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

Erythro N-protected alpha-amino epoxides, derived from alpha-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 N-omega-nitro-arginine exhibited selective inactivation of the cysteine proteases papain and cathepsin B, while they failed to inactivate the serine protease trypsin. (C) 1997 Elsevier Science Ltd.