Synthesis of phosphonate derivatives of 2'-deoxy-2'-fluorotetradialdose d-nucleosides and tetradialdose d-nucleosides

Tomáš Lášek; Juraj Dobiáš; Miloš Buděšínský; Jaroslav Kozák; Barbora Lapuníková; Ivan Rosenberg; Gabriel Birkuš; Ondřej Páv

doi:10.1016/j.tet.2021.132159

Synthesis of phosphonate derivatives of 2'-deoxy-2'-fluorotetradialdose d-nucleosides and tetradialdose d-nucleosides

Tetrahedron. 2021 Jun 4:89:132159. doi: 10.1016/j.tet.2021.132159. Epub 2021 Apr 16.

Authors

Tomáš Lášek^{1

2}, Juraj Dobiáš¹, Miloš Buděšínský¹, Jaroslav Kozák¹, Barbora Lapuníková¹, Ivan Rosenberg¹, Gabriel Birkuš¹, Ondřej Páv¹

Affiliations

¹ IOCB Prague, Flemingovo Nám. 2, 160 00, Prague, Czech Republic.
² UCT Prague, Technická 5, 166 28, Prague, Czech Republic.

Abstract

Analogs of nucleosides and nucleotides represent a promising pool of potential therapeutics. This work describes a new synthetic route leading to 2'-deoxy-2'-fluorotetradialdose D-nucleoside phosphonates. Moreover, a new universal synthetic route leading to tetradialdose d-nucleosides bearing purine nucleobases is also described. All new compounds were tested as triphosphate analogs for inhibitory potency against a variety of viral polymerases. The fluorinated nucleosides were transformed to phosphoramidate prodrugs and evaluated in cell cultures against various viruses including influenza and SARS-CoV-2.

Keywords: 2′-Fluoronucleoside; Nucleoside phosphonate; Prodrug; Tetradialdose d-nucleoside; Triphosphate.