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Title: 5'-O-phosphonomethyl-2',3'-dideoxynucleosides: synthesis and anti-HIV activity
Authors: Jie, Liu
Van Aerschot, Arthur
Balzarini, Jan
Janssen, Gerardus
Busson, Roger
Hoogmartens, Jos
De Clercq, Erik
Herdewijn, Piet # ×
Issue Date: Sep-1990
Publisher: Amer Chemical Soc
Series Title: Journal of Medicinal Chemistry vol:33 issue:9 pages:2481-2487
Abstract: 5'-O-Phosphonomethylation of different pyrimidine 2',3'-dideoxynucleosides was accomplished by reaction of the latter with diethyl [(p-toylsulfonyl)oxy]methanephosphonate (1) in the presence of sodium hydride. The base-phosphonomethylated (15-19) and sugar-phosphonomethylated (8-12) derivatives could be readily distinguished by 1H and 13C NMR and MS analysis. Protection of the uracil or thymine residue with a N3-benzoyl group failed to prevent base modification. However, O4-methyl-protected 2',3'-dideoxyuridine readily afforded the 5'-O-phosphonomethylated derivative 12, which was converted to both the 2',3'-didoxyuridine analogue 27 and the 2',3'-dideoxycytidine counterpart 29. The 5'-O-phosphonomethyl derivatives of 3'-deoxythymidine (23), 2',3'-dideoxyuridine, (27), 2',3'-dideoxycytidine (29), 3'-O-methylthymidine (26), and 3'-amino-3'-deoxythymidine (28) did not show an appreciable anti-HIV activity in MT-4 cells. In contrast, the 5'-O-phosphonomethyl derivatives of 3'-deoxy-3'-fluorothymidine (24) and 3'-azido-3'-deoxythymidine (25) inhibited HIV-1 cytopathogenicity by 50% at a concentration of approximately 1 microM.
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
Laboratory of Virology and Chemotherapy (Rega Institute)
Pharmaceutical Analysis
× corresponding author
# (joint) last author

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