Synthesis And Conformational Analysis Of Fluorinated Uridine Analogues Provide Insight Into A Neighbouring-Group Participation Mechanism

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(N)1 or S(N)2 pathway, but instead operates via a neighbouring-group participation mechanism.