Enantioselective Total Synthesis of Lycopodine

摘要

The lycopodium family of alkaloids has garnered considerable attention over the years because of their wide-ranging biological activity and structural complexity. The parent member of this family, lycopodine (1), was isolated 125 years ago by Bodeker (Figure 1). Beneficial medicinal properties, such as antipyretic and anticholinesterase activity, have been attributed to lycopodine and other lycopodium alkaloids. To date, seven racemic total syntheses and two racemic formal syntheses of 1 have been reported. Herein, we report the first enantioselective total synthesis of 1. Our retrosynthetic strategy is shown in Figure 1. Key to this strategy is the diastereoselective intramolecular Michael addition of 4 and the Heathcock-inspired Mannich cyclization to form tricycle 2.