Examination of the influence of C5-hydroxymethyl group and configurations of hydroxyl groups at C2, C3, and C4 stereocentres on the N-glycosidic torsion: synthesis and X-ray crystallographic investigation of N-(d-ribopyranosyl)alkanamides as N-glycoprotein linkage region analogs

Abstract

N-Linked glycosylation is not only present in eukaryotes but also occurs in archaea and bacteria and is mainly characterized by the β-glucosylamine linkage to the asparagine (GlcNAcβAsn). Earlier crystallographic studies aimed at understanding the structural significance of the linkage region constituents revealed that N-glycosidic torsion, ϕN is influenced considerably by variation in the glycan part as compared to the aglycon moiety. The ϕN value observed for XylβNHAc deviated maximum as compared to that of the model compound, GlcNAcβNHAc. The present work was undertaken to assess the influence of ribose on the N-glycosidic torsions and molecular assembly. Several ribopyranosyl alkanamides have been synthesized and crystal structures of three of them have been solved. A comprehensive crystal structure analysis of ribosyl alkanamides along with xylosyl and arabinosyl alkanamides showed the wide range of deviations in their ϕN values as compared to the negligible deviation shown by hexopyranosyl alkanamides. This study revealed the importance of C5-hydroxymethyl group and hydroxyl group configurations at C2, C3, and C4 stereocentres in controlling the N-glycosidic torsions.