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

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Xu, Xiu-Hua, Trunkfield, Amy E., Bugg, Tim and Qing, Feng-Ling. (2008) Synthesis of gem-difluorinated nucleoside analogues of the liposidomycins and evaluation as MraY inhibitors. Organic & Biomolecular Chemistry, Vol.6 (No.1). pp. 157-161. ISSN 1477-0520

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Abstract

Two gem-difluoromethylenated nucleoside moieties of liposidomycins, 3 and 4, were designed and synthesized. Compound 3 was assembled from lactol 5 and gem-difluoromethylenated nucleoside 6. In the synthesis of target molecule 4, the coupling of the trichloroacetimidate derivative of gem-difluoromethylenated furanose 7 with nucleoside 8 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.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH): Antiviral nucleosides -- Synthesis, Chemical inhibitors
Journal or Publication Title: Organic & Biomolecular Chemistry
Publisher: Royal Society of Chemistry
ISSN: 1477-0520
Official Date: 2008
Volume: Vol.6
Number: No.1
Number of Pages: 5
Page Range: pp. 157-161
Identification Number: 10.1039/b713068f
Status: Peer Reviewed
Publication Status: Published
Funder: Guo jia zi ran ke xue ji jin wei yuan hui (China) (NSFC), China. Jiao yu bu (China. Ministry of Education), Shanghai Municipal Scientific Committee
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URI: http://wrap.warwick.ac.uk/id/eprint/30876

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