Intramolecular rearrangement of the monosaccharide esters of an opioid pentapeptide: formation and identification of novel Amadori compounds related to fructose and tagatose

Abstract

Intramolecular rearrangements leading to Amadori adducts 4 and 5 from monosaccharide esters 1–3 in which either D-glucose, D-mannose or D-galactose is linked through its C-6 hydroxy group to the C-terminal carboxy group of the endogenous opioid pentapeptide leucine-enkephalin (H-Tyr-Gly-Gly-Phe-Leu-OH) are reported. The formation of bicyclic compounds 4 and 5 from the corresponding monosaccharide esters is much faster than formation of the Amadori product from the parent free sugar and leucine-enkephalin. Bicyclic ketoses 4 and 5 are each transformed by hydrolysis into the corresponding 1-amino-1-deoxy-D-fructose (6) and -D-tagatose (7) Amadori products of leucine-enkephalin, indistinguishable by their physical and spectroscopic data from compounds 6 and 7 obtained by independent syntheses. The equilibrium compositions of the prepared Amadori compounds 4–7 in aqueous solutions have been determined by 13C NMR spectroscopy.