Enantioselective Total Synthesis of (−)-Salinosporamide A (NPI-0052)

Abstract

A novel enantioselective total synthesis of 20S proteasome inhibitor Salinosporamide A (NPI-0052; 1) is presented. Key features include intramolecular aldol cyclization of 6 to simultaneously generate the three chiral centers of advanced intermediate 5, cyclohexene ring addition using B-2-cyclohexen-1-yl-9-BBN, and inversion of the C-5 stereocenter by oxidation followed by enantioselective enzymatic reduction.