Chemoenzymatic synthesis of NeuAc alpha-(2 -> 3)-Gal beta-(l -> 3)-[NeuAc alpha-(2 -> 6)]-GalNAc alpha 1-O-(Z)-Serine (N-protected MUC II oligosaccharide-serine)

An efficient synthesis of NeuAcalpha-(2-->3)-Galbeta-(1-->3)-[NeuAcalpha-(2-->6)]GalNAcalpha1-O-(Z)-Serine (N-protected MUC 11 oligosaccharide-serine, 14) by a chemoenzymatic strategy is described. The enzymatic reaction of GalNAcalpha1-O-(Z)-Ser-OAll 7 with pNP-beta-Gal in the presence of recombinant beta1,3-galactosidase from Bacillus circulans gave Galbeta-(1-->3)-GalNAcalpha1-O-(Z)-Ser-OAll 3 in 68%. The introduction of two sialic acids into 3 was accomplished by a stepwise method. The branched Galbeta-(1-->3)-[NeuAcalpha(2-->6)]-GalNAcalpha1-O-(Z)-Ser-OAll 11 was constructed by a chemical method. Sialylation at the C-3 position of the terminal Gal residue on Galbeta-(1-->3)-[NeuAcalpha-(2-->6)]-GalNAcalpha1-O-(Z)-Serine 2 using alpha2,3-(O)-sialyttransferase from rat liver gave a target compound 14 in a practical yield.