Synthesis of hexose-related imidazolidinones: Novel glycation products in the Maillard reaction

Carbohydrate-peptide esters which mimic the reactivity of sugar 6-phosphate s in nonenzymatic glycations were used as model compounds for the study of the Maillard reaction in vitro. We found that intramolecular cyclization of the monosaccharide ester in which the sugar moiety (D-glucose or D-galacto se) is linked, through the C-6 hydroxy group, to the C-terminal carboxy gro up of the endogenous opioid pentapeptide leucine-enkephalin, in methanol as the solvent, resulted in the formation of imidazolidinone diastereoisomers having cis or trans relative geometry of the substituents at the imidazoli dinone ring moiety. The diastereoisomeric imidazolidinones were separated a nd each transformed by hydrolysis into the corresponding D-gluco- and D-gal acto-related imidazolidinone products of leucine-enkephalin. Along with the previous evidence that, from the same sugar-peptide esters by changing the reaction conditions Amadori rearrangement products could be obtained [Horv at et al. (1998) J Chem Soc Perkin Trans 1:909-13], the presented results p oint to the possibility that similar carbohydrate-related imidazolidinones may also be generated in the early stage of the Maillard reaction in vivo.