Conformational study of synthetic Δ4-uronate monosaccharides and glycosaminoglycan-derived disaccharides

Sixteen Delta(4)-uronate monosaccharides were chemically synthesized. Their carboxy group was protected as a methyl or benzyl ester, the anomeric hydroxyl group as a benzyl glycoside and the 2 and 3 hydroxyl groups were protected with different substitution patterns as both ester and ether derivatives. Disaccharides containing Delta(4)-uronates were prepared from heparin using heparin lyases. Their carboxy group was unprotected or protected as a benzyl ester and the two hydroxyls in the uronate moiety were free, as O-sulfo derivatives or acylated. The conformation of these unsaturated uronate monosaccharide and disaccharide residues was studied using H-1 NMR by examining interproton vicinal coupling constants. The Delta(4)-uronate residue adopted either the H-2(1) or the H-1(2) conformations. The equilibrium between these two conformers was shown to be controlled by substitution pattern. (C) 1998 Elsevier Science Ltd. All rights reserved.