Synthetic Studies of (+)-Gracilamine Based on Organocatalytic Reaction

Abstract

The Amaryllidaceae alkaloid (+)-gracilamine, isolated from Galanthus gracilis, contains a characteristic pentacyclic ring system with seven consecutive stereogenic centers, including an all-carbon quaternary stereocenter. Recently we have achieved the enantioselective total synthesis of (+)-gracilamine. The synthesis features (i) asymmetric aza-Friedel-Crafts reaction of N-Boc aldimine with sesamol that allowed for constructing the stereocenter at C9a, (ii) a diastereoselective phenolic coupling reaction followed by a regioselective intramolecular aza-Michael reaction to construct the ABCE ring system. This synthesis reveals that the absolute configuration of (+)-gracilamine. Herein, we describe the details of the total synthesis of gracilamine.