Total Synthesis of Salinosporamide A

2005-06-15T00:00:00Z (GMT) by Atsushi Endo Samuel J. Danishefsky
Total synthesis of potent proteasome inhibitor salinosporamide A (<b>1</b>) has been accomplished, which features strictly substrate-controlled operations starting with the only chiral center of (<i>R</i>)-pyroglutamic acid. The consecutive quaternary carbons within <b>1</b> have been efficiently constructed by manipulation of two intramolecular reactions:  (1) carbonate-mediated internal acylation of imidate ester (<b>4 </b>→ <b>14</b>) and (2) selenocyclization of aldehyde to exocyclic methylene group (<b>5 </b>→ <b>18</b>).