Synthesis of (R)- and (S)-4-Hydroxy-2-cyclopenten-1-ones: Total Synthesis of Entecavir, Abacavir, and Carbovir

Abstract

A new synthetic procedure was developed for the chiral synthons (R)-1b and (S)-1b that enabled us to complete the asymmetric total synthesis of entecavir, abacavir, and carbovir. This lipase-based procedure holds good potential for developing a green process for the industrial production of (R)-1b and (S)-1b with a high enantiomeric purity. The asymmetric synthesis of entecavir was powered by the highly challenging Michael addition–elimination reaction. The asymmetric synthesis of abacavir and carbovir was featured by the photoradical addition reaction. This work has laid bases for the further development of novel industrial processes for the production of these drug molecules. The newly disclosed 1,3-diaza Cope rearrangement reaction is of particular interest and may inspire new synthetic applications.