Anodic C16–C21 fragmentation of catharanthine in methanol. Synthesis of 16-methoxycleavamine

Abstract

Two-electron controlled potential oxidation of catharanthine (Cath) affords 2 in 65% yield. Compound 2 is reduced to 16-methoxycleavamine in 95% yield. Cyclic voltammetry experiments show that catharanthine hydrochloride (CathH⁺) in methanol solution in the presence of 2,6-lutidine exists in acid–base equilibrium with Cath as a free base which is oxidized at 0.7 V vs. SCE. Oxidation of Cath to Cath˙⁺ and fragmentation of the C16–C21 bond is assumed to occur via a concerted mechanism.