A Convenient Synthesis of 2′-Deoxy-2-fluoroadenosine; a Potential Prodrug for Suicide Gene Therapy

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 [ddot]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.