Synthesis and characterization of mannose-related imidazolidinones formed by the intramolecular rearrangement of the mannopyranose ester of leucine-enkephalin

The early glycation products of the Maillard reaction: mass spectrometric characterization of novel imidazolidinones derived from an opioid pentapeptide and glucose

“…We found for the first time that, depending on the reaction conditions, in addition to Amadori rearrangement, an alternative pathway for the carbohydrate‐induced modification of peptides is possible, yielding hexose‐related imidazolidinones 13,. 14 These results point to the possibility that, depending on the physiological environment, similar carbohydrate‐related imidazolidinones may also be generated as products of the early stage of the Maillard reaction in vivo .…”

“…To investigate the early glycation products, in our recent studies we used carbohydrate‐peptide esters in which the sugar moiety ( 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) as model compounds for the study of the Maillard reaction in vitro 12–14. We found for the first time that, depending on the reaction conditions, in addition to Amadori rearrangement, an alternative pathway for the carbohydrate‐induced modification of peptides is possible, yielding hexose‐related imidazolidinones 13,.…”

Stereochemical Assignment of Diastereomeric Imidazolidinone‐Ring‐Containing Bicyclic Sugar‐Peptide Adducts: NMR Spectroscopy and Molecular Calculations

“…[26,27] Two isomers may be formed in the intramolecular reactions. However, the transformation of 3 into the corresponding imidazolidinone compound took place with complete stereoselectivity, resulting in the formation of (2R)-6 in which the pentitolyl residue and hydroxybenzyl group have a trans arrangement and C2 of the imidazolidinone ring has the R configuration.…”

“…Compounds 4Ϫ6 are obtained from the corresponding monosaccharide esters of Leu-enkephalin (1Ϫ3) in which either -glucose, -galactose or -mannose is linked through its C-6 hydroxy group to the C-terminal carboxy group of the parent pentapeptide [25] by a spontaneous intramolecular cyclization reaction ( Figure 1). [26,27] Two isomers may be formed in the intramolecular reactions. However, the transformation of 3 into the corresponding imidazolidinone compound took place with complete stereoselectivity, resulting in the formation of (2R)-6 in which the pentitolyl residue and hydroxybenzyl group have a trans arrangement and C2 of the imidazolidinone ring has the R configuration.…”

“…However, the transformation of 3 into the corresponding imidazolidinone compound took place with complete stereoselectivity, resulting in the formation of (2R)-6 in which the pentitolyl residue and hydroxybenzyl group have a trans arrangement and C2 of the imidazolidinone ring has the R configuration. [27] Consequently, the protons at C2 and C4 have a trans relative geometry. The conversion of either 1 or 2 to the corresponding imidazolidinones exhibited a low degree of stereocontrol and resulted in different amounts of trans and cis isomers.…”