Stereoselective synthesis of β-d-GlcNAc-(1 → 4)-d-Glc disaccharide starting from lactose

• The synthesis of beta-d-GlcNAc-(1 → 4)-d-Glc disaccharide starting from lactose is described.
• The approach involves the transformation of the beta-d-galactopyranosyl unit into a N-acetyl-beta-d-glucosaminyl one.
• The conversion of the β-d-talopyranosyl disaccharide into the β-d-mannopyranosyl one is achieved by stereoselective hydroboration–oxidation.
• The β-d-mannopyranosyl unit is transformed into the beta-d-N-acetyl-glucosaminyl one by amination with inversion of configuration by SN2 displacement.

The stereoselective preparation of the β-d-GlcNAc-(1 → 4)-d-Glc disaccharide starting from known 4-O-[6-O-(1-methoxy-1-methylethyl)-3,4-O-isopropylidene-β-d-talopyranosyl]-2,3:5,6-di-O-isopropylidene-aldehydo-d-glucose dimethyl acetal (2), in turn easily obtained from lactose, is reported. Key steps of this new procedure, that avoids the glycosylation reaction, are (a) a first epimerization at C-4′ through an unusual procedure involving a completely stereospecific hydroboration–oxidation of the enol ether group of the hex-4-enopyranoside 4, obtained from 3 by base promoted acetone elimination, (b) an amination with inversion by SN2 reaction on an imidazylate intermediate, and, finally, (c) N-acetylation followed by complete deprotection.

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