Synthesis of met- and leu-enkephalin analogues containing chiral N,N′-ethylene-bridged phenylalanyl-methionine and -leucine

Abstract

Conformationally constrained N,N′-ethylene-bridged dipeptides (eXX′) were conveniently synthesized in two steps using (R)- or (S)-phenylalanine (X = F) and -methionine (X′= M)[-leucine (X′= L)] as starting materials.

These dipeptides are diastereoisomeric or enantiomeric, and were used as the carboxyl terminal residues of enkephalin analogues [H–tyrosyl–D-alanyl–glycyI–eXX′–OEt]. The opiate activities of these pentapeptides were examined preliminarily by the mouse vas deferens assay, suggesting that these enkephalin analogues possess receptor- binding affinities.