Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate |
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| Authors: | Nadege Hamon Maurizio Quintiliani Jan Balzarini Christopher McGuigan |
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| Institution: | 1. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK;2. Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium |
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| Abstract: | We report in this Letter the synthesis of prodrugs of 2-fluoro-2-deoxyarabinose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate. We demonstrate the difficulty of realising a phosphorylation step on the anomeric position of 2-deoxyribose, and we discover that introduction of fluorine atoms on the 2 position of 2-deoxyribose enables the phosphorylation step: in fact, the stability of the prodrugs increases with the degree of 2-fluorination. Stability studies of produgs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate in acidic and neutral conditions were conducted to confirm our observation. Biological evaluation of prodrugs of 2,2-difluoro-2-deoxyribose-1-phosphate for antiviral and cytotoxic activity is reported. |
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| Keywords: | Sugars Deoxyribose Phosphorylation Prodrugs Fluorination |
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