title: Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate.
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.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
authors.forename: Nadege
authors.initials: N
authors.lastname: Hamon
authors.forename: Maurizio
authors.initials: M
authors.lastname: Quintiliani
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Christopher
authors.initials: C
authors.lastname: McGuigan
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003854:Deoxyribonucleotides / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D051379:Mice; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D012267:Ribosemonophosphates / Q000737:chemistry*; D018139:Simplexvirus / Q000187:drug effects; D014616:Vaccinia virus / Q000187:drug effects; D018116:Vesiculovirus / Q000187:drug effects
chemical_list: C583903:2,2-difluoro-2-deoxyribose-1-phosphate; C583902:2-fluoro-2-deoxyribose-1-phosphate; D000998:Antiviral Agents; D003854:Deoxyribonucleotides; D011355:Prodrugs; D012267:Ribosemonophosphates; C031302:2-deoxyribose 1-phosphate
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