Vincristine synthetic approaches

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. 

Vinblastine and vincristine have been used clinically for many years. The major importance of vinblastine is as part of a combination treatment for Hodgkin s disease, while vincristine is used in combination chemotherapy of acute lymphoblastic leukemias and lymphomas. Several analogues of the vinca alkaloids have entered clinical use or clinical trials, including vindesine (3), vinorelbine (4), " the naturally occurring anhydrovin-blastine (5), and vinflunine (6). ° Several synthetic approaches to the vinca alkaloids have been developed, especially by Kuehne, while studies of the chemistry of the alkaloids in super acidic media have yielded new alkaloids such as vinflunine. ... 

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