Total synthesis of the core tetrasaccharide of Neisseria meningitidislipopolysaccharide, a potential vaccine candidate for meningococcal diseases

Abstract

The first total synthesis of the core tetrasaccharide α-GlcNAc-(1 → 2)-α-Hep-(1 → 3)-α-Hep-(1 → 5)-α-Kdo of Neisseria meningitidis LPS is achieved in a convergent and stereocontrolled [2 + 2] approach, whereby heptose building blocks obtained by de novo synthesis were fine-tuned for the effective assembly of the 1 → 5 linked Hep-Kdo disaccharide. The synthetic strategy incorporates an α-linked spacer at the reducing end of the tetrasaccharide for use as a handle during subsequent conjugation to a carrier protein.