Chemical synthesis of β-D-GlcpA(2SO4)-(1→3)-D-GalpNAc(6SO4), the disaccharide repeating unit of shark cartilage chondroitin sulfate D, and of its methyl β-D-glycoside derivative

Abstract

The syntheses of sodium O-(disodium 2-O-sulfonato-β-D-glucopyranosyluronate)-(1→3)-2-acetamido-2-deoxy-6-O-sulfonato-D-galactopyranose 1, which represents a structural element of shark cartilage chondroitin sulfate D, and of its methyl β-D-glycoside derivative 2 are reported for the first time. The glucuronyl donor 10 is prepared in a straightforward manner from D-glucose, whereas the glycosyl acceptors 20 and 21 are obtained from known 3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamido-1-O-trichloroacetimidoyl-α-D-glucopyranose through glycosylation with benzyl alcohol and methanol, respectively, and subsequent transformation into D-galacto synthons by selective inversion of configuration at C-4. Unexpected pyranose → furanose ring contraction as well as 3,6-anhydro-derivative formation in the D-galacto series are also reported. Stereocontrolled coupling of the imidate 10 with the alcohols 20 and 21 afforded the corresponding β-linked disaccharide derivatives 24 and 25, respectively, which are submitted to radical reduction of the N-trichloroacetyl groups, O-desilylation, saponification, O-sulfonation, and catalytic hydrogenation to provide the target molecules 1 and 2, respectively, in high yields.