Synthesis and biological evaluation of 1,3-oxathiolane 5-azapyrimidine, 6-azapyrimidine, and fluorosubstituted 3-deazapyrimidine nucleosides

(2R,5S)-5-Amino-2-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2,4-triazine-3( 2H)-one (8) and (2R,5R)-5-amino-2-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1 ,2,4-triazine-3(2H)-one (9) have been synthesized via a multi step procedur e from 6-azauridine. (2R,5S)-4-Amino-1-[2-(hydroxymethyl)-1, 3-oxathiolan-5 -yl]-1, 3, 5-triazine-2(1H)-one (11) and (2R,5R)-4-amino-1-[2-(hydroxymethy l)-1,3-oxathiolan-5-yl]-1,3,5-triazine-2(1H)-one (12), and the fluorosubsti tuted 3-deazanucleosides (19-24) have been synthesized by the transglycosyl ation of (2R,5S)-1-{2-[[(tert-butyldiphenylsilyl) oxy]methyl]-1,3-oxathiola n-5-yl}cytosine (2) with silylated 5-azacytosine and the corresponding sily lated fluorosubstituted 3-deazacytosines, respectively, in the presence of trimethylsilyl trifluoromethanesulfonate as the catalyst in anhydrous dichl oroethane, followed by deprotection of the blocking groups. These compounds were tested in vitro for cytotoxicity against L1210, B16F10, and CCRF-CEM tumor cell lines and for antiviral activity against HIV-1 and HBV.