Simple Synthesis of Sulfonyl Amidine-Containing Glucosidase Inhibitors by a Chemoselective Coupling Reaction Between D-Gluconothiolactam and Sulfonyl Azides

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Muhammad Aswad
Junya Chiba
Takenori Tomohiro
Yasumaru Hatanaka

Abstract

In this report, we describe a simple synthesis of gluconoamidinylsulfones as a new class of potential inhibitors toward glycan processing enzymes. Gluconoamidinylsulfones have a glucose-based sulfonyl amidine skeleton, thus would form a distorted half-chair conformation with positive charge, which is analogous to transition state in the enzymatic process. A chemoselective coupling reaction between thioamide and sulfonyl azide enabled one-step synthesis of the iminosugar derivatives from commercially available D-gluconothiolactam in a protection-free manner. The phenyl-substituted gluconoamidinylsulfone displayed high inhibitory ability toward a- and b-glucosidases with Ki values of 13.9 and 8.2 mM, respectively, resulting that gluconoamidinylsulfones would be expected to entry in a new class of promising potential inhibitors toward various glycan-processing enzymes.

Keywords:
Inhibitor, glycosidase, iminosugar, coupling reaction, one-step synthesis, thioamide, sulfonyl azide, gluconoamidinylsulfone

Article Details

How to Cite
Aswad, M., Chiba, J., Tomohiro, T., & Hatanaka, Y. (2017). Simple Synthesis of Sulfonyl Amidine-Containing Glucosidase Inhibitors by a Chemoselective Coupling Reaction Between D-Gluconothiolactam and Sulfonyl Azides. International Research Journal of Pure and Applied Chemistry, 14(2), 1-8. https://doi.org/10.9734/IRJPAC/2017/34259
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Short Research Article