Synthesis and antiviral evaluation of some beta-L-2 ',3 '-dideoxy-5-chloropyrimidine nucleosides and pronucleotides

The synthesis and in vitro anti human immunodeficiency virus (HTV) and anti -hepatitis B virus (HBV) activities of some unnatural beta-L-nucleoside ena ntiomers related to the anti-HIV compound 2',3'-dideoxy-3'-fluoro-5-chlorou ridine (beta-D-3'Fdd5CIU) are reported. In contrast to beta-D-3'Fdd5ClU, be ta-L-3'Fdd5ClU and the other L-congeners were devoid of significant anti-HI V effects, but beta-L-2',3'-dideoxy-5-chlorocytidine (beta-L-dd5ClC) and be ta-L-2'-3'-dideoxy-3'-fluoro-cytidine (beta-L-3'FddC) showed a distinct ant i-HBV activity. Three mononucleoside phosphotriester derivatives with S-piv aloyl-2-thioethyl (t-BuSATE) groups as biolabile phosphate protective group s were also synthesized. The bis(t-BuSATE) derivative of beta-D-3'Fdd5ClU r etained anti-HIV activity in thymidine kinase deficient (TK-) CEM cells. (C ) 2000 Elsevier Science B.V. All rights reserved.