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

2'-脱氧-2'-氟四二醛 d-核苷和四二醛 d-核苷的膦酸酯衍生物的合成

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

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.

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