申请人:DUPHAR INTERNATIONAL RESEARCH B.V
公开号:EP0401929A2
公开(公告)日:1990-12-12
The invention relates to a method of preparing N-oxo-tetrahydro-β-carbolines having formula 1.
wherein
- R₁ is lower alkyl or alkoxy, halogen, trifluoromethyl, lower alkylthio, hydroxy, amino, lower mono- or dialkyl- or acylamino,
- n has the value 0, 1 or 2,
- R₂ is hydrogen, lower alkyl or acyl,
- R₃ is hydrogen, lower alkyl or alkoxycarbonyl, or a phenyl group optionally substituted with a group R₁, and
- A together with the group -C-N-O-, forms a saturated heterocyclic ring system consisting of 6-8 ring atoms, wherein, in addition to the already present oxygen atom and nitrogen atom, an extra hetero atom from the group O, S and N may be present, which ring system may be substituted with one or more of the substituents alkyl,alkoxycarbonyl, alkanoyl, alkoxy, hydroxy, oxo, amino, mono- or dialkylamino, alkanoyl- or alkoxycarbonylamino, which ring system may be annelated with a saturated carbocyclic group of 5 or 6 ring atoms, by an intramolecular ringclosure reaction of compounds of formula 2
wherein Z is an aldehyde function or acetal function, or is a functional group which can be converted into such a function during the ringclosure reaction.
The eudistomin derivatives within the group of compounds having formula 1 have strong antiviral and antitumour activity.
本发明涉及一种制备具有式 1 的 N-氧代四氢-β-羰基化合物的方法。
其中
- R₁ 是低级烷基或烷氧基、卤素、三氟甲基、低级烷硫基、羟基、氨基、低级单烷基或二烷基或酰氨基、
- n 的值为 0、1 或 2、
- R₂ 是氢、低级烷基或酰基、
- R₃ 是氢、低级烷基或烷氧基羰基,或任选被基团 R₁ 取代的苯基,以及
- A 与基团-C-N-O-一起,形成一个由 6-8 个环原子组成的饱和杂环系统,其中,除了已经存在的氧原子和氮原子外,还可能存在一个来自 O、S 和 N 组的额外杂原子,该环系可被一个或多个取代基烷基取代、烷氧基羰基、烷酰基、烷氧基、羟基、氧代、氨基、单烷基或二烷基氨基、烷酰基或 烷氧基羰基氨基,通过式 2 化合物的分子内封环反应,该环系可与 5 或 6 个环原子的饱和碳环基团环化
其中 Z 是醛官能团或缩醛官能团,或者是可在封环反应中转化为此类官能团的官能团。
式 1 化合物组中的桉叶烷衍生物具有很强的抗病毒和抗肿瘤活性。