Artificial carbohydrate antigens: synthesis of rhamnose disaccharides common to ShigellaflexneriO-antigen determinants

Abstract

Three disaccharides containing α-linked rhamnopyranoside units have been synthesised in a form suitable for covalent linkage to protein. The artificial antigens obtained in this manner represent structural elements similar to portions of the repeating unit of the ShigellaflexneriO-antigen. The glycosylation reactions leading to the disaccharides utilised silver trifluoromethanesulphonate and N,N-tetramethylurea, or sym-collidine, conditions which generated the three 1,2-trans-linked glycosides in high yield and stereospecificity. The blocking groups used in these syntheses are consistent with further chain extension to tri- and tetrasaccharides.2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl chloride and the 1,2-oxazoline derivative obtained from it were not effective in glycosylating the C-2 position of partially blocked rhamnopyranoside but 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-D-glucosyl bromide gave the desired 1,2-trans-2-amino-2-deoxyglucoside in good yield. Selective conversion of the phthalimido group to an acetamido function in the presence of an ester function was achieved, thereby extending the utility of the phthalimido protecting group to sequential oligosaccharide synthesis, in which 2-acetamido-2-deoxy-β-D-glucosides are internal units. Proton nmr evidence in support of the exo-anomeric effect is presented.