Synthesis and anti-HIV and anti-HBV activities of 2'-fluoro-2',3'- unsaturated L-nucleosides

Kyeong Lee, Yongseok Choi, Elizabeth Gullen, Susan Schlueter-Wirtz, Raymond F. Schinazi, Yung Chi Cheng, Chung K. Chu

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

The synthesis of L-nucleoside analogues containing 2'-vinylic fluoride was accomplished by direct condensation method, and their anti-HIV and anti- HBV activities were evaluated in vitro. The key intermediate 8, the sugar moiety of our target compounds, was prepared from 1,2-O-isopropylidene-L- glyceraldehyde via (R)-2-fluorobutenolide intermediate 5 in five steps. Coupling of the acetate 8 with the appropriate heterocycles (silylated uracil, thymine, N4-benzoylcytosine, N4-benzoyl-5-fluorocytosine, 6- chloropurine, and 6-chloro-2-fluoropurine) in the presence of Lewis acid afforded a series of 2'-fluorinated L-nucleoside analogues (15-18, 23-26, 36- 45). The newly synthesized compounds were evaluated for their antiviral activities against HIV-1 in human peripheral blood mononuclear (PBM) cells and HBV in 2.2.15 cells. Cytosine 23, 5-fluorocytosine 25, and adenine 36 derivatives exhibited moderate to potent anti-HIV (EC50 0.51, 0.17, and 1.5 μM, respectively) and anti-HBV (EC50 0.18, 0.225, and 1.7 μM, respectively) activities without significant cytotoxicity up to 100 μM in human PBM, Vero, CEM, and HepG2 cells.

Original languageEnglish
Pages (from-to)1320-1328
Number of pages9
JournalJournal of Medicinal Chemistry
Volume42
Issue number7
DOIs
StatePublished - 8 Apr 1999

Fingerprint

Dive into the research topics of 'Synthesis and anti-HIV and anti-HBV activities of 2'-fluoro-2',3'- unsaturated L-nucleosides'. Together they form a unique fingerprint.

Cite this