Glycosylation of lactose: synthesis of branched oligosaccharides involved in the biosynthesis of glycolipids having blood-group I activity

Abstract

Methyl 4- O-(2- O-benzoyl-4,6- O-benzylidene-β- d-galactopyranos)-2,3,6-tri- O-benzoyl-β- d-glucopyranoside ( 2) was [re[ared in four steps from methyl β-lactoside. Crystalline 2 was a convenient substrate for the synthesis of branched oligosaccharides derived from lactose. High-yield glycosylations were performed first at the 3′-position and then, after removal of the benzylidene group, at the 6′-position, using trichloroacetimidates of N-phthaloylamino sugars. 3,4,6-Tri- O-acetyl-2-deoxy-2-phthalimido-β- d-glucopyranosyl trichloroacetimidate was thus used in two consecutive glycosylations, and also in a simultaneous disubstitution of the triol 9, leading in each sequence to the branched tetrasaccharide, β- d-Glc p-NAc-(1→3)-[β- d-Glc pNAc-(1→6)]-β- d-Gal p-(1→4-β- d-GlcOME. Similar glycosylations performed with 3,6-di- O-acetyl-2-deoxy-2-phthalimido-4- O-(2,3,4,6- tetra- O-acetyl-β- d-galactopyranosyl)-β- d-g;ucopyranosyl trichloroacetimidate afforded the branched hexasaccharide β- d-Gal p-(1→4)-β- d-Glc pNAc-(1→3)-[β- d-Gal p-(1→4)-β- d-Glc pNAc-(1→6)]- β- d-Glc pNAc-(1→6)-β- d-Gal p-(1→4)-β- d-GlcOMe, which corresponds to the human-milk oligasaccharide lacto- N- neohexaose and has a strong blood-group activity.