Synthesis of Haemophilus influenzae carbohydrate surface antigens

Abstract

The pathogenic bacteria Haemophilus influenzae, causing, i.a., meningitis and otitis, contain both capsular and lipopolysaccharide surface antigens. The syntheses of several oligosaccharides corresponding to native H. influenzae polysaccharide structures is outlined with an emphasis on synthetically challenging features. Hence, the synthesis of a branched inner core lipopolysaccharide tetrasaccharide structure, α- l, d-Hep p-(1∅3)-[β- d-Glc p-(1∅4)]-α- l, d-Hep p-(1∅5)-αKdo, containing the unusual higher carbon sugars l- glycero- d- manno-heptose and Kdo is described, as well as the assembly of di- and trimers of the repeating unit of the capsular polysaccharides of serotype c,[−4)-3-OAc-β- d-Gl cpNAc-(1∅3)-α- d-Gal p-(1-PO − 3−] and serotype f[−3)-β- d-Gal pNAc-(1∅4)-3-OAc-α- d-Gal pNAc-(1-PO − 3], both linked via anomeric phospodiester linkages. Also efforts towards the synthesis of the repeating unit of the capsular polysaccharide of serotype e,∅3)-β- d-Gl cpNAc-(1∅4)-[β- d-Fru f-(2∅3)]-β- d-Man pNAcA-(1∅, containing a β-fructofuranosidic residue, is discussed. All synthetic derivates are spacer-equipped to allow formation of glycoconjugates for biological applications.