Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Hamon, Nadege¹  Quintiliani, Maurizio¹  Balzarini, Jan²  McGuigan, Christopher¹ 

[1] Cardiff Univ, Sch Pharm & Pharmaceut Sci, Cardiff CF10 3NB, S Glam, Wales

[2] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium

关键词: Sugars;    Deoxyribose;    Phosphorylation;    Prodrugs;    Fluorination;   

DOI  :  10.1016/j.bmcl.2013.02.117

来源: Elsevier

【 摘 要 】

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. (C) 2013 Published by Elsevier Ltd.

【 授权许可】

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