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.

Graphical Abstract

Keywords:

• Amino linker
• aminosuagr
• chemoselectivity
• 3,3'-dithiobis(sulfosuccinimidylpropionate)
• thiol linker

Supplemental material

Computational data and NMR spectra of synthetic compounds. This material is available free of charge via the Internet https://www.tandfonline.com/toc/lcar20/current.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the [National Natural Science Foundation of China] under Grant [number 22077052, 22277042], the [National Key R&D Program of China] under Grant [number 2020YFA0908304].