Synthesis of phosphorylated fragments of Streptococcus pneumoniae type 19F capsular polysaccharide

Serotype 19F is one of the most virulent of the Streptococcus pneumoniae serotypes, causing meningitis, otitis media, septicemia and pneumonia. Effective protection against infection is mediated by antibodies directed against its capsular polysaccharide (CPS), composed of the trisaccharide repeating units (→4-β-D-ManpNAc-(1→4)-α-D-Glcp-(1→2)-α-L- Rhap-1→) bridged by phosphate diesters. Unfortunately, CPSs are typical T-independent type 2 immunogens. Therefore, the conjugation of putative saccharide haptens to a protein carrier, which invokes T-cell involvement, has proved to be extremely effective in enhancing the immune response. In a project aimed at ascertaining the role played by the different structural factors in the immunogenicity of new vaccines against Streptococcus pneumoniae type 19F, we planned the synthesis of a family of trisaccharide repeating unit derivatives where the phosphate group is a) absent; b) linked only to the rhamnose unit; or c) linked only to the N-acetylmannosamine unit. Compound of type a) and c) also bear an appropriate spacer for conjugation to the protein carrier. Moreover, the synthesis of a dimer of the CPS repeating unit, in which a phosphate diester bridges two repeating units, was carried out.