Syntheses of propargyl glycosides of disaccharides of the capsular polysaccharides from serotypes 4, 7F, and 9V Streptococcus pneumoniae for glycoconjugate vaccines

Abstract

We have developed a means of presenting relatively small glycans in a context to make them T cell-dependent antigens. This approach requires synthesis of glycans that remain close to carrier proteins upon conjugation, allowing T cell recognition and generation of B cells that produce high-affinity antibodies and memory toward target pathogens. In this work, we describe the syntheses of three disaccharides of the capsular polysaccharides from serotypes 4, 7F and 9V Streptococcus pneumoniae (Sp) as propargyl glycosides for use in this vaccine strategy. While variations of these disaccharides have previously been synthesized, none have been synthesized with an alkyne as the linker. Incorporation of the alkyne led to redesign of the synthesis of each disaccharide. All three disaccharides were synthesized without use of benzyl protective groups, one of the most used carbohydrate protective groups due to its stability and ease of removal via hydrogenation. We report challenges that arose while synthesizing the targets with less common protective groups, such as naphthyl ethers, and the methods used to successfully overcome these challenges.