Neurosteroid analogues. 7. A synthetic route for the conversion of 5 beta-methyl-3-ketosteroids into 7(S)-methyl-substituted analogues of neuroactive benz[e]indenes.
Neurosteroid analogues. 7. A synthetic route for the conversion of 5 beta-methyl-3-ketosteroids into 7(S)-methyl-substituted analogues of neuroactive benz[e]indenes.
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神经类固醇类似物。
DOI：
10.1021/jo991953m
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Covey,DF
中科院分区：
文献类型：
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作者：
Zeng,C;Han,M;Covey,DF
我们之前报道过benz [e] indenes 1和2增强了抑制性神经递质γ-氨基丁酸（GABA）对GABAA受体的作用。由于这种药理作用，这些化合物作为鉴定具有抗惊厥、镇静催眠和麻醉活性的新候选药物的先导化合物很有兴趣。从概念上讲，化合物1和2可以通过打破C-2和C-3之间的a环，然后去除C-1和C-2从19-去甾体中得到。事实上，我们已经通过这种途径（臭氧分解Δ2-enol衍生物，然后去除C-1和C-2）从(5R, 17)-17-羟基乙酰酯-3- 1制备了苯并[e]茚1。由于3-酮基团的烯醇化倾向于向C-4方向，因此用这种方法不能从(5,17)-17-羟基甾烷-3- 1类似地制备3,8苯并[e]茚二酮。相反，该化合物是通过全合成制备的。然而，这条路线不是最优的，因为
We previously reported that benz [e] indenes 1 and 2 enhance the actions of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at GABAA receptors. 1-7 Because of this pharmacological action, the compounds are of interest as lead compounds for identifying new drug candidates with anticonvulsant, sedative-hypnotic, and anesthetic activities. Conceptually, compounds 1 and 2 are accessible from 19-norsteroids by breaking the A-ring between C-2 and C-3 and then removing C-1 and C-2. Indeed, we have prepared benz [e] indene 1 from (5R, 17)-17-hydroxyestran-3-one by this route (ozonolysis of a Δ2-enol derivative followed by removal of C-1 and C-2). 3, 8Benz [e] indene 2 could not be similarly prepared from (5, 17)-17-hydroxyestran-3-one by this method because the preferred direction of enolization of the 3-keto group is toward C-4. 9 Instead, this compound was prepared by total synthesis. 4 However, this route is not optimal since