An efficient total synthesis of (+)-entecavir

Abstract

An efficient asymmetric total synthesis of entecavir was accomplished in 9 steps from the commercially available 4-hydroxycyclopent-2-enone (rac-5), representing, to date, the shortest asymmetric total synthesis of this molecule. Key reactions include a lipase-mediated highly efficient kinetic resolution reaction and a highly challenging stereocontrolled copper-catalyzed Michael addition–elimination reaction. This work constitutes a robust basis for the development of a new step-economic and cost-effective process for the production of entecavir.