Chemoenzymatic synthesis of a 3(IV), 6(III)-disulfated lewis(x) pentasaccharide, a candidate ligand for human L-selectin

Article abstract of DOI:10.1016/S0008-6215(97)10043-X

The disulfated pentasaccharide 3-O-SO₃/^--β-D-Galp-(1 → 4)-[α-L- Fucp-(1 → 3)]-6-O-SO₃/^-β-D-GlcpNAc-(1 → 3)-β-D-Galp-(1 → 4)-D-Glcp was prepared according to a chemoenzymatic approach, starting from 4- methoxybenzyl O-(4-O-acetyl-2,6-di-O-benzyl-β-D-galactopyranosyl)-(1 → 4)- O-2,3,6-tri-O-benzyl-β-D-glucopyranoside, obtained in six steps from hepta- O-acetyl lactosyl bromide. Coupling of this lactose derivative with O- (3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl) trichloracetimidate afforded, after dephthaloylation and re-N-acetylation, 4- methoxybenzyl O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1 → 3)-O-(2,6- di-O-benzyl-β-D-galactopyranosyl)-(1 → 4)-O-2,3,6-tri-O-benzylβ-D- glucopyranoside. Regioselective sulfation at the primary position of the glucosamine residue was then successfully achieved and the benzyl groups were removed. Enzymatic galactosylation of 4-methoxybenzyl O-(2-acetamido-2- deoxy-6-O-sulfo-β-D-glucopyranosyl)-(1 → 3)-O-β-D-galactopyranosyl-(1 → 4)-O-β-D-glucopyranoside sodium salt, and subsequent regioselective sulfation at position 3 of the outer galactose residue through the stannylene procedure, led then to 4-methoxybenzyl O-(3-sulfo-β-D-galactopyranosyl)-(1 → 4)-O-(2-acetamido-2-deoxy-6-sulfo-β-D-glucopyranosyl)-(1 → 3)-O-β-D- galactopyranosyl-(1 → 4)-O-β-D-glucopyranoside disodium salt, which was finally fucosylated using human milk α-(1 → 3/4)-fucosyltransferase affording, after anomeric deprotection, the target pentasaccharide.