Synthesis and antiviral evaluation of some β- l-2′,3′-dideoxy-5-chloropyrimidine nucleosides and pronucleotides

The synthesis and in vitro anti human immunodeficiency virus (HIV) and anti-hepatitis B virus (HBV) activities of some unnatural β- l-nucleoside enantiomers related to the anti-HIV compound 2′,3′-dideoxy-3′-fluoro-5-chlorouridine (β- d-3′Fdd5ClU) are reported. In contrast to β- d-3′Fdd5ClU, β- l-3′Fdd5ClU and the other l-congeners were devoid of significant anti-HIV effects, but β- l-2′,3′-dideoxy-5-chlorocytidine (β- l-dd5ClC) and β- l-2′,3′-dideoxy-3′-fluoro-cytidine (β- l-3′FddC) showed a distinct anti-HBV activity. Three mononucleoside phosphotriester derivatives with S-pivaloyl-2-thioethyl ( t-BuSATE) groups as biolabile phosphate protective groups were also synthesized. The bis( t-BuSATE) derivative of β- d-3′Fdd5ClU retained anti-HIV activity in thymidine kinase deficient (TK −) CEM cells.