Synthesis of clasto-lactacystin beta-lactone and analogs thereof

摘要

The present invention is directed to an improved synthesis of clasto-lactacystin-beta-lactone, and analogs thereof, that proceeds in fewer steps and in much greater overall yield than syntheses described in the prior art. The synthetic pathway relies upon a novel stereospecific synthesis of an oxazoline intermediate and a unique stereoselective addition of a formyl amide to the oxazoline. Also described are novel clasto-lactacystin-beta-lactones, and analogs thereof and their use as proteosome inhibitors.