Synthesis and intramolecular reactions of Tyr-Gly and Tyr-Gly-Gly related 6- O-glucopyranose esters

Abstract

6- O-( l-Tyrosylglycyl)- and 6- O-( l-tyrosylglycylglycyl)- d-glucopyranose were synthesized by condensation of the pentachlorophenyl esters of the respective di- and tripeptide with fully unprotected d-glucose. The intramolecular reactivity of the sugar conjugates was studied in pyridine–acetic acid and in dry methanol, at various temperatures and for various incubation times. The composition of the incubation mixtures was monitored by a reversed-phase HPLC method that permits simultaneous analysis of the disappearance of the starting material and the appearance of rearrangement and degradation products. To determine the influence of esterification of the peptide carboxy group on its amino group reactivity, parallel experiments were done in which free peptides were, under identical reaction conditions, incubated with d-glucose (molar ratios 1:1 and 1:5). Depending on the starting compound, different types of Amadori products (cyclic and bicyclic form), methyl ester of peptides, and Tyr-Gly-diketopiperazine were obtained.