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

Epoxomicin (1), a peptide alpha',beta'-epoxyketone isolated from the actino mycete strain No.Q996-17, possesses potent in vivo anti-tumor and anti-infl ammatory activities. In this paper, we report the first syntheses of epoxom icin, [H-3]-epoxomicin, and a biotinylated epoxomicin analog as well as the absolute configuration of the epoxide stereocenter. The natural product an d derivatives have permitted the first identification of the proteasome as the specific cellular target of epoxomicin. (C) 1999 Elsevier Science Ltd. All rights reserved.