Chemoselectivity of 3,3'-dithiobis(sulfosuccinimylpropionate)-based 3-mercaptopropionylation of amine-linked aminomonosaccharides

Abstract

Many polysaccharides on the surface of bacteria contain free amino groups, limiting the application of amine-based linker in these glycans. Herein, we investigated the chemoselectivity of N-acylation during the dithiobis(sulfosuccinimidylpropionate)-based 3-mercaptopropionylation of amine-linked aminomonosaccharides. Interestingly, for the 2-, 3-, and 4-aminoglucosides and 4-aminogalactoside, the 3-mercaptopropionyl group was selectively installed onto the amine of the linker. The chemoselectivity for the introduction of the thiol moiety was poor with the 2- and 3-aminogalactosides and 2- and 3-aminomannosides. In the meanwhile, the Fukui function was used to further quantify the nucleophilicity of amino groups. These results will serve well for the preparation of conjugation-ready aminoglycans.