Synthesis and C-13 NMR investigation of novel Amadori compounds (1-amino-1-deoxy-D-fructose derivatives) related to the opioid peptide, leucine-enkephalin

The N-(1-deoxy-D-fructos-1-yl) derivatives (Amadori compounds) of the endogenous opioid pentapeptide, leucine-enkephalin (11), leucine-enkephalin methyl ester (12) and of structurally related peptides (9, 10) are synthesized. The equilibrium compositions of the prepared Amadori compounds 9-12 in D2O and [H-2(6)]DMSO are determined using C-13 NMR spectroscopy. In water, the beta-pyranose, a-furanose and beta-furanose forms are detected, the beta-pyranose tautomer being the most abundant at equilibrium (67-75%). The alpha-pyranose form and open-chain keto form are not detected. In dimethyl sulfoxide, the equilibrium compositions of 9-12 are markedly shifted towards a higher proportion of furanose forms, amounting to two-thirds of the mixture. In addition to the alpha- and beta-furanoses and beta-pyranose tautomers, DMSO solutions of compounds 9-12 contain at equilibrium a relatively high proportion of the acyclic hydrate (gem-diol) form (ca. 10%).