Functionalized erythro N-protected α-amino epoxides. Stereocontrolled synthesis and biological activity

Erythro N-protected α-amino epoxides, derived from α-amino acids bearing functionalized side chains, were synthesized. The key synthetic step is a stereoselective reduction of the corresponding haloketone either to the halohydrin or directly to the epoxide. The side chains include ester, ether and alcohol, nitro guanidine, carbamate and amine functional groups, derived from aspartate and glutamate, serine, arginine, and lysine, respectively. The epoxides derived from lysine and Nϖ-nitro-arginine exhibited selective inactivation of the cysteine proteases papain and cathepsin B, while they failed to inactivate the serine protease trypsin.