郁金香素A拼接双螺环恶嗪啉-氧化吲哚的合成  

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

作　　者：任娜 石庆辉 王慧娟[1] 姜维艳 刘雄利[1] 邓国栋[1] REN Na;SHI Qinghui;WANG Huijuan;JIANG Weiyan;LIU Xiongli;DENG Guodong(National&Local Joint Engineering Research Center for The Exploition of Homology Resources of Medicineand Food,Guizhou University,Guiyang 550025,China;Guizhou Equipmet Manufacturing Vocational College,Guiyang 550025,China)

机构地区：[1]贵州大学西南药食两用资源开发利用技术国家地方联合工程研究中心,贵州贵阳550025 [2]贵州装备制造职业学院,贵州贵阳550025

出　　处：《合成化学》2024年第2期101-107,共7页Chinese Journal of Synthetic Chemistry

基　　金：药用桑属植物中异戊烯基黄酮类物质基础及其抗骨质疏松活性研究项目(贵大培育[2020]52号)。

摘　　要：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,P 21/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。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 P 21/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-oxidation reaction under the action of the oxidant m-chloroperoxybenzoic acid,resulting in an unstable intermediate 3′.Subsequently,intermediate 3′undergoes intramolecular 1,2-migration and ring expansion 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.

关 键 词：郁金香素A 恶嗪啉 螺环氧化吲哚 [3+2]环加成反应 N-氧化反应 

分 类 号：O626.13[理学—有机化学] O623.7[理学—化学]