Viktor Kelemen, Milán Csiszár, Anikó Borbás

Toward synthesis of thioglycosyl-phosphonate analogues of lipid ll

Introduction

Toward synthesis of thioglycosyl-phosphonate analogues of lipid ll. Explore the synthesis of novel thioglycosyl-phosphonate analogues of lipid II, targeting bacterial transglycosylases for new antibiotics. Features stereoselective photoinitiated thiol-ene addition.

Abstract

Section: Articles Keywords: synthesis, carbohydrate, lipid II, photoinitiated thiol-ene addition, Wadsworth-Horner-Emmons Although a multitude of epidemics have already been eradicated with the use of modern antibiotics, in the 20th century, a new and increasingly serious phenomenon has arisen - the resistance against antibiotic therapies, necessiting the need for the development of novel antibiotic compounds. Transglycosylases are key enzymes in the biosynthesis of the bacterial cell wall, and currently there is no approved drug in human use against them, so they are an excellent target for further antibiotic development. During our research, the main goal was to synthesize compounds that are structurally similar to lipid ll, the substrate of bacterial transglycosylases, however, with significant modifications, such as the incorporation of an α-thioglycosidic unit instead of the α-O-glycosidic bond and an alkylphosphonate unit instead of the pyrophosphate part, making the molecules suitable to act as enzyme inhibitors. The key step of our work is the stereoselective construction of the 1,2-cis-α-thioglycosidic bond by photoinitiated thiol ene coupling reaction. ln this paper, the novel synthesis route is described which can be applied to furnish different lipid ll analogues, on example synthesis of a D-glucose derivative.

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