Inamoto Y, Aigami K, Takaishi N, Fujikura Y, Ohsugi M, Ikeda H, Tsuchihashi K, Takatsuki A, Tamura G
J Med Chem. 1979 Oct;22(10):1206-14. doi: 10.1021/jm00196a011.
Functionalization reactions via cationic intermediates of tricyclo[4.3.1.1 2,5]undecane (2) were investigated to prepare derivatives with potential antiviral activities. Bromination of 2 took place regiospecifically at C-1, and the resulted bromide 5 was converted into the hydroxide 9, the carboxylic acid 12, and the amine 22, from which were synthesized a variety of secondary derivatives, including homologous esters 10 and 20, amides 14 and 19, carbamates 24, and ureas 17 and 25. The hydroxide 9, the acid 12, and the acetamide 21 were also obtainable directly from tricyclo[5.2.1.0 2,6]dec-endo-2-ylcarbinol (1), the precursor for the synthesis of the hydrocarbon 2. Success in these functionalization-rearrangements was attributed to the inability of the intermediate 2-1-yl cation (2+) for further skeletal isomerizations. Among the 1-substituted derivatives of 2 prepared, the amine hydrochlorides (16 and 23), a few esters (20b and 20d), and some N-alkylamides (19c, 19d, and 19e) exhibited marked antiviral activities as compared to amantadine hydrochloride, when tested in vitro on a monolayer culture of chick embryo fibroblasts against Newcastle disease virus.
研究了通过三环[4.3.1.12,5]十一烷（2）的阳离子中间体进行的官能化反应，以制备具有潜在抗病毒活性的衍生物。2在C-1位发生区域特异性溴化反应，生成的溴化物5被转化为氢氧化物9、羧酸12和胺22，由此合成了多种二级衍生物，包括同系酯10和20、酰胺14和19、氨基甲酸酯24以及脲17和25。氢氧化物9、酸12和乙酰胺21也可直接由三环[5.2.1.02,6]癸-endo-2-基甲醇（1）制得，1是合成烃2的前体。这些官能化重排反应的成功归因于中间体2-1-基阳离子（2+）无法进一步进行骨架异构化。在制备的2的1-取代衍生物中，与盐酸金刚烷胺相比，胺盐酸盐（16和23）、一些酯（20b和20d）以及一些N-烷基酰胺（19c、19d和19e）在体外针对鸡胚成纤维细胞单层培养物对抗新城疫病毒的测试中表现出显著的抗病毒活性。
