Synthesis of a New Proteasome Inhibitor Displaying an α-Keto β-Epoxyester Warhead

Abstract

In this work, the design and synthesis of a new proteasome inhibitor warhead has been accomplished. Chemical structure of the inhibitor displays three fragments: an α-keto β- epoxyester moiety as a warhead, a dipeptidyl linker and an azido-L-phenylalanine as a “clickable” part with a tag. The desired inhibitor has been prepared through a convergent synthesis of the three fragments. The synthesis of the warhead has two key steps: a Morita-Baylis-Hillman reaction and an epoxidation reaction.