REGIOSELECTIVE 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'-dide oxy-3'-fluoro nucleosides are reported. Carbocyclic 2',3'-dideoxy-3'-f luoro nucleosides were obtained from the 3-fluoro cyclopentane derivat ive 4, which was prepared by two methods. The SN2-displacement of the hydroxyl group of(+/-)-(1 beta,2 alpha,3 beta,4 a)-4-acetamido-2-fluor o-3-hydroxycyclopentylmethyl acetate (1) with Ph(3)P-I-2 followed by t in hydride reduction afforded the 3-fluoroamino alcohol derivative 3. Alternatively, the protected fluoroamino alcohol 3 was prepared by reg io- and stereoselective bromo-fluorination of cis-4 beta-acetamidocycl opent-2-enemethyl acetate (5) with hydrogen fluoride-pyridine/N-bromos uccinimide followed by tin hydride reduction to remove the bromine ato m. Carbocyclic 2',3'-dideoxy-3'-fluoroguanosine (14) thus obtained was moderately active against herpes simplex virus in vitro.