Total synthesis of the potent proteasome inhibitor epoxomicin: A useful tool for understanding proteasome biology

Abstract

Epoxomicin (1), a peptide α',β'-epoxyketone isolated from the actinomycete strain No. Q996-17, possesses potent in vivo anti-tumor and anti-inflammatory activities. In this paper, we report the first syntheses of epoxomicin, [3H]-epoxomicin, and a biotinylated epoxomicin analog as well as the absolute configuration of the epoxide stereocenter. The natural product and derivatives have permitted the first identification of the proteasome as the specific cellular target of epoxomicin.