Synthesis and Conformational Analysis of Fluorinated Uridine Analogues Provide Insight into a Neighbouring-Group Participation Mechanism |
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Authors: | Freideriki Michailidou Tomas Lebl Alexandra M Z Slawin Sunil Vishnuprasadji Sharma Murray J B Brown Rebecca Jane Miriam Goss |
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Institution: | 1.EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK; (F.M.); (T.L.); (A.M.Z.S.); (S.V.S.);2.GlaxoSmithKline, Stevenage SG1 2NY, UK; |
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Abstract: | Fluorinated nucleoside analogues have attracted much attention as anticancer and antiviral agents and as probes for enzymatic function. However, the lack of direct synthetic methods, especially for 2′,3′-dideoxy-2′,3′-difluoro nucleosides, hamper their practical utility. In order to design more efficient synthetic methods, a better understanding of the conformation and mechanism of formation of these molecules is important. Herein, we report the synthesis and conformational analysis of a 2′,3′-dideoxy-2′,3′-difluoro and a 2′-deoxy-2′-fluoro uridine derivative and provide an insight into the reaction mechanism. We suggest that the transformation most likely diverges from the SN1 or SN2 pathway, but instead operates via a neighbouring-group participation mechanism. |
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Keywords: | nucleoside fluorine fluorination neighbouring-group participation mechanism |
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