Synthesis of brain-targeted 5-iodo-, 5-vinyl- and (E)-5-(2-iodovinyl)-2′-deoxyuridines coupled to a dihydropyridine ⇌ pyridinium salt redox chemical delivery system

5-Iodo-3′-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2′-deoxyuridine (15a) , 5-vinyl-3′-O-(1-methyl-1,4-di-hydropyridyl-3-carbonyl)-2′-deoxyuridine (15b) and (E)-5-(2-iodovinyl)-3′-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2′-deoxyuridine (15c) were synthesized for future evaluation as lipophilic brain-selective antiviral agents for the treatment of herpes simplex encephalitis. Quaternization of the 3′-O-(3-pyridylcarbonyl) compounds 10–11 using iodomethane afforded the corresponding 1-methylpyridinium salts 12–13 which were reduced with sodium dithionite to yield the corresponding 3′-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl) compounds 14–15.