The synthesis of bicyclic lactam based His-Pro building blocks: the effect of substituent polarity on an intramolecular bond migration

A strategy for constructing bicyclic lactam amino acid building blocks with imidazole sidechains is reported. The synthetic route described utilizes an electrochemical amide oxidation to functionalize a proline derivative, and then a sequential cyclization-rearrangement strategy to construct a substituted six-membered ring lactam. Alternatively, the seven-membered ring lactams were obtained without rearrangement when electron withdrawing groups were present beta to the amide carbonyl. (C) 1999 Elsevier Science Ltd. All rights reserved.