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.
Synthesis of Tulipalin A-Based Bispiro[oxazinane-oxindole]Hybrids
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.
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