Acetylated glucopyranosyl esters of enkephalins

Acetylated d -glucopyranosyl esters of enkephalins were prepared by two different fragment condensation procedures involving direct participation of imidazole in the ester linkage formation. By both methods anomeric mixtures of d -glucosyl esters were obtained and resolved by column chromatography. Depending on coupling conditions, racemization of either the C-terminal or the penultimate amino acid residue of the enkephalin molecule occurred. The glucoconjugates with inverted stereochemistry were quantitated and separated from the main product by reversed-phase high-performance liquid chromatography. The opioid agonist potencies of the synthesized glucopyranosyl esters of enkephalins on electrically stimulated guinea pig ileum and mouse vas deferens preparations were determined in comparison with Leu⁵]enkephalin.