The first synthesis of secondary sugar sulfonic acids by nucleophilic displacement reactions

The 4-deoxy-4-C-sulfonic acid and 6-deoxy-6-C-sulfonic acid derivatives of methyl α-d-gluco- and α-d-galactopyranosides were prepared by triflate-mediated nucleophilic displacement reactions, either with NaHSO3 or with AcSK. The triflate esters of methyl 2,3,4-tri-O-benzyl- 1, methyl 2,3,6-tri-O-benzyl-α-d-glucopyranoside 9 and methyl 2,3,6-tri-O-benzyl-α-d-galactopyranoside 5 provided methyl 6-deoxy-6-C-sulfo-α-d-glucopyranoside 4, methyl 4-deoxy-4-C-sulfo-α-d-galactopyranoside 12 and α-d-glucopyranoside 8, respectively. The triflate derivative of methyl 2,3,4-tri-O-benzyl-α-d-galactopyranoside 13 gave methyl 3,6-anhydro-2,4-di-O-benzyl-α-d-galactopyranoside 14. Formation of the 3,6-anhydro derivative was prevented by using 3,4-O-isopropylidene acetal protection to obtain methyl 6-deoxy-6-C-sulfo-α-d-galactopyranoside 19. The aim of the research is to replace the sulfate esters by sulfonic acids in the repeating oligosaccharide units of glycosaminoglycans or in different oligosaccharide ligands.