6) (Z).*
* Semisystematic names proposed by the IUPAC Committee for nomenclature could
well be applied to Veratrum alkaloids with the exception of veramine. The (3-16 hydro-
gen in veramine is 8-oriented,w hereas the side chaia at C-17 is a-oriented; hence tomata-
nine, which has a C-16 a-a nd a C-17 a-hydrogen, could not be taken for the fundamental
skeleton. Some other Veratrum alkaloids (e.g., veralkamine, veralinine) having the C-17
side chain a-oriented are entered among the (2-17 8-methyl-18-nor-epiminocholestanes.
To demonstrate the stereochemistry in the side chain we have applied the common
graphic signs accepted in organic chemistry.
1. STEROID ALKALOIDS 3
Attempts have been made to classify Buxus alkaloids according to
various features. Thus cycloartenol (7)a nd cycloeucalenol (8) were
proposed to be the fundamental skeletons characterizing two groups
of Buxus alkaloids (7a).A nother proposal was to divide Buxus alkaloids
into cyclo-9/?,19- (9) and 9(10 +- 19)deo-pregnane (10) groups (8),
or to classify them according to various substitution patterns (9-11).
It seems, however, reasonable to distinguish Buxus alkaloids according
to the number of nitrogen atoms incorporated. The letter suffixes A
H
4 (22S,25S)-5&01anidanine 5 5a-Cholestane
H
6 (22S,25S)-5a-Tomatanine
to P (Table I), indicating the number of methyl groups attached to
nitrogen atom or atoms (12), offer a further subdivision of Buxus
alkaloids. This classification has been used throughout this chapter.
The designation of Buxus alkaloids shown in Table I is, however,
not based on general principles of organic chemical nomenclature;
it is somewhat inconvenient to memorize; and it refers only to the methyl
substitution on nitrogen. Nonetheless, the creation of new semisystem-
atic names for all possible Buxus alkaloids would complicate still
more the nomenclature hitherto used. Since Buxus alkaloids have the
4 J. TOMKO AND z. VOTICK~
fundamental pregnane skeleton, it seems reasonable to designate them
as derivatives thereof, applying the recommended IUPAC rules (7):
for example, buxamine-A (139) = 3P,20a-bis(dimethylamino)-4,4,14a-
trimethyl-9( 10 -+ 19)-abeo-5a-pregna-91( l ),lO-diene; buxarine-F (209) =
16a-hydroxy-3P-b enzamido-20a- dimethylamino - 4,4,14a- trimethyl-9P,
7 Cycloartenol 8 Cycloeucalenol
H
9 9~,19-Cyclo-5a-pregnane
H
10 g(10 19)-abeo-5a-Pregnane
--f
19-cyclo-5a-pregnan-l l-one; trans-cyclosuffrobuxinine-M (262) = trans-
3~-methylamino-4-methylene-l4a-methyl1-9-9c~y,c lo- 5a-pregn - 17 -en -
16-one; etc.
1. STEROID ALKALOIDS 5
TABLE I
EXTENDEDN OMENCLATUORFE Buxus ALKALOIDS
R1 R3
/ /
C-3 N (3-20 N
suffix R1 R2 R3 R4
Dibasic alkaloids
A CH3
B CH3
C H
D H
E CH3
F H
G CH3
H H
I H
Monobasic alkaloids
K CH3
L -
M CH3
N -
0 H
P -
11. Structures and Chemical and Physicochemical Properties
of Veratrum Alkaloids
A. THE JERVANAINNDE V ERATRANINES UBGROUP
In accordance with the nomenclature in this chapter the alkaloids
veratrobasine, jervine, 1l -deoxojervine (identical with cyclopamine),
veratramine, verarine and the glycoalkaloids veratrosine, pseudo-
jervine, and cycloposine belong to the bases of jervanine and veratra-
nine type.
1. Veratrobasine
The empirical formula of veratrobasine (11) isolated from Veratrum
album L. (13,14)w as revised and the structure, including the stereo-
chemistry, determined by means of X-ray diffraction analysis (15).
6 J. TOMKO AND z. VOTICKP
On the basis of this result the alkaloid is identical with ll-hydroxy-
jervine [(22S,2 3R, 25S)-jerva-5,12-dienine-31PI7p -diol] (11).
The determination of the structure of veratrobasine definitely settled
the discrepancies in the structure of the related bases, the jervanine
and veratranine subgroup and particularly of jervine.
R R'
H 11 H H
12 CH,CO NO
H H 13 CH,CO H
16 CpH5CO NO
RO 17 CEH~COH
The photolysis of 11-nitrite esters of veratrobasine was studied by
Suginome et al. (16). Thus, with nitrosyl chloride in pyridine, 3-0,N-
diacetylveratrobasine (13) afforded the corresponding stable nitrite
12, which was photolyzed. The starting material 12, the 19-oximino
derivative 14, and the substance of assignable structure 15 were
isolated from this reaction. The photolysis of 3-0,N-dibenzoylveratro-
basine-1 1-nitrite (16) led to 3-0,N-dibenzoylveratrobasine (17) and
the compound formulated as 19-nitro-N,O-dibenzoylveratrobasine
(18).
H
RO
R R2
R1
14 H CH,CO CH=NOH
18 CEHSCO CEHSCO CHZNOZ
,,HH TOCH,
H ; \H H
HO
15