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Title: Synthesis of 3',4'-difluoro-3'-deoxyribonucleosides and its evaluation of the biological activities: Discovery of a novel type of anti-HCV agent 3',4'-difluorocordycepin
Authors: Shimada, Hisashi ×
Haraguchi, Kazuhiro
Hotta, Kumi
Miyaike, Tomoko
Kitagawa, Yasuyuki
Tanaka, Hiromichi
Kaneda, Ryutaro
Abe, Hiroshi
Shuto, Satoshi
Mori, Kyoko
Ueda, Youki
Kato, Nobuyuki
Snoeck, Robert
Andrei, Graciela
Balzarini, Jan #
Issue Date: Nov-2014
Publisher: Pergamon
Series Title: Bioorganic & Medicinal Chemistry vol:22 pages:6174-6182
Article number: S0968-0896(14)00611-7
Abstract: Upon reacting 3',4'-unsaturated cytosine (8 and 9) and adenine nucleosides (13 and 14) with XeF2/BF3·OEt2, the respective novel 3',4'-difluoro-3'-deoxyribofuranosyl nucleosides (10-12 and 15-18) could be obtained. Formation of anti-adducts (11, 16 and 18) revealed that the fluorination involved oxonium ions as incipient intermediates. TBDMS-protected 3',4'-unsaturated adenosine provided the β-face adducts as sole stereoisomers whereas α-face-selectivity was observed with the TBDPS-protected adenosine 14. The evaluation of the novel 3'-deoxy-3',4'-difluororibofuranosylcytosine-(19-21) and adenine nucleosides (22-25) against antitumor and antiviral activities revealed that 3',4'-difluorocordycepin (24) was found to possess anti-HCV activity. The SI of 24 was comparable to that of the anti-HCV drug ribavirin. However, sofosbuvir, FDA-approved novel anti-HCV drug, showed better SI value. Our finding revealed that the introduction of the fluoro-substituent into the 4'-position of cordycepin derivatives decreased the cytotoxicity to the host cell with retention of the antiviral activity.
URI: 
ISSN: 0968-0896
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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