Synthesis and antiviral activity of the carbocyclic analogs of 5-ethyl-2'-deoxyuridine and of 5-ethynyl-2'-deoxyuridine

Abstract
The carbocyclic analogue of the antiviral agent 5-ethyl-2''-deoxyuridine (EDU) was synthesized by two routes. The pivotal step in the first route is the reaction of lithium dimethylcuprate with the carbocyclic analogue of 5-(bromomethyl)-2''-deoxyuridine dibenzoate (6). The second route is based on the synthesis of the carbocyclic analogue of 5-ethynyl-2''-deoxyuridine (12) by a coupling reaction catalyzed by bis(triphenylphosphine)palladium(II) chloride and copper(I) iodide, a method reported recently (Robins and Barr) for the synthesis of the true nucleoside 5-ethynyl-2''-deoxyuridine (1b). The carbocyclic analogue of EDU inhibits the replication of type 1 and type 2 herpes simplex viruses in Vero cells. The carbocyclic analogue of 5-ethynyl-2''-deoxyuridine has modest activity against herpes simplex virus, types 1 and 2.