Synthesis of a tetrasaccharide of the genus-specific lipopolysaccharide epitope of Chlamydia

Abstract

Allyl 2-acetamido-2-deoxy-3,4- O-(1,1,3,3,-tetraisopropyldisiloxan-1,3-diyl)-β- d-glucopyranoside was coupled with methyl (4,5,7,8-tetra- O-acetyl-3-deoxy-α- d- manno-2-octulopyranosyl bromide)onate ( 1) to give a good yield of the α-(2→6)-linked disaccharide, isolated after deacetylation and regioselective conversion into the corresponding 7′,8′- O-carbonyl or 7′,8′- O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl) derivatives, respectively. Subsequent glycosylation with 1 gave a high yield of the α- and β-(2″→4′)-linked trisaccharide derivatives 16 and 18, whereas block synthesis using the α-(2→8)-linked Kdo-disaccharide bromide derivative 19 afforded a low yield of the corresponding α- and β-(2″→4′)-linked tetrasaccharide derivatives 20 and 22. Removal of the protecting groups furnished the disaccharide allyl O-(sodium 3-deoxy-α- d- manno-2-octulopyranosylonate)-(2→6)-2-acetamido-2-deoxy-β- d-glucopyranoside, the trisaccharide allyl O-(sodium 3-deoxy-α- d- manno-2-octulopyranosylonate)-(2→4)-(sodium 3-deoxy-α- d- manno-2-octulopyranosylonate)- (2→6)-2-acetamido-2-deoxy-β- d-glucopyranoside, and the tetrasaccharide allyl O-(sodium 3-deoxy-α- d- manno-2-octulopyranosylonate)-(2→8)-(sodium 3-deoxy-α- d- manno-2-octulopyranosylonate)- (2→4)-(sodium 3-deoxy-α- d- manno-2-octulopyranosylonate)-(2→6)-2-acetamido-2-deoxy-β- d-glucopyranoside in high yield. Copolymerization of the allyl glycosides with acrylamide gave artificial polyvalent haptens suitable for defining epitope specificities of monoclonal antibodies directed against Chlamydia lipopolysaccharides.