A convenient and versatile synthesis of 6, 5- and 7, 5-fused bicyclic lactams as peptidomimetics

Abstract

Chemo-selective reduction of the pyroglutamate ring carbonyl in a serine-pyroglutamate or homoserine to pyroglutamate dipeptide gave a hemiaminal. Treatment of the hemiaminal with a catalytic amount of TFA in CH2Cl2 generated an N-acyliminium ion that was intramolecularly trapped by the side-chain hydroxyl to give a 6, 5 or 7, 5-bicyclic lactam. © 2001 DuPont Pharmaceuticals Company.