Stereocontrolled Synthesis and Conformational Analysis of a Series of Disaccharides α,ß-d-GlcA-(1→3)-α-L-Fuc.

D-Glucuronic acid is a fundamental building block of many biologically important polysaccharides, either in its non-substituted form or bearing a variety of substituents, among them sulfates. We have previously performed a study of the effects of exhaustive sulfation on the conformational behavior of ß-gluronopyranosides. Herein, we report an investigation comparing α- and ß-derivatives of this monosaccharide within the title disaccharides using NMR and quantum chemistry approaches. It was found that for α-linked disaccharides, the introduction of sulfates did not greatly affect their conformational behavior. However, for ß-derivatives, considerable conformational changes were observed. In general, they resemble those that took place for the monosaccharides, except that NOESY experiments and calculations of intra-ring spin-spin coupling constants suggest the presence of a 1S5 conformer along with 3S1 in the fully sulfated disaccharide. During the synthesis of model compounds, hydrogen bond-mediated aglycone delivery was used as an α-directing stereocontrol approach in the glucuronidation reaction.

Сonformational study of persulfated propyl glucuronide.

Glucuronic acid is an important constituting block of biologically active glycosaminoglycans where it can be present in non-sulfated, mono-sulfated and di-sulfated forms. Despite that some investigators reported previously that the exhaustively sulfated glucuronic acid moiety was characterized with unusual 1H-1H coupling constants and some times chemical shifts, these were just qualitative studies in which their authors suggested that the mentioned deviations in NMR spectra might mean complete inversion of the normal D-pyranoside chair conformation 4C1 to 1C4. Herein we outline a detailed conformational investigation showing that the distortion in the pyranoside ring of the persulfated glucuronic acid cannot be described simply with 4C1↔1C4 inversion. Instead, the experimental NOE data clearly indicate that two skew-boat conformers, OS2 and 3S1, provide significant contribution to the conformational equilibrium.