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

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.

SUBMITTER: Lasek T

PROVIDER: S-EPMC8049856 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Lášek Tomáš T Dobiáš Juraj J Buděšínský Miloš M Kozák Jaroslav J Lapuníková Barbora B Rosenberg Ivan I Birkuš Gabriel G Páv Ondřej O

Tetrahedron 20210416

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 pho ...[more]

PMID: 33879930

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