Fluorinated 7-Deazapurine 2′-Deoxyribonucleosides: Modification At The Nucleobase And The Sugar Moiety

Abstract

7-Deaza-7-fluoro-purine 2′-deoxynucleosides as well as 2′-deoxy-2′-fluoroarabinofuranosyl nucleosides 1–8 were synthesized. The fluorine atom was introduced on the base level with Selectfluor. Nucleobase-anion glycosylation was then employed to form the nucleosides. Properties of the fluorine compounds were studied in solution and in solid state. Compound 4a was incorporated into oligonucleotides where the stabilizing effect was observed.

Keywords:

• fluorination
• pyrrolo[2,3-d]pyrimidine
• glycosylation
• sugar conformation
• base pairing

Acknowledgments

We gratefully acknowledge financial support by Idenix Pharmaceuticals, Cambridge, USA.

Notes

^a Thermodynamic parameters are derived from the fitting of melting curves measured at 260 nm in 1 M NaCl, 100 mM MgCl₂, and 60 mM Na-cacodylate buffer, pH 7.0, with 5 μ M + 5 μ M single-strand concentration.

^b T _m values are given in °C. ^c Measured in 100 mM NaCl, 10 mM MgCl₂, and 10 mM Na-cacodylate buffer, pH 7.0, with 10 μ M single-strand concentration.