A practical synthesis of chiral tricyclic cyclopenta[b]benzofuran, a key intermediate of Beraprost

Abstract

A novel formal synthesis of Beraprost (1) is described. The tricyclic cyclopent[b]benzofuran core is efficiently prepared from (−)-Corey lactone diol in 12 steps with an overall yield of 37.4%. Key features of the strategy include a ring-closing metathesis reaction and aromatization to form the tricyclic cyclopenta[b]benzofuran framework, and selective halogenation/formylation to install the butyrate side-chain.