Synthesis and antiviral evaluation of 2′, 2′, 3′, 3′-tetrafluoro nucleoside analogs. Issue 7 (15th February 2017)

• Record Type: Journal Article
• Authors: Sari, Ozkan; Bassit, Leda; Gavegnano, Christina; McBrayer, Tamara R.; McCormick, Louise; Cox, Bryan; Coats, Steven J.; Amblard, Franck; Schinazi, Raymond F.
• Is Part Of: Tetrahedron letters. Volume 58:Issue 7(2017)
• Page Start: 642
• Page End: 644
• Publication Date: 2017-02-15
• Subjects: Nucleoside -- Prodrug -- Antiviral -- Fluorine -- Mitsunobu; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2017.01.006
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: The synthesis of novel 2′, 2′, 3′, 3′-tetrafluoro nucleoside analogs is described. Glycosylation reactions are achieved via Mitsunobu coupling. Energetics of ring conformation are compared to differently substituted ribose. Evaluation of Tetrafluoro nucleosides in vitro against a panel of DNA and RNA viruses. Abstract: Herein, we report the synthesis of novel 2′, 2′, 3′, 3′-tetrafluorinated nucleoside analogs along with their phosphoramidate prodrugs. A tetrafluoro ribose moiety was coupled with different Boc/benzoyl-protected nucleobases under Mitsunobu conditions. After deprotection, tetrafluorinated nucleosides13b, 14b, 20b -22b were reacted with phenyl-(isopropoxy-l -alaninyl)-phosphorochloridate to afford corresponding monophosphate prodrugs24b –28b . All synthesized compounds were evaluated against several DNA and RNA viruses including HIV, HBV, HCV, Ebola and Zika viruses.