Uses
2''-Deoxy-2''-fluoroguanosine, can be used as powerful tool for structural manipulation of G-quadruplexes. It is also a influenza viral polymerase inhibitor like Ribavirin (R414475), used as a antiviral drug against avian (H5N1) influenza virus.
Definition
2'-Deoxy-2'-fluoroguanosine is an analog of guanosine that inhibits the viral life cycle. It is a competitive inhibitor of the viral transcriptase enzyme, which prevents RNA synthesis and subsequent protein synthesis. 2'-Deoxy-2'-fluoroguanosine has been shown to inhibit the growth of wild-type viruses in cell culture and to be effective against resistant mutants in cell culture. This drug has also been shown to inhibit the replication of herpes simplex virus type 1 (HSV-1) and influenza virus type A/WSN/33 (H1N1) in cell culture, as well as inhibiting the production of rna from these viruses.
Synthesis
The synthesis of 2'-deoxy-2'-fluoroguanosine was accomplished using tetraisopropyldisiloxanyl (TPDS) protected 9-beta-D-arabinofuranosylguanine as starting material, and conversion to the intermediate diisobutyryl-arabinofuranosylguanosine. Deprotection of the TPDS group, was followed by protection of the hydroxyl group with THP to give diisobutyryl di-THP protected arabinofuranosylguanine. Selective O-deacylation and triflation was followed by treatment of the crude product with fluoride, then deprotection of the THP groups.
References
[1] M. Ikehara, J. Imura. “Studies on Nucleosides and Nucleotides. LXXXVII. Purine Cyclonucleosides. XLII. Synthesis of 2’-Deoxy-2’-fluoroguanosine.” Chemical & pharmaceutical bulletin 22 1 (1981): 1034–1038.
[2] G V Zaitseva. “Chemical and enzymatic synthesis and antiviral properties of 2’-deoxy-2’-fluoroguanosine.” Nucleosides & nucleotides 18 4–5 (1999): 687–8.
[3] M Tisdale. “Inhibition of influenza virus transcription by 2’-deoxy-2’-fluoroguanosine.” Antimicrobial Agents and Chemotherapy 39 11 (1995): 2454–8.
