Synthesis of 1‐(m‐Hydroxybenzyl)‐Substituted 1,2,3,4‐Tetrahydroisoquinoline‐3‐carboxylic Acid Derivatives as Opioid Peptide Mimetics − Unexpected Amide Bond Cleavages under Mild Conditions

Abstract N‐Glycyl‐(1R,3S)‐1‐(m‐hydroxybenzyl)‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid (Tic) was prepared as a Tyr‐Tic dipeptide mimetic for exploration of its potential as a delta opioid receptor selective ligand. The compound was successfully obtained by a stereoselective synthesis starting from L‐Tic. In the course of the reactions, unusual peptide bond cleavages were observed under mild conditions, and reaction mechanisms have been proposed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)