Total Synthesis of Salinosporamide A

Abstract
Total synthesis of potent proteasome inhibitor salinosporamide A (1) has been accomplished, which features strictly substrate-controlled operations starting with the only chiral center of (R)-pyroglutamic acid. The consecutive quaternary carbons within 1 have been efficiently constructed by manipulation of two intramolecular reactions: (1) carbonate-mediated internal acylation of imidate ester (4 → 14) and (2) selenocyclization of aldehyde to exocyclic methylene group (5 → 18).