Asymmetric Synthesis of the Indolo[2,3-α]quinolizine Alkaloid (+)-Cuscutamine via a Diastereoselective Intramolecular Pictet-Spengler Reaction

Abstract

A concise total synthesis of Cuscutamine was achieved involving a diastereoselective intramolecular acyl iminium ion mediated Pictet-Spengler reaction. This synthetic strategy provided a direct route to (11S, 13R)-Cuscutamine (2) in only 3 steps with an overall yield of 56 % and an enantiomeric ratio of 88 %. The diastereoselectivity of the reaction is consistent with previous studies that proceed via more highly puckered transition states and the present results thus reveal the importance of the steric contributions to the observed diastereoselectivity.