Design, synthesis, and biological evaluation of novel iso-d-2′,3′-dideoxy-3′-fluorothianucleoside derivatives

Novel iso-d-2′,3′-dideoxythianucleoside derivatives 1–4 were designed and asymmetrically synthesized as a bioisostere of lamivudine to search for new anti-HIV agents. The information about using sulfur participation occurred on DAST fluorination and Mitsunobu reaction will be of great help in synthesizing sulfur-containing compounds. Final compounds 1–4 were evaluated against HIV-1 and 2, HSV-1 and 2, EMCV, Cox. B3, VSV, FluA (Taiwan), FluA (Johan.), FCV, and FIP. Only cytosine analogue 3 showed a potent anti-VSV activity (EC(50) = 9.43 μg/mL). This result implies that iso-2′,3′-dideoxy sugar templates might play a role of a sugar surrogate of nucleosides for the development of anti-RNA virus agent.