Synthesis of oligosaccharides related to the HNK-1 antigen .1. Synthesis of selectively protected allyl 3-O-[methyl(beta-D-glucopyranosyl)uronate]-beta-D-galactopyranoside

The glycosylation of several mono-and dihydroxyl glycosyl accepters based on allyl beta-D-galactopyranoside with completely acylated glucuronyl bromides under the Helferich reaction conditions was studied in order to develop a method for the preparative synthesis of selectively protected disaccharide beta-D-GlcA-(1 --> 3)-beta-D-Gal in a form that can be used for further preparation of corresponding glycosyl donors and spacerated derivatives. We found that 1,2-orthoesters were the major primary products of the reaction, and their further conversion into isomeric glycosides depended on pH and can be regulated by the type of molecular sieves used. When Acid Washed Molecular Sieves AW 300 were used, glycosides were predominantly synthesized. No selective formation of the (1 --> 3)-bound disaccharide was observed upon glycosylation of glycosyl accepters with 2,3- and 3,4-diol groupings. This (1 --> 3)-bound disaccharide was most efficiently synthesized by glycosylation of allyl 4,6-O-benzylidene-2-O-benzoyl-beta-D-galactopyranoside with pivaloylated glucuronyl bromide. With acetylated or benzoylated glucuronyl bromides or with pivaloyl glucuronyl imidate, this galactoside can also be glycosylated but with a lower yield of the target (1 --> 3)-bound disaccharide and lower glycosylation regioselectivity.