The Gram-positive bacterium Streptococcus pneumoniae causes severe disease
globally. Vaccines that prevent S. pneumoniae infections induce antibodies
against epitopes within the bacterial capsular polysaccharide (CPS). A better
immunological understanding of the epitopes that protect from bacterial
infection requires defined oligosaccharides obtained by total synthesis. The
key to the synthesis of the S. pneumoniae serotype 12F CPS hexasaccharide
repeating unit that is not contained in currently used glycoconjugate vaccines
is the assembly of the trisaccharide
β-D-GalpNAc-(1→4)-[α-D-Glcp-(1→3)]-β-D-ManpNAcA, in which the branching points
are equipped with orthogonal protecting groups. A linear approach relying on
the sequential assembly of monosaccharide building blocks proved superior to a
convergent [3 + 3] strategy that was not successful due to steric constraints.
The synthetic hexasaccharide is the starting point for further immunological
investigations