Girgis N S, Michael M A, Smee D F, Alaghamandan H A, Robins R K, Cottam H B
ICN Nucleic Acid Research Institute, Costa Mesa, California 92626.
J Med Chem. 1990 Oct;33(10):2750-5. doi: 10.1021/jm00172a011.
C-Glycosylation of two guanine analogues, 9-deaza- and 7-deazaguanine, has been achieved under Friedel-Crafts conditions, providing a direct synthetic route to 9-deazaguanosine (4; 2-amino-7-beta-D-ribofuranosyl-5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one) and 8-beta-D-ribofuranosyl-7-deazaguanine (16), respectively. This electrophilic C-glycosylation was applied successfully to six guanine and substituted-guanine analogues resulting in yields of approximately 50%. This represents the first reported C-ribosylation of preformed nitrogen heterocycles isosteric with guanine. These C-nucleosides were evaluated for their ability to provide protection against a lethal Semliki Forest virus infection in mice, relative to 7-thia-8-oxoguanosine which was used as a positive control. Two of the C-nucleosides, 2-amino-6-chloro-5-methyl-7-beta-D-ribofuranosyl-5H-pyrrolo [3,2-d]pyrimidin-4(3H)-one (12) and the corresponding 6-bromo derivative (13), showed good prophylactic activity in this virus model system.
在傅克反应条件下实现了两种鸟嘌呤类似物9-脱氮鸟嘌呤和7-脱氮鸟嘌呤的C-糖基化反应，分别为9-脱氮鸟苷（4；2-氨基-7-β-D-呋喃核糖基-5H-吡咯并[3,2-d]嘧啶-4(3H)-酮）和8-β-D-呋喃核糖基-7-脱氮鸟嘌呤（16）提供了一条直接的合成路线。这种亲电C-糖基化反应成功应用于六种鸟嘌呤和取代鸟嘌呤类似物，产率约为50%。这是首次报道的与鸟嘌呤等排的预制氮杂环的C-核糖基化反应。相对于用作阳性对照的7-硫代-8-氧代鸟苷，评估了这些C-核苷对小鼠致命性塞姆利基森林病毒感染的防护能力。其中两种C-核苷，2-氨基-6-氯-5-甲基-7-β-D-呋喃核糖基-5H-吡咯并[3,2-d]嘧啶-4(3H)-酮（12）和相应的6-溴衍生物（13），在该病毒模型系统中显示出良好的预防活性。
