Synthesis of Several Pyrimidine L-Nucleoside Analogues as Potential Antiviral Agents

Article abstract of DOI:10.1016/0040-4020(94)00997-9

β-L-5-Iodo-2'-deoxyuridine (β-L-IUdR, 7) and 1-<(β-L-arabinofuranosyl)-E-5-(2-bromovinyl)>uracil (β-L-BV-ara-U, 10) have been synthesized via a multi-step synthesis from L-arabinose. 2',3'-Dideoxy-β-L-5-azacytidine (18), 2',3'-dideoxy-β-L-2-thiocytidine (20) and their respective α-anomers, compounds 19 and 21, also were synthesized by direct coupling of 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (13) with the corresponding silylated bases, in the presence of EtAlCl2 in CH2Cl2, followed by separation of the α- and β-isomers and deblocking of the 5'-protecting groups.In addition, 2',3'-dideoxy-β-L-5-fluorocytidine (34), a potent anti-HIV and anti-HBV agent, was synthesized by an alternative methodology from 2',3'-dideoxy-β-L-5-fluorouridine (31) via a 4-triazolylpyrimidinone intermediate.These L-nucleoside analogues were tested in vitro against HIV, HBV, HSV-1, and HSV-2.Among these compounds, 2',3'-dideoxy-β-L-5-azacytidine (18) was found to show significant activity against HBV in vitro at approximately the same level as 2',3'-dideoxy-β-D-cytidine (ddC), which is a known potent anti-HBV agent.