Regio- and Stereoselective Synthesis of Carbocyclic 2’,3’-Dideoxy-3’-fluoro Nucleosides as Potential Antiviral Agents

Abstract

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-fluoro amino 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 fluoride-pyridine/ 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. © 1994, The Pharmaceutical Society of Japan. All rights reserved.