Bioinspired enantioselective total syntheses of antibacterial callistrilones enabled by double SN2′ cascade

Abstract

A bioinspired, catalytic approach to the enantioselective total syntheses of antibacterial callistrilones A, C-E and 13-epi-callistrilone E natural products containing an unprecedented, sterically compact [1]benzofuro-[2,3-a]xanthene 6/6/6/5/6/3-fused hexacyclic skeleton is described. The key features of the synthesis include a highly regio- and diastereoselective double S_N2′ cascade reaction, Lewis acid catalysed Michael addition and late stage diastereoselective epoxide formation from the sterically hindered β-face of the alkene as the key steps.