Synthetic entry into yohimbinoid alkaloids and novel synthesis of (±)-17-methoxy-hexadehydroyohimbane

Abstract

A novel method has been developed for the synthesis of (±)-17-methoxy-hexadehydroyonimbane (11̲) which could be converted to yohimbinoid alkaloids through a sequence of reactions. The approach for the desired synthesis was based on the choice of 6-methoxy-3-isochromanone (9̲) as a suitable synthon for the construction 9̲ of non-nitrogeneous moiety. The nitrogeneous portion was developed from tryptamine. An appropriate condensation of 9̲ and tryptamine yielded (±)-17-methoxy-hexadehydroyohimbane. 6-Methoxy-3-isochromanone (9̲) which is a δ-lactone was prepared from 5-methoxy-2-indanone (3̲) by Baeyer-Villiger oxidation. A simple procedure for the synthesis of 3̲ has been developed by a unique acid catalysed diazoketone cyclisation. It deserves mention in this connection that the acid catalyzed cyclization was facile with 3-methoxy-benzyl diazomethyl ketone (8̲ ) but 4-methoxybenzyl diazomethyl ketone (2̲) was reluctant to cyclize. All attempts in this direction resulted in the formation of a hydroxy ketone (4̲) as a major product.