Synthesis and biological activity of 5-(2,2-difluorovinyl)-2'-deoxyuridine

5-(2,2-Difluorovinyl)uracil (IV) was synthesized from 2,4-dimethoxy-5-bromopyrimidine by sequential formylation, difluoromethylenation, and removal of the 2- and 4-methyl groups. Condensation of the trimethylsilyl derivative of IV with protected D-erythro-pentofuranosyl chloride followed by separation of anomers and deblocking gave 5-(2,2-difluorovinyl)-2'-deoxyuridine (V). Compound V was active against herpes simplex virus type 1 (HSV-1) infection as well as tumor cells transformed by the HSV-1 thymidine kinase gene.