The blood group ABO antigens are residual oligosaccharides of glycosphingolipids and glycoproteins expressed on erythrocytes and endothelial cells. Antigens of blood groups A and B include common terminal trisaccharides – (GalNAcα-(1→3)-[Fucα-(1→2)]-Galβ) and (Galα-(1→3)-[Fucα-(1→2)]-Galβ) known as A and B trisaccharides. These fragments are connected to the further monosacchride residue by β-glycosidic linkage. The type of this linkage and of monosaccharide residue allows to divide A and B tetrasaccharides into subtypes: β-(1→3)- or β-(1→4)-connection with GlcNAcβ provides types 1 and 2, β-(1→3)-connection with GalNAcα or GalNAcβ provides types 3 and 4 respectively.
The presence of the common terminal trisaccharide fragment in A and B tetrasaccharides gives an opportunity to use block synthetic approach as the most effective pathway to these compounds. We have developed a new strategy for the synthesis of A and B blood group tetrasaccharides (types 1–4), based on [3+1]-glycosylation of sutably protected glucosamine or galactosamine glycosyl acceptor by A or B trisaccharide glycosyl donor.
Peracetylated trichloroacetimidates 1 and 2 corresponding to A and B trisaccharides were chosen as glycosyl donors for [3+1] block scheme. Glycosylation reactions by 1 and 2 were carried out in CH3CN with the use of TMSOTf as catalyst. Condensation of comounds 1 and 2 with glycosyl acceptors 3, 4, 5, and 6 led to the types 1, 2, 3, and 4 of A and B antigens respectively. Required β-anomers were the major products in all cases. Regioselective glycosylation of 3-OH-group in N-acetyl-glucosamine derivative 7 by glycosyl donors 1 and 2 and further fucosylation of free 4-OH-group by benzylated imidate 8 (TMSOTf/Et2O) provided pentasaccharides A Lewis B and B Lewis B. All obtained oligosaccharides were deprotected by usual methods. Synthetic glycolipid constructs 9 were then obtained and used for ABO quality control of the commercial blood group monoclonal antibodies.
