Synthetic Exploration and Divergent Total Synthesis of Tacaman Monoterpenoid Indole Alkaloids.

Abstract

Based on the key intermediate successfully applied in our previous research on the synthesis of monoterpenoid indole alkaloids, an efficient divergent total synthetic route for Tacaman alkaloids has been developed in this work. The key transformations of this route mainly include: a formal 1,2-migration reaction mediated by a cyclopropane intermediate, an umpolung-promoted retro-aza-Michael reaction followed by amidation, as well as a regioselectively controllable formal hydration reaction of trisubstituted double bonds. Via this efficient divergent strategy, the total synthesis of tacamonine, tabercamine K and 19S-hydroxyapotacamine, as well as the formal synthesis of descarbomethoxy-tacamine and 17-β-hydroxy-tacamonine, have been successfully achieved.