November 5, 1999

The Synthesis of Bicyclic Lactam Based His-Pro Building Blocks: the Effect of Substituent Polarity on an Intramolecular Bond Migration

Wenhua Chu and Kevin D. Moeller

Tetrahedron Lett., 1999, 40(45), 7939-7943

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.