Aspidosperma—iboga-type alkaloids catharanthine

It is interesting to note that while vindoline and catharanthine are abundant in Catharan-thus roseus (L.) G. Don, a carbomethoxycleavamine (the initially presumed biogenetic precursor of the binary alkaloids), could not be detected or isolated. This suggested to Atta-ur-Rahman (45) that the VLB-type alkaloids are formed by union of Iboga and Aspidosperma alkaloids, an idea reinforced by biochemical studies (46-49). 

Researches carried out to the early part of 1966 have been comprehensively reviewed and the present account will set out from that point. In brief, the situation reached at that time was as follows. Despite their bewildering variety, three main groups of alkaloids had been recognised (a) the Corynanthe-Strychnos type, e.g. ajmalicine (1) and akuammicine (2) which possess the non-tryptamine unit (3), (b) the Aspidosperma type, e.g. vindoline (4), in which the non-tryptamine unit appears as (5), and (c) the Iboga type, e.g. catharanthine (6), having still a different arrangement of the non-tryptamine unit (7). 

Intrigued by the hypothesis of a dehydrosecodine (120) as a key bioge-netic intermediate in the natural generation of alkaloid structures of both the Aspidosperma (tabersonine, 121) and the Iboga (catharanthine, 21) types (Scheme 33) 108, 109) we developed efficient biomimetic synthe-... 

If the C-15, C-16 bond is oxidatively cleaved, the secodine skeleton results (the proposed progenitor of the Aspidosperma and the iboga systems) through alternative Diels-Alder type cyclizations to afford tabersonine and catharanthine. The bisindole alkaloids of Catharanthus roseus reflect the union of vindoline and catharanthine to afford anhydrovinblastine modification affords the clinically significant alkaloids, vinblastine (VLB) and vincristine (VCR Fig. 39). The alkaloids, particularly VCR, are important as anticancer agents and have led to the development of the semisynthetic derivatives vindesine and vinorelbine (Fig. 40). Synthetic approaches are available to join the monomeric precursors. The enzymatically controlled sequence of reactions from tabersonine to vindoline has been elucidated. 

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