Solid phase synthesis of C-terminal carbohydrate modified enkephalins

1-Azido-2,3,4-tri-O-acetyl-β-D-glucuronic acid (1), immobilised on 2-chlorotrityl and NovaSyn TGR resin, was efficiently reduced to its corresponding resin bound glycosyl amine (3) using propane-1,3-dithiol and triethylamine. Subsequent acylation of (3) with (1), generated the carbohydrate dimer (4). In addition, Fmoc based peptide syntheses performed on (3) and (4) afforded the C-terminal modified Leu and Met-enkephalins (7–10). Preliminary pharmacological evaluation of these compounds identified glycopeptide (7) as a potent and selective δ-opioid receptor agonist.