Synthesis and antiviral activity of fluoro-substituted apio dideoxynucleosides

Novel fluoro-substituted apio dideoxynucleosides ((+/-)-3a and (+/-)-3b) were efficiently synthesized starting from 1,3-dihydroxyacetone via Horner-Emmons olefination as a key step. Cyclization of fluoro ester (+/-)-6 under acidic conditions to the fluorolactone was smoothly proceeded in favor of trans-fluorolactone due to the favorable transition state with equatorial hydroxymethyl substituent. Unfortunately, the final nucleosides (+/-)-3a and (+/-)-3b were found to be inactive against several viruses such as HIV-1, HSV-1, HSV-2 and HCMV.