Enantioselective Formal Synthesis of (-)-Catharanthine through Enzyme-Catalyzed Desymmetrization of a meso -Azabicyclo [2.2.2]octane

Iboga-type indole alkaloids are a promising compound group of potentially effective drugs. The common indole-fused pentacyclic skeleton is composed of an isoquinuclidine, and both enantiomers of this architecture are naturally present. In this study, we used enzymatic desymmetrization to obtain an optically active isoquinuclidine possessing four chiral carbon centers from a prochiral diester in one step. In addition, we synthesized a pentacyclic intermediate for catharanthine in an enantioenriched form through the late-stage construction of the common Iboga scaffold.

Automated summary

In this study, an optically active isoquinuclidine with four chiral carbon centers was obtained using enzymatic desymmetrization. Additionally, a pentacyclic intermediate for catharanthine was synthesized in an enantioenriched form through late-stage construction of the common Iboga scaffold.