A concise, total synthesis of the TMC-95A/B proteasome inhibitors.

A concise, total synthesis of the proteasome inhibitors TMC-95A/B has been accomplished. The synthesis features the use of an L-serine-derived E-selective modified Julia olefination reaction to ultimately control the stereochemical outcome of the highly oxidized tryptophan fragment. Additionally, the limited use of protecting groups at a late stage of the total synthesis allowed for its completion in an efficient manner.