NUCLEOSIDES AND NUCLEOTIDES .144. SYNTHESIS AND ANTIVIRAL ACTIVITY OF5-SUBSTITUTED (2'S)-2'-DEOXY-2'-C-METHYLCYTIDINES AND (2'S)-2'-DEOXY-2'-C-URIDINES

Synthesis of several 5-substituted (2'S)-2'-deoxy-2'-C-methyl-cytidine s (8) and -uridines (6,11) has been accomplished using radical deoxyge nation of the 2'-tert-alcohols via their methyl oxalyl esters as a key reaction. Anti-herpes simplex virus type-1 and -2, and anti-varicella -zoster virus activities of the newly synthesized nucleosides were eva luated. Among them, the 5-iodouracil derivative 6e showed the most pot ent activity against herpes simplex virus type-1, with an EC(50) of 0. 14 mu g/mL without showing cytotoxicity up to 100 mu g/mL, but had a w eak activity against herpes simplex virus type-2 and no activity again st varicella-zoster virus up to 50 mu g/mL in vitro. Although the 5-fl uorocytosine derivative 8b had a potent anti-herpes simplex virus type -1 activity (EC(50) = 0.22 mu g/mL), it was rather cytotoxic to the CC RF-HSB-2 human T-cell line (IC50 greater than or equal to 1.0 mu g/mL) .