2-(1-Benzyl-5-methoxy-2-oxoindol-3-ylidene)propanedinitrile | 862116-09-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-(1-Benzyl-5-methoxy-2-oxoindol-3-ylidene)propanedinitrile
• CAS: 862116-09-4
• 化学式: C₁₉H₁₃N₃O₂
• 分子量: 315.331
• InChiKey: JFQJUGYJCPOUCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  77.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1-Benzyl-5-methoxy-2-oxoindol-3-ylidene)propanedinitrile 、 白杨素 以 甲醇 为溶剂， 反应 8.0h， 生成 2′-amino-1-benzyl-5′-hydroxy-5-methoxy-2,6′-dioxo-8′-phenyl-6′H-spiro[indoline-3,4′- pyrano[3,2-g]chromene]-3′‑carbonitrile
  参考文献：
  名称：

  Design, synthesis and evaluation of structurally diverse chrysin-chromene-spirooxindole hybrids as anticancer agents

  摘要：

  A series of structurally diverse chrysin-chromene-spirooxindole hybrids were designed, synthesized via a Knoevenagel/Michael/cyclization of chrysin and isatylidene malononitrile derivatives through utilizing a hybrid pharmacophore approach. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds showed stronger anti-proliferative activity than parent compound chrysin. In particular, compound 3e had the highest cytotoxicity towards A549 cells (IC50 = 3.15 +/- 0.51 mu M), and had better selectivity in A549 cells and normal MRC-5 cells. Furthermore, compound 3e could significantly inhibit the proliferation and migration of A549 cells in a dose-dependent manner, as well as induce the apoptosis possibly through mitochondria-mediated caspase-3/8/9 activation and multi-target co-regulation of the p53 signaling pathway. Thus, our results provide in vitro evidence that compound 3e may be a potential candidate for the development of new anti-tumour drugs.

  DOI：

  10.1016/j.bmc.2019.115109
• 作为产物：
  描述：

  5-甲氧基靛红 在 哌啶 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.75h， 生成 2-(1-Benzyl-5-methoxy-2-oxoindol-3-ylidene)propanedinitrile
  参考文献：
  名称：

  以迈克尔（Triple Michael）/环化级联序列为关键步骤的多组分反应构建螺环氧化吲哚

  摘要：

  公开了具有容易获得的异氰酸酯，脲基酸酯和异亚丙基丙二腈的多组分环加成物。该反应不需要任何催化剂的帮助，使得能够以优异的区域选择性有效地合成螺环恶吲哚。还充分探讨了与2,3-丁二烯酸乙酯和各种结构不同的α-和γ-取代的烯醇酸酯的反应。值得注意的是，我们已经表明，通常的三组分过程可以在存在水的情况下进一步发展为史无前例的四组分环加成反应，这提供了一种新的策略来获得高度不寻常的三环羟吲哚。从综合的角度来看，考虑到一步就可以达到很高的复杂性，该协议非常有趣。该机理被认为是通过使用烯丙酸酯作为三个碳原子组分（3 C）通过三重迈克尔/环化过程进行的。此外，与γ-取代的脲基甲酸酯的多组分反应也导致非常有趣的转化。在这种情况下，总是观察到异亚丙基丙二腈的“CC”双键和脲基酸酯的“CC”双键之一的不寻常断裂。

  DOI：

  10.1002/chem.201104071

文献信息

• Triphenylphosphine-Catalyzed [3+2] Cycloaddition of Allenoate and Active Olefins: Syntheses of Spirooxindole Derivatives
  作者：Xueshun Jia、Shanyan Guo、Rendong Wang、Jian Li、Chunju Li、Hongmei Deng

  DOI：10.1055/s-0030-1261188

  日期：2011.9

  A series of spiro compounds was achieved by triphenylphosphine-catalyzed [3+2] cycloaddition between active methylenemalononitrile and ethyl 2,3-butadienoate. Careful investigation showed that the present method had high regioselectivity. The products have a spirooxindole skeleton, which is a motif common in many natural products and pharmaceutically active compounds.

