Henry E M, Kini G D, Larson S B, Robins R K, Alaghamandan H A, Smee D F
ICN Nucleic Acid Research Institute, Costa Mesa, California 92626.
J Med Chem. 1990 Aug;33(8):2127-30. doi: 10.1021/jm00170a013.
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.
利用三氯嘌呤环系中2-、6-和8-位对亲核取代反应活性的差异，将2,6,8-三氯-7-甲基嘌呤（3）转化为2-氯-8,9-二氢-7-甲基-8-硫代氧嘌呤-6(1H)-酮（5）。随后，根据Vorbrüggen方法，化合物5与1-O-乙酰基-2,3,5-三-O-苯甲酰基-D-呋喃核糖进行糖基化反应，得到2-氯-8,9-二氢-7-甲基-9-(2,3,5-三-O-苯甲酰基-β-D-呋喃核糖基)-8-硫代氧嘌呤-6(1H)-酮（6）。去除苯甲酰保护基，然后在150℃下用液氨对7进行胺化反应，得到7,8-二氢-7-甲基-8-硫代鸟苷（2）。通过X射线晶体学分析确定了化合物2的结构。对化合物1（7,8-二氢-7-甲基-8-氧代鸟苷）和2在各种动物病毒感染模型中的活性进行了评估。在小鼠中，针对班齐病毒、Semliki森林病毒和圣安杰洛病毒，在病毒接种前给药时，2具有高活性。
