Synthesis and properties of N-glycosylimidazoles

Abstract

In a model study concerned with the mechanism of glycosidase action, six N-glycosylimidazoles and five N-(tetra- O-acetyl-glycosyl) imidazoles have been synthesized by the condensation of the appropriate tetra-O-acetyl-glycosyl halide with imidazole.

These compounds have been characterised by their elemental analysis, optical rotation and NMR spectra. In all cases the beta-anomeric compounds predominated over those with alpha-configuration in the reaction products.

Analysis of 1H NMR data was carried out on a first order basis,and also by non-iterative and iterative calculation procedures in order to establish the conformations of the N-glycosylimidazoles. The analysis revealed that under certain conditions, in four compounds the sugar pyranose ring is distorted from the normal 4C₁ conformation. This distortion has been interpreted in terms of the operation of the reverse anomeric effect.

The hydrolytic stabilities of 1-alpha- and beta-D-glucopyranosylimidazoles have been examined in water, pH 3.0 sodium formate buffer, O.56M formic acid, 6N-hydrochloric acid, 10N-sulphuric acid and 1N NaOH. Optical rotation measurements, paper chromatography and analysis for estimation of glucose failed to detect any evidence of hydrolysis. This result is strong evidence against the nucleophilic intervention of a histidinyl side chain in glycosidase action. Hydrolytic cleavage was also attempted with solutions of (yeast) alpha- and (almond) beta-glycosidases, and no glucose was released under conditions in which standard compounds methyl alpha- D-glucoside and cellobiose were hydrolysed significantly.

The ORD/CD curves of N-glycosylimidazoles and a series of p-nitrophenyl-glycosides have been examined as an aid to establishing anomeric configurations for N-glycosylimidazoles. In general anomeric pairs of compounds show ORD/CD curves of opposite sign, but some exceptions have been observed in the case of N-glycosylimidazoles.

1-alpha- and beta-D-glucopyranosylimidazoles were found to possess inhibitory properties towards the enzymes (yeast) alpha-glucosidase, (almond) beta-glucosidase and lysozyme. These properties have been investigated in detail. The alpha-anomer shows an unexpectedly high degree of inhibitory behaviour.