Synthesis and structural studies of branched 2-linked trisaccharides related to blood group determinants

A series of trisaccharide glycosides, Fuc-(1 → 2)-β-Gal-(1 → 3)-β-X-OMe (X = GlcNAc, Glc, 2-deoxy-Glc) related to the blood group determinant Led have been synthesised both as their α- and β-Fuc anomers together with the component disaccharide starting compounds. The conformational properties of the six trisaccharides together with their parent disaccharides have been investigated by NMR spectroscopy (proton and carbon chemical shifts and proton NOEs) in combination with computer modeling using the Monte Carlo approach and the HSEA force field using the GEGOP programme. The interaction between the terminal fucose unit and the reducing unit was probed by substitution of the bulky NAc group with hydroxyl and deoxy substituents, respectively. Compounds with severe steric interactions were identified by the non-additivity of their carbon chemical shifts. This was subsequently confirmed by the detailed conformational assessment by NOE spectroscopy and computer modeling. The most severe contacts arose in the α-l-Fuc derivatives, whereas the β-linked l-Fuc derivatives only in one case exhibit severe steric interaction as probed by the NMR parameters.