Synthesis of the phosphono analogue of the dimeric subunit of Neisseria meningitidis type A capsular polysaccharide

The development of a glycoconjugate vaccine against N. meningitidis type A bacterium is greatly hampered by the chemical lability of the phosphodiester bridges joining the N-acetyl mannosamine repeating units of its capsular polysaccharide. We describe the first synthesis of the phosphonodisaccharide α-D-Man-pNAc-[1→ CH2-P(O)(O-)→ 6]-β-D-ManpNAc-(1→ O)(CH2)(3)NH2 as a stable analogue of the corresponding phosphate-bridged disaccharide. The key phosphonoester linkage is obtained by condensation of monosaccharide building blocks under Mitsunobu conditions. Moreover, the protected precursor of the target compound is suitably designed to allow further elongation and synthesis of higher oligomers.