Abstract
4′-Fluoro-2′,3′-O-isopropylidenecytidine was synthesized by the treatment of 5′-O-acetyl-4′-fluoro-2′,3′-O-isopropylideneuridine with triazole and 4-chlorophenyl dichlorophosphate followed by ammonolysis. The interaction of 4′-fluoro-2′,3′-O-isopropylidenecytidine with hydroxylamine resulted in 4′-fluoro-2′,3′-O-isopropylidene-5′-O-acetyl-N 4-hydroxycytidine. The removal of the 2′,3′-O-isopropylidene groups led to acetyl derivatives of 4′-fluorouridine, 4′-fluorocytidine, and 4′-fluoro-N 4-hydroxycytidine. 4′-Fluorouridine 5′-O-triphosphate was obtained in three steps starting from 4′-fluoro-2′,3′-O-isopropylideneuridine. 4′-Fluorouridine 5′-O-triphosphate was shown to be an effective inhibitor of HCV RNA-dependent RNA polymerase and a substrate for the NTPase reaction catalyzed by the HCV NS3 protein, the hydrolysis rate being similar to that of ATP. It could also activate a helicase reaction with an efficacy of only threefold lower than that for ATP.
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Abbreviations
- 4-ClPhOPOCl2 :
-
4-chlorophenyl dichlorophosphate
- NTP:
-
nucleoside 5′-O-triphosphate
- TEAB:
-
triethylammonium bicarbonate
- PBS:
-
phosphate buffered saline
- HCV:
-
hepatitis C virus
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Original Russian Text © M.A. Ivanov, G.S. Ludva, A.V. Mukovnya, S.N. Kochetkov, V.L. Tunitskaya, L.A. Alexandrova, 2010, published in Bioorganicheskaya Khimiya, 2010, Vol. 36, No. 4, pp. 526–534.
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Ivanov, M.A., Ludva, G.S., Mukovnya, A.V. et al. Synthesis and biological properties of pyrimidine 4′-fluoronucleosides and 4′-fluorouridine 5′-O-triphosphate. Russ J Bioorg Chem 36, 488–496 (2010). https://doi.org/10.1134/S1068162010040072
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DOI: https://doi.org/10.1134/S1068162010040072