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

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.