Synthesis of Novel Fluorinated 2′,3′-Dideoxynucleosides (original) (raw)

Nucleosides & nucleotides

The synthesis of various 2′,3′-dideoxypyrimidine nucleosides, starting from 5-(2,2,2-trifluoroethoxymethyl) (10) and 5-(bis-2,2,2-trifluoroethoxy)methyl-2′-deoxyuridine (11), is described. These compounds were synthesized for screening against herpes simplex virus type-1 and type-2, and HIV virus.

Synthesis and antiviral evaluation of 2',2',3',3'-tetrafluoro nucleoside analogs

Tetrahedron letters, 2017

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 nucleosides 13b, 14b, 20b-22b were reacted with phenyl-(isopropoxy-L-alaninyl)-phosphorochloridate to afford corresponding monophosphate prodrugs 24b-28b. All synthesized compounds were evaluated against several DNA and RNA viruses including HIV, HBV, HCV, Ebola and Zika viruses.

Synthesis of 4′-Substituted-2′-Deoxy-2′-α-Fluoro Nucleoside Analogs as Potential Antiviral Agents

Molecules

Nucleoside analogs are widely used for the treatment of viral diseases (Hepatitis B/C, herpes and human immunodeficiency virus, HIV) and various malignancies. ALS-8176, a prodrug of the 4′-chloromethyl-2′-deoxy-2′-fluoro nucleoside ALS-8112, was evaluated in hospitalized infants for the treatment of respiratory syncytial virus (RSV), but was abandoned for unclear reasons. Based on the structure of ALS-8112, a series of novel 4′-modified-2′-deoxy-2′-fluoro nucleosides were synthesized. Newly prepared compounds were evaluated against RSV, but also against a panel of RNA viruses, including Dengue, West Nile, Chikungunya, and Zika viruses. Unfortunately, none of the compounds showed marked antiviral activity against these viruses.

D-and L-2', 3'-didehydro-2', 3'-dideoxy-3'-fluoro-carbocyclic nucleosides: Synthesis, anti-HIV activity and mechanism of resistance

Journal of medicinal …, 2007

The structures of several potent NRTIs, such as stavudine (d4T), abacavir, reverset (d-d4FC), and elvucitabine (l-d4FC) highlight the important role of a 2',3'-double bond to enhance the antiviral activity (Figure 1). 1 Additionally, carbocyclic nucleosides such as abacavir ...

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