Bisindole alkaloid, biosynthesis

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... 

ISOLATION, STRUCTURE ELUCIDATION, AND BIOSYNTHESIS OF THE BISINDOLE ALKALOIDS OF CATHARANTHUS... 

Additionally, there had, for many years, been a vast synthetic effort underway aimed at the synthesis of the two monomeric units, where it was anticipated that the two units could be joined to form the vinblastine-type bisindole alkaloids. Coincidentally, as it transpired, 20 years of effort in the areas of synthesis and biosynthesis converged, at almost the same time, on the compound 3, 4 -anhydrovinblastine (8). 

This review of the biosynthesis of the bisindole alkaloids of C. roseus is organized along a developing biosynthetic pathway, as far as possible, and relies on the notion that the most sophisticated studies are those utilizing the purified enzyme systems. Biosynthetic studies on the other monoterpene indole alkaloids are not reviewed here. 

Although ajmalicine (39) is not on the pathway to the bisindole alkaloids, it is a compound of substantial commercial interest, and several of the intermediates in its formation are probable intermediates in the extended biosynthetic pathway. This work is therefore reviewed for the purpose of completeness of studies on C. roseus. Considerable progress has been made on the biosynthesis of ajmalicine (39), and the studies on the formation of strictosidine (33) and cathenamine (76) have already been described. One of the preparations described by Scott and Lee was a supernatant from a suspension of young seedlings of C. roseus which af-... 

The only study of the biosynthesis of bisindole alkaloids in intact plants using advanced precursors was reported by Scott and co-workers in 1978... 

Higher plants are a very important source of medicinally useful compounds. Catharanthus roseus is one of the most important of these plants, and this chapter focuses on the further isolation work directed at the identification of new potentially more active and/or less toxic bisindole alkaloids. In addition, the biosynthesis of the indole alkaloids of C. roseus is reviewed. While the former area of research has been dominated by sophisticated high-field NMR and high-resolution mass spectral analyses. 

Kutney JP (1990) Biosynthesis and synthesis of indole and bisindole alkaloids in plant cell cultures a personal overview. Nat Prod Rep 7, 85-103. 

The first volume in this series was, perhaps, sui generis, in that it comprised reviews of developments in alkaloid chemistry over an eighteen-month period instead of the twelve-month period adopted for subsequent Reports. There was also included sufficient background material to enable the new work to be placed in perspective in its own particular area, as well as three summaries of a more extended kind these were concerned with the biosynthesis of the terpenoid indole alkaloids, the bisindole alkaloids, and alkaloids of current pharmacological or clinical interest. 

Bisindole alkaloids of Catharanthus C-20 position as a functional hot spot in, 37, 133 (1990) isolation, structure elucidation and biosynthesis, 37,1 (1990) medicinal chemistry of, 37,145 (1990)... 

Martin GE, Zektzer AS (1988) Long-range two-dimensionalear heteronuclear chemical shift correlation. Magn Reson Chem 26 631-652 Massiot G, Nuzillard JM, Richard B, Le Men-Olivier L (1990) Alternative partial synthesis of bisindole alkaloids. Tetrahedron Lett 31 2883-2884 Meksuriyen D, Cordell GA (1988) Biosynthesis of staurosporine. 1. and C NMR assingments. J Nat Prod 51 884-892... 

Stuart, K. L., J. P. Kutney, T. Honda, and B. R. Worth, Studies on the biosynthesis of bisindole alkaloids. The final stages in biosynthesis of vinblastine, leurosine, and Catharine, Heterocycles, 9, 1391-1395 (1978). 

Investigation of the biosynthesis of the bisindole alkaloid, vinblastine (6.270) has shown that it does, as expected, arise from catharanthine (6.239) and vindoline (6.244) probably by the mechanism shown in (6.269) [188, 189]. 

Since the last major review of the biosynthesis of the monoterpenoid indole alkaloids (97), there have been several full and partial 98-104) reviews of various aspects of the work that has been conducted since 1974. Two major developments have dominated the field in this period, namely, the demonstrations that (i) strictosidine (33) is the universal precursor of the monoterpenoid indole alkaloids and (ii) selected cell-free systems of C. roseus have the ability to produce the full range of alkaloid structure types, including the bisindoles. This section traces some aspects of these developments, paying particular attention to work been carried out with C. roseus, and omitting work, important though it may be, on other monoterpenoid indole alkaloid-producing plants, e.g., Rauwolfia, Campto-theca, and Cinchona. 

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