Synthesis and oxidative fragmentation of catharanthine analogs. Comparison to the fragmentation - Coupling of catharanthine and vindoline

摘要

Two new analogs of catharanthine have been synthesized in racemic form. They differ from catharanthine in the fusion of the indole ring to the non-aromatic portion of die iboga skeleton, with the [2,3] fusion present in catharanthine being replaced by [2,1] and [3,2] fusions. The corresponding deethyl analogs were also prepared and methodological improvements were applied to an existing synthesis of deethylcatharanthine and a formal synthesis of racemic catharanthine. The reactivity of the catharanthine analogs toward coupling with vindoline was examined. Coupling was attempted by both die amine oxide fragmentation (Potier) and Fe3+ methods. Under Potier conditions the [2,1] fused analogs give low yields of coupling products in which vindoline is attached to the 3-position of the indole ring. The [3,2] isomers undergo fragmentation of the C16-C21 bond, as observed for catharanthine, but no coupling to vindoline occurs. The reactivity, oxidation potentials and conformation of the analogs are compared with catharanthine, deethylcatharanthine and N-methylcatharanthine. (C) 1998 Elsevier Science Ltd. All rights reserved. [References: 53]