Issue 1, 2008

Synthesis of gem-difluorinated nucleoside analogues of the liposidomycins and evaluation as MraY inhibitors

Abstract

Two gem-difluoromethylenated nucleoside moieties of liposidomycins, 3 and 4, were designed and synthesized. Compound 3 was assembled from lactol5 and gem-difluoromethylenated nucleoside6. In the synthesis of target molecule 4, the coupling of the trichloroacetimidate derivative of gem-difluoromethylenated furanose7 with nucleoside8 in the presence of TMSOTf gave the unexpected compound 16 when CH3CN was used as solvent. This results from acetonitrile acting as a nucleophile and participating in the glycosylation reaction. This unusual process may be correlated with the presence of the electron-withdrawing gem-difluoro substituents at the C-2 position of furanose. Compound 3 demonstrated 29% inhibition of MraY at 11.4 mM.

Graphical abstract: Synthesis of gem-difluorinated nucleoside analogues of the liposidomycins and evaluation as MraY inhibitors

Supplementary files

Article information

Article type
Paper
Submitted
24 Aug 2007
Accepted
30 Oct 2007
First published
16 Nov 2007

Org. Biomol. Chem., 2008,6, 157-161

Synthesis of gem-difluorinated nucleoside analogues of the liposidomycins and evaluation as MraY inhibitors

X. Xu, A. E. Trunkfield, T. D. H. Bugg and F. Qing, Org. Biomol. Chem., 2008, 6, 157 DOI: 10.1039/B713068F

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