Synthesis and broad-spectrum antiviral activity of 7,8-dihydro-7-methyl-8-thioxoguanosine

2,6,8-Trichloro-7-methylpurine (3) was converted to 2-chloro-8,9-dihydro-7-methyl-8-thioxopurin-6(1H)-one (5) by utilizing the difference in reactivity of the 2-, 6-, and 8-positions in the trichloropurine ring system to nucleophilic displacement. Compound 5 was subsequently glycosylated with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose according to the Vorbrüggen procedure to yield 2-chloro-8,9-dihydro-7-methyl-9-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosy l)-8- thioxopurin-6(1H)-one (6). Removal of the benzoyl protecting groups, followed by amination of 7 with liquid ammonia at 150 degrees C, gave 7,8-dihydro-7-methyl-8-thioxoguanosine (2). The structure of compound 2 was confirmed by X-ray crystallographic analysis. Compounds 1 (7,8-dihydro-7-methyl-8-oxoguanosine) and 2 were evaluated for activity in various animal virus infection models. Against banzi, Semliki Forest, and San Angelo viruses in mice, 2 was highly active when administered before virus inoculation.