Synthesis of L-Analogues of 1-(2′,3′-Dideoxy-β-D-glycero-pent-2-enofuranosyl)thymine

β-L(-)-2′,3′-Dideoxy-3′-thiacytidine (3TC), its 5-fluoro derivative ((—)-FTC), 2′,3′-dideoxycytidine (β-L-ddC), and its 5-fluoro derivative (β-L-FddC) have been reported to have anti-HIV and anti-HBV activity. It was of particular interest therefore to develop a series of β-L-d4T analogues bearing several kinds of amino-linker arms at the C-5 position of the pyrimidine moiety in an attempt to find more potent and less toxic anti-HIV agents. In addition, modification of nucleosides with various functional molecules has been attracting wide interest in biological studies since the primary amino groups could be useful for the attachment of either fluorescent dyes or a non-nucleosidic reverse transcriptase inhibitor. These modified nucleosides were evaluated for antiviral activity against HIV-1LAI in CEMSS cells and HIV-1IIIB in MT4 cells. Unfortunately, none of the compounds exhibited significant anti-HIV activity at the doses tested.