Synthesis of Lewis A trisaccharide analogues in which d-glucose and l-rhamnose replace d-galactose and l-fucose, respectively

In our effort to design a safe anti-cancer vaccine based on the tumor associated carbohydrate antigen LeaLex, we are studying the cross-reactivity between the Lea natural trisaccharide antigen and analogues in which the l-fucose, d-galactose, and/or d-glucosamine residues are replaced by l-rhamnose or d-glucose, respectively. We describe here the chemical synthesis of two such Lea trisaccharide analogues. In one trisaccharide, d-glucose replaces d-galactose and in the second analogue l-rhamnose and d-glucose replace l-fucose and d-galactose, respectively. Introduction of the rhamnose and fucose moiety onto the poorly reactive 4-OH group of the N-acetylglucosamine residue in a disaccharide acceptor was successful after bis-N-acetylation of the amine group. These analogues will be used in competitive binding experiments with anti-Lea antibodies and their solution conformations will be studied.