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

Abstract

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 [²H₆]DMSO are determined using ¹³C NMR spectroscopy. In water, the β-pyranose, α-furanose and β-furanose forms are detected, the β-pyranose tautomer being the most abundant at equilibrium (67–75%). The α-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 α- and β-furanoses and β-pyranose tautomers, DMSO solutions of compounds 9–12 contain at equilibrium a relatively high proportion of the acyclic hydrate (gem-diol) form (ca. 10%).