Synthesis and Conformational Analysis of Fluorinated Uridine Analogues Provide Insight into a Neighbouring-Group Participation Mechanism

Molecules

Freideriki Michailidou¹  Tomas Lebl¹  RebeccaJane Miriam Goss¹  SunilVishnuprasadji Sharma¹  AlexandraM. Z. Slawin¹  MurrayJ. B. Brown² 

[1] EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK;GlaxoSmithKline, Stevenage SG1 2NY, UK;

关键词: nucleoside;    fluorine;    fluorination;    neighbouring-group participation;    mechanism;   

DOI  :  10.3390/molecules25235513

来源: DOAJ

【 摘 要 】

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 S_N1 or S_N2 pathway, but instead operates via a neighbouring-group participation mechanism.

【 授权许可】

Unknown