Total Synthesis of Indole and Dihydroindole Alkaloids. IX Studies on the synthesis of bisindole alkaloids in the vinblastine‐ vincristine series. The biogenetic approach

Abstract

Abstract A detailed study of the reaction of catharanthine N‐oxide and vindoline has been carried out employing various conditions. Under optimum conditions, which involve low temperatures and trifluoroacetic anhydride as reagent, 3′, 4′‐dehydrovinblastine (XIII, R = COOCH 3 ), in reasonable yields is essentially the exclusive product. However two additional products, 18′ ( epi )‐ 3′, 4′‐dehydrovinblastine (XIV, R = COOCH 3 ) and 1′‐hydroxy‐ 3′, 4′‐dehydrovinblastine (XVI, R = COOCH 3 ) are also often isolated. The reaction, which follows the course of a Polonovski ‐type fragmentation process, has been extended to the N‐oxide derivatives of dihydrocatharanthine and decarbomethoxycatharanthine to provide again a series of bisindole alkaloid derivatives, also vinblastines. A mechanistic rationale is provided to explain the various results obtained.