Synthesis of saccharide precursors suitable for preparation of potential inhibitors of glycosyltransferases

Authors: Jana Jakubčinová 1    Marek Baráth 1   
1 Center for Glycomics, Institute of Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9, SK-845 38 Bratislava, Slovakia   
Year: 2017
Section: Organic, bioorganic and pharmaceutical chemistry, pharmacology
Abstract No.: 1537
ISBN: 978-80-972360-1-4

The biosynthesis of N- and O-linked complex oligosaccharides, glycoproteins or glycoconjugates involves the action of hundreds of different glycosyltransferases (GTs), the enzymes that catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules. The result of the reaction catalyzed by these type of enzymes is the formation of a new glycosidic linkage [13].

This contribution describes preparation of precursors of glycosyltransferase inhibitors as a possible element for treatment of large scale diseases based on errors in glycosylation. Based on the calculated structural features of transition state model, a new scaffold has been proposed. Basic structure consists of hexofuranose skeleton (fructose, tagatose, psicose) mimicking the donor part. Acceptor part is mimicked by different substituted thioglycosides  (methyl, ethyl, phenyl or benzyl), furthermore the leaving group (uridine diphosphate) is mimicked as well by corresponding esthers of phosphoric acid at C-1 position. Necessary negative charge is then obtained by hydrolysis.

We describe preparation of compound VI by sequential synthesis (in five synthetic steps) starting from compound I – benzyl-2-thio-α-D-fructofuranoside prepared in our laboratory [4]. These compounds represent suitable and stable precursors of model mimetics for the preparation of target compounds as a transition state inhibitors of glycosyltransferases. The structures of all compounds were confirmed by NMR spectral data and elemental analyses.

Acknowledgement. Financial support of this work by the Slovak Grant Agency (VEGA 2/0024/16) is gratefully appreciated.
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