Synthetic Access to Fluorinated Analogs of a Known Streptococcus pneumoniae Type 14 Glycotope

For the first time, we present fluorinated analogs of Streptococcus pneumoniae serotype 14 (SPn14)-specific tetrasaccharide antigens originating from the repeating unit {6)-[β-d-Galp-(1→4)-]-β-d-GlcpNAc-(1→3)-β-d-Galp-(1→4)-β-d-Glcp-(1→} _n of the capsule's outer cell surface, featuring different strategic fluorination sites. These modified pneumococcal tetrasaccharides are also equipped with allyl groups at the reducing end to enable further functionalization. Key transformation steps during the synthesis of these target molecules included (1 + 1)-glycosylations of fluorinated galactosyl donors as well as late fluorination steps, which were selectively performed on lactosyl building blocks. The subsequent central (2 + 2) couplings of the lactosyl donors with the respective lactosaminyl building blocks proceeded with good yields, enabling the synthesis of the desired target tetrasaccharide antigen analogs in amounts sufficient for future biological investigations following a global deprotection protocol. A total of six novel F-analogs of the SPn14 glycotope were produced using the methods described herein.