开发一种有效而直接的方法提高螺环氧化吲哚的结构多样性,对于进一步进行生物测试具有重要的研究意义.以靛红、脯氨酸和郁金香素A为起始原料,通过[3 +2]环加成反应,N-氧化反应和分子内 1,2-迁移和扩环反应,得到8 个新型目标产物郁金香素A拼接恶嗪啉双螺环氧化吲哚(4a～4h),总产率为 50%～62%,dr>20 ∶1,产物结构经1 H NMR,13 C NMR和HR-MS(ESI-TOF)表征,化合物4g的相对构型通过单晶X-射线衍射进行了进一步确定.化合物4g属Monoclinic晶系,P21/n空间群.反应机理表明:靛红和脯氨酸先与郁金香素A发生[3 +2]环加成反应,生成环加成中间体 3;中间体 3 中的氮原子在氧化剂间氯过氧苯甲酸的作用下发生N-氧化反应,得到不稳定的中间体3';中间体 3'再发生分子内 1,2-迁移和扩环反应,得到目标产物 4.结果表明:该类新型拼接衍生物4 可为生物活性测试提供新化合物筛选.
Abstract
Developing an effective and direct method to enhance the structural diversity of spiroxindoles is of great research significance for further biological testing.In this paper,we uses isatins,prolines and tulipin A as starting materials,the reaction undergoes a[3 +2]cycloaddition reaction and then N-oxidation reaction,intramolecular 1,2-migration and ring expansion reaction to provide eight tulipalin A-based bispiro[oxazinane-oxindole]hybrids(4a～4h)in 50%～62%overall yields and dr>20 ∶1.The structures of products 4 were characterized by 1 H NMR,13 C NMR and HR-MS(ESI-TOF).The relative configuration of compound 4g was further determined by single crystal X-ray diffraction.And compound 4g belongs to the Monoclinic crystal system,with a P21/n spatial group.The reaction mechanism indicates that isatins and proline first undergo a[3 +2]cycloaddition reaction with tulipin A to form cycloaddition intermediate 3.Then,the nitrogen atom in intermediate 3 undergoes an N-oxi-dation reaction under the action of the oxidant m-chloroperoxybenzoic acid,resulting in an unstable in-termediate 3'.Subsequently,intermediate 3' undergoes intramolecular 1,2-migration and ring expan-sion reaction,resulting in the target product 4.This type of novel hybrid derivatives 4 can provide new compound screening for biological activity testing in the future.
维普
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