Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lášek, Tomáš, Dobiáš, Juraj, Buděšínský, Miloš, Kozák, Jaroslav, Lapuníková, Barbora, Rosenberg, Ivan, Birkuš, Gabriel, Páv, Ondřej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049856/
https://www.ncbi.nlm.nih.gov/pubmed/33879930
http://dx.doi.org/10.1016/j.tet.2021.132159
Descripción
Sumario: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.