Alkaloid chemistry

Key words alkaloids, enzymes, genes, intermedia, metabolism, models, pathways, precursors, skeleton, synthesis 

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A major trend in organic synthesis, however, is the move towards complex systems. It may happen that one needs to combine a steroid and a sugar molecule, a porphyrin and a carotenoid, a penicillin and a peptide. Also the specialists in a field have developed reactions and concepts that may, with or without modifications, be applied in other fields. If one needs to protect an amino group in a steroid, it is advisable not only to search the steroid literature but also to look into publications on peptide synthesis. In the synthesis of corrin chromophores with chiral centres, special knowledge of steroid, porphyrin, and alkaloid chemistry has been very helpful (R.B. Woodward, 1967 A. Eschenmoser, 1970). 

Carbon-oxygen bonds are formed by the Ullmann reaction (- coupling of aryl halides with copper) which has been varied in alkaloid chemistry to produce diaryl ethers instead of biaryls. This is achieved by the use of CuO in basic media (T. Kametani, 1969 R.W. Dos-kotch, 1971). 

The enamine-imine tautomerism of the indolenine system gives rise to rearrangement reactions of interest in indole alkaloid chemistry. Thus the synthesis of dihydroburnamicine (625) utilized the rearrangement of an acetoxyindolenine to an a-hydroxyalkyl indole, presumably through an intermediate enamine. Similarly 2,3-dialkyl indoles undergo oxidations to 2-acyl indoles (626-631). 

It is not proposed to discuss these topics, which have been adequately reviewed elsewhere, but to focus attention on general aspects of carboline chemistry, including relevant findings which emerged incidentally in the course of degradative and synthetic work in the field of indole alkaloid chemistry. The only published review on the carbolines emphasizes aspects of the work carried out prior to 1950. 

The Hofmann-Loeffler-Freytag reaction has been described with A-chloro-as well as A-bromoamines—the former however usually give better yields. A-chlorinated primary amines react well in the presence of Fe-(II) ions. Just like the Barton reaction, the Hofmann-Loeffler-Freytag reaction has been applied mainly in steroid chemistry. An interesting example from alkaloid chemistry is the synthesis of nicotine 12 by Loeffler ... 

A recent report from the U.S. National Academy of Sciences estimates than less than 1% of all living species have been characterized. Thus, alkaloid chemistry remains today an active area of research, and innumerable substances with potentially useful properties remain to be discovered. 

This product has been used to make (17) and (18), both intermediates in indole alkaloid chemistry. How might (13) be converted into (17) and (18) ... 

An international team of experts review the whole field of alkaloid chemistry This volume contains three special non recurrent reviews on bisindole alkaloids, the biosynthesis of terpertoid indole alkaloids, and on pharma -cologicalty interesting ar>d chemically useful alkaloids it covers the period January 1969 to Jur>e 1970. 50Spp til 00... 

Hesse, M. Alkaloid Chemistry, Wiley Interscience, New York, 1978. 

M. Shamma, The Isoquinoline Alkaloids Chemistry and Pharmacology , Academic Press, New York, 1972. 

G. E. Martin, M. Solntseva and A. J. Williams, Applications of 15N NMR spectroscopy in alkaloid chemistry, in Modern Alkaloids Structure, Isolation, Synthesis and Biology, E. Fattorusso and O. Taglialatela-Scafati (eds.), Wiley, New York, 2008, pp. 409-476. 

Other reviews related to this contribution should also be mentioned, in addition to the chapters of this series, which we shall recall later. Some of these deal in general with the problem of classification of indole alkaloids and with chemo-taxonomic investigation (7-5). The chemistry of indole alkaloids is included in the Royal Society of Chemistry s Specialist Periodical Reports and has been extensively reviewed in a one-volume survey edited by J. E. Saxton (6), presenting a reasonably complete, although not exhaustive, picture of the state of the art. Other books on indole alkaloid chemistry treating this area cursorily should also be mentioned (7, 8). Recently, the genus Tabernaemontana was excellently reviewed, particularly with respect to taxonomy, phytochemistry, ethnobotany, and pharmacology (9). 

It should be mentioned that during the last 13 years the Royal Chemical Society published 13 volumes of Special Periodical Reports on Alkaloids (7), which in very brief form reconsidered the publications on alkaloid chemistry and biochemistry that appeared in the preceding years. Recently, this reviewing has been continued in Natural Product Reports. 

Finer-Moore, J., Arnold, E. and Clardy, J. (1984). Alkaloids Chemistry Biological Perspectives (ed. Pelletier, S.W.), Vol. 2, p. 2. Wiley-Interscience, New York... 

Marion, L. The Indole Alkaloids, in The Alkaloids, Chemistry and Physiology Vol. II. New York Academic Press 1952. 

Fodor, G.B. and Colasanti, B. (1985). The pyridine and piperidine alkaloids chemistry and pharmacology, in Pelletier S., Ed., Alkaloids chemical and biological perspectives, Vol. 3, John Wiley and Sons, New York, pp. 3-91. 

Many indole alkaloids are formed in vivo from L-Trp and its derivatives. The Pictet-Spengler reaction of L-Trp with aldehydes follows the biosynthetic route and is therefore one of the most important synthetic methods in alkaloid chemistry (50OR151). A variety of aldehydes have been used for these purposes, from formaldehyde and acetaldehyde to other, more complex aldehydes [36JBC(113)759 41JCS153 48JA219 59BSF1866 ... 

The almost simultaneous discovery of vinblastine (1) by Noble et al. (57) and by Svoboda and co-workers (58) is one of the the most publicized events in alkaloid chemistry. Since its initial discovery, vinblastine (1) has been reisolated from C. roseus several times (47 9,57-60,) and it has also obtained from C. ovalis (32), C. longifolius (33), and C. trichophyllus (60). The large-scale separation of vinblastine (1) and vincristine (2) from C. roseus received attention from pharmaceutical industries, and several procedures for the separation of these alkaloids have been reported in the patent literature (61-71). 

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