Saccharide precursors suitable for preparation of potential inhibitors of glycosyltransferases

Glycosyltransferases (GTs) are 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 [1-2].

This contribution describes preparation of precursors of glycosyltransferase inhibitors as a possible element for treatment of large scale diseases based on errors in glycosylation. Its course as well as changes in glycosylation have become the subject of various studies of scientific and pharmaceutical research.

Based on the calculated structural features of transition state model, a new scaffold has been proposed. Donor part is mimicking by hexofuranose skeleton (D-fructose, D-tagatose, D-psicose) and acceptor part is mimicked by different substituted thioglycosides  (methyl, ethyl, phenyl or benzyl). The leaving group (uridine diphosphate) is mimicked as well by corresponding esthers of phosphoric acid at C-1 position. Then is obtained negative charge by hydrolysis. These type enzymes required presence of metal co-factor (Mn²⁺ or Mg²⁺) [3].

We describe preparation of selected key intermediates and precursors of GTs inhibitors by sequential synthesis starting from benzyl-2-thio-α-D-fructofuranoside prepared in our laboratory [4]. The structures of all compounds were confirmed by NMR spectral data (¹H, ¹³C, COSY, HSQC, ³¹P) and elemental analyses.