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

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

SUBMITTER: Michailidou F

PROVIDER: S-EPMC7728060 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Michailidou Freideriki F Lebl Tomas T Slawin Alexandra M Z AMZ Sharma Sunil Vishnuprasadji SV Brown Murray J B MJB Goss Rebecca Jane Miriam RJM

Molecules (Basel, Switzerland) 20201125 23

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'-d ...[more]

PMID: 33255573

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