Specialist Periodical Reports provide systematic and detailed review coverage of progress in the major areas of chemical research. Written by experts in their specialist fields the series creates a unique service for the active research chemist, supplying regular critical in-depth accounts of progress in particular areas of chemistry. For over 80 years the Royal Society of Chemistry and its predecessor, the Chemical Society, have been publishing reports charting developments in chemistry, which originally took the form of Annual Reports. However, by 1967 the whole spectrum of chemistry could no longer be contained within one volume and the series Specialist Periodical Reports was born. The Annual Reports themselves still existed but were divided into two, and subsequently three, volumes covering Inorganic, Organic and Physical Chemistry. For more general coverage of the highlights in chemistry they remain a 'must'. Since that time the SPR series has altered according to the fluctuating degree of activity in various fields of chemistry. Some titles have remained unchanged, while others have altered their emphasis along with their titles; some have been combined under a new name whereas others have had to be discontinued.
The Alkaloids Volume 5
A Review of the Literature Published Between July 1973 and June 1974
By J. E. SaxtonThe Royal Society of Chemistry
Copyright © 1975 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-297-2Contents
Chapter 1 Biosynthesis By R. B. Herbert, 1,
Chapter 2 Pyrrolidine, Piperidine, and Pyridine Alkaloids By V. A. Snieckus, 56,
Chapter 3 Tropane Alkaloids By J. E. Saxton, 69,
Chapter 4 The Pyrrolizidine Alkaloids By J. E. Saxton, 77,
Chapter 5 Indolizidine Alkaloids By J. E. Saxton, 87,
Chapter 6 The Quinolizidine Alkaloids By J. E. Saxton, 93,
Chapter 7 Quinoline, Quinazoline, Acridone, and Related Alkaloids By V. A. Snieckus, 103,
Chapter 8 β-Phenethylamines and the Isoquinoline Alkaloids By H. O. Bernhard and V. A. Snieckus, 111,
Chapter 9 Amaryllidaceae and Related Alkaloids By V. A. Snieckus, 170,
Chapter 10 Erythrina and Related Alkaloids By V. A. Snieckus, 176,
Chapter 11 Indole Alkaloids By J. A. Joule, 183,
Chapter 12 Lycopodium Alkaloids By V. A. Snieckus, 228,
Chapter 13 The Diterpenoid Alkaloids: Chemistry and Synthesis By S. W. Pelletier and S. W. Page, 230,
Chapter 14 Steroidal Alkaloids of the Apocynaceae, Buxaceae, Asclepiadaceae, and of the Salamandra–Phyllobates Group By F. Khuong-Huu and R. Goutarel, 242,
Chapter 15 Solanum and Veratrum Steroidal Alkaloids By R. B. Herbert, 256,
Chapter 16 Miscellaneous Alkaloids By V. A. Snieckus, 265,
Author Index, 291,
CHAPTER 1
Biosynthesis
BY R. B. HERBERT
'Being very anxious to find by experiment some support for this still purely speculative view....'
'It was completely unforeseen and opens to physiology new horizons, distant, but sure'
L. Pasteur
1 Introduction
As this is the fifth of these Reports the Reporter is prompted to look back over the past five years in an attempt to recall the important developments of the period. There has of course been a prodigious amount of experimental work and it can be said fairly accurately that the gross topography of the biosynthesis of almost all the plant bases is now known. In a general sense, and rising out of consideration of the detail of biosynthetic pathways, it is the tracing of the stereochemistry of the biological processes which has proved the most fascinating and stimulating both from an intellectual and from an experimental point of view. As a worthwhile consequence more effort is being expended in attempts to understand the enzymic processes involved in biosynthetic processes. In a different direction a recent development has been the harnessing of plants for the synthesis of unnatural alkaloids. At its most sophisticated this can also provide information on enzyme function.
