García Martínez A, Teso Vilar E, García Fraile A, de la Moya Cerero S, Rodríguez Herrero M E, Martínez Ruiz P, Subramanian L R, García Gancedo A
Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Complutense, Madrid, Spain.
J Med Chem. 1995 Oct 27;38(22):4474-7. doi: 10.1021/jm00022a012.
The reaction of (+/-)-camphor (7) with triflic anhydride (Tf2O) yields the bridgehead triflate 8. The Nametkin rearrangement of 8 to 3 was realized by treatment with triflic acid (TfOH). The solvolysis of the bridgehead triflates 3 and 8 in acetonitrile affords the N-acetyl-1-norbornylamines 4 and 9. The Pd(0)-catalyzed hydrogenation of 4 and 9 gives the amides 5 and 10. The corresponding 1-norbornylamines 2 and 13 and the N-ethyl derivatives 1, 6, 11, and 12 were obtained by basic hydrolysis or reduction with LiAlH4, respectively, of the amides 4, 5, 9, and 10. The antiviral activity of the hydrochlorides of some of the obtained 1-norbornylamines was evaluated against influenza A, herpes simplex 2, and African swine fever virus. Particularly noticeable is the activity of the hydrochlorides of 1 and 11 against influenza A virus (SI (selectivity index) = 1000).
（±）-樟脑（7）与三氟甲磺酸酐（Tf2O）反应生成桥头三氟甲磺酸酯8。通过用三氟甲磺酸（TfOH）处理，将8进行Nametkin重排得到3。桥头三氟甲磺酸酯3和8在乙腈中的溶剂解反应得到N-乙酰基-1-降冰片胺4和9。4和9的钯（0）催化氢化反应得到酰胺5和10。分别通过酰胺4、5、9和10的碱性水解或用LiAlH4还原，得到相应的1-降冰片胺2和13以及N-乙基衍生物1、6、11和12。对所得到的一些1-降冰片胺的盐酸盐针对甲型流感病毒、单纯疱疹病毒2和非洲猪瘟病毒的抗病毒活性进行了评估。特别值得注意的是1和11的盐酸盐对甲型流感病毒的活性（选择性指数（SI）=1000）。
