CHEMOENZYMATIC SYNTHESIS OF A 3(IV),6(III)-DISULFATED LEWIS(X) PENTASACCHARIDE, A CANDIDATE LIGAND FOR HUMAN L-SELECTIN

The disulfated pentasaccharide eta-D-Galp-(1-->4)-[alpha-L-Fucp-(1-->3 )]-6-O-SO3- beta-D-GlcpNAc-(1-->3)-beta-D-Galp-(1-->4)-D-Glcp was prep ared according to a chemoenzymatic approach, starting from 4-methoxybe nzyl -2,6-di-O-benzyl-beta-D-galactopyranosyl)-(1-->4)- O-2,3,6-tri-O- benzyl-beta-D-glucopyranoside obtained in six steps from hepta-O-acety l lactosyl bromide. Coupling of this lactose derivative with -(3,4,6-t ri-O-acetyl-2-deoxy-2-phthalimido-beta-D- glucopyranosyl) trichloracet imidate afforded, after dephthaloylation and re-N-acetylation, 4-metho xybenzyl 2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1-->4) -->4)-O-2, 3,6-tri-O-benzyl-beta-D-glucopyranoside. Regioselective sulfation at t he primary position of the glucosamine residue was then successfully a chieved and the benzyl groups were removed. Enzymatic galactosylation of 4-methoxybenzyl o-2-deoxy-6-O-sulfo-beta-D-glucopyranosyl)-(1-->3) -galactopyranosyl-(1-->4)-O-beta-D-glucopyranoside sodium salt, and su bsequent regioselective sulfation at position 3 of the outer galactose residue through the stannylene procedure, led then to 4-methoxybenzyl O-(3-sulfo-beta-D-galactopyranosyl)-(1-->4) ranosyl)-(1-->3)-O-beta-D -galactopyranosyl-(1-->4) -O-beta-D-glucopyranoside disodium salt, whi ch was finally fucosylated using human milk alpha-(1-->3/4)-fucosyltra nsferase affording, after anomeric deprotection, the target pentasacch aride. (C) 1998 Elsevier Science Ltd.