Regio‐ and Stereoselective Synthesis of Carbocyclic 2′,3′‐Dideoxy‐3′‐ fluoro Nucleosides as Potential Antiviral Agents.

The synthesis and antiviral activity of racemic carbocyclic 2', 3'-dideoxy-3'-fluoro nucleosides are reported. Carbocyclic 2', 3'-dideoxy-3'-fluoro nucleosides were obtained from the 3-fluoro cyclopentane derivative 4, which was prepared by two methods. The SN2-displacement of the hydroxyl group of (±)-(1β, 2α, 3β, 4β)-4-acetamido-2-fluoro-3-hydroxycyclopentylmethyl acetate (1) with Ph3P-I2 followed by tin hydride reduction afforded the 3-fluoroamino alcohol derivative 3. Alternatively, the protected fluoroamino alcohol 3 was prepared by regio- and stereoselective bromo-fluorination of cis-4β-acetamidocyclopent-2-enemethyl acetate (5) with hydrogen fluoridepyridine/N-bromosuccinimide followed by tin hydride reduction to remove the bromine atom. Carbocyclic 2', 3'-dideoxy-3'-fluoroguanosine (14) thus obtained was moderately active against herpes simplex virus in vitro.