The major siege that was laid against the redoubtable problem of the biosynthesis of a large group of indole alkaloids, represented by ajmalicine (1), akuammicine (2), and catharanthine (3), had been raised by the beginning of the quinquennium with the discovery that the non-indolic C9-C10 unit of each (indicated by heavy bonding) had a common terpenoid origin and that loganin (4) is a key intermediate. More information followed, and related pathways to the Cinchona and Ipecac alkaloids were delineated. Yet there remains fascinating detail to be uncovered.
The solution to the enigma of the biosynthesis of colchicine (5) is of longer standing. More details on the unexpected but simple pathway to this non-basic alkaloid have come with the publication of full papers.
In the light of established pathways to aporphine alkaloids (see p. 15) study of the biosynthesis of glaucine (6) and related bases in Dicentra eximia might have been expected to yield orthodox results. On the contrary, however, a novel pathway was unearthed which implicates dienone intermediates of quite unexpected structure: (7)/(8) for glaucine (6). There is good evidence that the dienone (7) is also involved in the elaboration of the Erythrina alkaloids, along a pathway which has several remarkable features.
Hidden in the old literature was the solution to the long-standing problem of the biosynthesis of the C2 unit (C-1 and C-9) of anhalonidine (12) and the C1 unit (C-1) of anhalamine (13). Only recently was the original suggestion for the biosynthesis of these cactus alkaloids examined, with positive results. Thus the two acids (10) and (11) were found to be precursors for (12) and (13) respectively. They apparently derive in turn from the phenethylamine (9) and pyruvic acid or glyoxylic acid. Attention should be drawn at this point to the very detailed mapping of phenethylamine biosynthesis in cactus species.
Much was already kndwn of the gross features of Amaryllidaceae alkaloid biosynthesis five years ago and in the ensuing period it has been the revelation of the intricate stereochemistry of the processes involved which has proved most interesting. Newer aspects of this work are discussed in this Report (p. 19).
Structural relationships are not always what they seem: it has recently been demonstrated that the mesembrine alkaloids, superficially related to those of the Amaryllidaceae, arise by a quite different pathway, albeit from the same amino-acids (see p. 22).
Research on the biosynthesis of piperidine alkaloids has been consistently stimulating and interesting. There has been a most successful marriage of hypothesis and experiment which can be traced back over the past five years. As a result of the detailed and sophisticated studies elegant theory now stands on a firm experimental base. In particular, it is the fates of individual tritium and carbon atoms in the conversion of lysine into these alkaloids which has allowed the development of the pathway as it now stands (see p. 5). Of significance here is the demonstration that L-lysine is the preferred progenitor of piperidine alkaloids whereas the D-isomer is converted into pipecolic acid in the same plant (see p. 7).
In this area the biosynthesis of the Lycopodium alkaloids, e.g. lycopodine (14) and cernuine (15), is of further interest. Lycopodine and cernuine were considered to be modified dimers of pelletierine (16) because two intact molecules of precursors like lysine and Δ1-piperideine were used for the construction of a single molecule of the alkaloids. Paradoxically, however, pelletierine (16) only gives rise to one of two C8N units (heavy bonding) of (14) and (15). It is now clear that pelletierine is an obligatory intermediate in lycopodine biosynthesis and a satisfying explanation has been advanced to account for the paradox.
Although structurally very similar to pelletierine (16) the hemlock alkaloid coniine (17) is notably of quite different origins, arising as it does from acetate in a fairly well understood pathway.
The biosynthesis of alkaloids containing a pyrrolidine ring such as hyoscyamine (18) and hygrine (19) is similar to the biosynthesis of those with a piperidine nucleus only in so far as the alkaloids arise from homologous amino-acids. The notable difference is that early N-methylation (of ornithine) is apparently an important reaction in the elaboration of pyrrolidine alkaloids, whereas N -methylation occurs late in the formation of the piperidine bases.
There has been a steady progress in the fitting together of the pieces that make up the pattern of furoquinoline and ergot alkaloid biosynthesis so that the pathways for each of these groups is now fairly clear. Both have been the subject of...
