Concise and enantioselective total synthesis of (-)-mehranine, (-)-methylenebismehranine, and related Aspidosperma alkaloids.

Abstract

We report an efficient and highly stereoselective strategy for the synthesis of Aspidosperma alkaloids based on the transannular cyclization of a chiral lactam precursor. Three new stereocenters are formed in this key step with excellent diastereoselectivity due to the conformational bias of the cyclization precursor, leading to a versatile pentacyclic intermediate. A subsequent stereoselective epoxidation followed by a mild formamide reduction enabled the first total synthesis of the Aspidosperma alkaloids (-)-mehranine and (+)-(6S,7S)-dihydroxy-N-methylaspidospermidine. A late-stage dimerization of (-)-mehranine mediated by scandium trifluoromethanesulfonate completed the first total synthesis of (-)-methylenebismehranine.