Synthesis and Characterization of 3'-Deoxy-3'-fluoro-2'-O,3'-C-vinylene Linked Bicyclic Uridine†

doi:10.7503/cjcu20130395

Abstract

Abstract:

Synthesis of conformationally restricted nucleosides and oligonucleotides has received much attention in recent years. Moreover, it has been demonstrated that most nucleosides with fluorine in the sugar moiety possess potent antitumor and/or antiviral activities. However, to the best of our knowledge, there are few reports on conformationally restricted nucleosides with fluorinated sugar moiety. Herein, we report the design and synthesis of a novel fluorinated bicyclic nucleoside, 3'-deoxy-3'-fluoro-2'-O,3'-C-vinylene linked bicyclic uridine, via an eleven-step synthesis from D-xylose. The synthetic route involved ethynylation in the sugar ring, diethylaminosulphur trifluoride(DAST)-mediated fluorination and configuration inversion at the 3'-position to give the key intermediate 7, which then coupled with nucleobase, followed by deprotection and ring closure under basic conditions to afford the target compound 1. Its structure was characterized by ¹H NMR, ¹³C NMR and HRMS. A plausible mechanism for the formation of the key intermediate 7 was proposed. It could be rationalized by the neighbouring group participation of the 3-benzoate ester and the generation of the benzoxonium ion B. The present work provides an efficient tool for the construction of biologically interesting fluorinated bicyclic nucleosides and their analogues.

Key words: Fluoro, Ethynyl group, Bicyclic nucleoside, Uridine

CLC Number:

TrendMD:

ZHAO Baojuan, YU Wenquan, CHANG Junbiao, LI Ertong, DING Qunshan, LI Fengjuan, CHEN Guangying, WANG Na. Synthesis and Characterization of 3'-Deoxy-3'-fluoro-2'-O,3'-C-vinylene Linked Bicyclic Uridine^†[J]. Chem. J. Chinese Universities, 2014, 35(1): 58.

Figures/Tables 3

References 21

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