A convenient synthesis of 2'-deoxy-2-fluoroadenosine; a potential prodrug for suicide gene therapy

  • Nucleosides Nucleotides Nucleic Acids. 2000 Mar;19(3):559-65. doi: 10.1080/15257770008035007.
A E Hassan  1 ,  A T Shortnacy-Fowler ,  J A Montgomery ,  J A Secrist 3rd
Affiliations
  • 1. Drug Discovery Division, Southern Research Institute, Birmingham, AL 35255-5305, USA.
PMID: 10843492 DOI: 10.1080/15257770008035007
Abstract

A convenient synthesis of 2'-deoxy-2-fluoro-adenosine (1) is described. Deaminative fluorination of 2-aminoadenosine (2) followed by silylation of the 3', 5'-hydroxyl groups gave the corresponding 2-fluoroadenosine derivative 4 in good yield. Thiocarbonylation of 4 to thiocarbonylimidazolyl derivative 5a followed by treatment with an excess of tris(trimethylsilyl)silane (TTMSS) and tert-butyl peroxide in toluene at 80 degrees C was found to affect an efficient deoxygenation to the corresponding 2'-deoxy derivative 6. Desilylation of 6 by Et4NF in CH3CN afforded 1 in high yield.

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