Post Glycosylation Diversification (PGD): An Approach for Assembling Collections of Glycosylated Small Molecules

21 September 2018, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Many small molecule natural products with are adorned with a carbohydrate as part of their molecular structure that acts to mediate key interactions with the target, attenuate physicochemical properties, or both. Facile incorporation of a carbohydrate group on de novo small molecules would enable these valuable properties to be leveraged in the evaluation of focused compound libraries. Here we report a new approach for the synthesis of glycosylated small molecule libraries that puts the glycosylation early in the synthesis of library compounds. Functionalized aglycones subsequently participate in chemoselective diversification reactions distal to the carbohydrate. A number of desosaminyl glycosides were prepared from only a few starting glycosides, using click cycloadditions, acylations, and Suzuki couplings as diversification reactions. New compounds were characterized for their inhibition of bacterial protein translation, bacterial growth, and in a T-cell activation assay.

Keywords

library design strategy
synthesis
cycloaddition
Suzuki Reactions
acylation

Supplementary materials

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Title
ChemRxiv PGD-SI 2018
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