  通过三苯基膦催化的[3+2]环加成反应，成功合成了一系列螺旋化合物，反应物为活性亚甲基马隆腈和乙基2,3-丁二烯酸酯。细致的研究表明，该方法具有较高的区域选择性。产物呈现出螺氧吲哚骨架，这是一种在许多自然产物和药效活性化合物中常见的结构特征。
• Grinding assisted, column chromatography free decarboxylative carbon-carbon bond formation: Greener synthesis of 3, 3-disubstituted oxindoles
  作者：Jasneet Kaur、Anita Kumari、Swapandeep Singh Chimni

  DOI：10.1016/j.tet.2016.12.070

  日期：2017.2

  The decarboxylative carbon-carbon bond formation reaction of β-ketoacid derivatives with isatylidene malononitrile derivatives catalyzed by DBU afford adducts in excellent yield. The desired product can be easily isolated using simple filtration method without performing any column chromatography. The decarboxylative adduct was further subjected to reductive-cyclization to obtain biologically important

  DBU催化β-酮酸衍生物与异亚丙基丙二腈衍生物的脱羧碳-碳键形成反应，得到的加合物收率高。所需产物可以使用简单的过滤方法容易地分离，而无需进行任何柱色谱法。脱羧加合物进一步进行还原环化，以89％的产率获得生物学上重要的螺硫醇。
• Asymmetric synthesis of spirooxindole–pyranoindole products <i>via</i> Friedel–Crafts alkylation/cyclization of the indole carbocyclic ring
  作者：Yuan Gao、Xiaonan Wang、Zhonglin Wei、Jungang Cao、Dapeng Liang、Yingjie Lin、Haifeng Duan

  DOI：10.1039/d0nj00074d

  日期：——

  An efficient enantioselective Friedel–Crafts alkylation/cyclization tandem reaction of the indole carbocyclic ring with isatylidene malononitriles has been performed successfully by using a new bifunctional tertiary amine-urea catalyst. A series of chiral spirooxindole–pyranoindole products were obtained in excellent yields (up to 98% yield) with moderate to good enantioselectivities (up to 85% ee)

  通过使用新型双功能叔胺-脲催化剂，已成功进行了吲哚碳环与异亚丙基丙二腈的高效对映选择性Friedel-Crafts烷基化/环化串联反应。以优异的收率（最高98％的收率）和中等至良好的对映选择性（最高85％ee）获得了一系列手性螺氧基吲哚-吡喃并吲哚产品。
• Iron‐catalyzed one‐pot oxidation/Knoevenagel condensation reaction using air as an oxidant
  作者：Lu‐Shan Huang、Yi‐Huan Lai、Cheng Yang、Da‐Zhen Xu

  DOI：10.1002/aoc.4910

  日期：2019.6

  A green and highly efficient iron‐catalyzed one‐pot oxidation/Knoevenagel tandem reaction for the synthesis of α, β‐unsaturated nitriles from secondary alcohols and malononitrile has been achieved. The reaction performed under mild conditions with air as an oxidant, and provided the corresponding oxidation/Knoevenagel prudocts in good to excellent yields within short times avoiding the use of noble

  实现了绿色高效的铁催化单锅氧化/ Knoevenagel串联反应，可从仲醇和丙二腈合成α，β-不饱和腈。该反应在温和的条件下用空气作为氧化剂进行，避免了使用贵金属催化剂和碱，在短时间内以良好至极好的收率提供了相应的氧化/ Knoevenagel原料。值得注意的是，水是这种方法中唯一的副产物。该反应可以在标准反应条件下以克为单位进行。
• A DBU-catalyzed Michael–Pinner–isomerization cascade reaction of 3-hydroxyoxindoles with isatylidene malononitriles: access to highly functionalized bispirooxindoles containing a fully substituted dihydrofuran motif
  作者：Yan-Shuo Zhu、Wen-Bo Wang、Bei-Bei Yuan、Ya-Ning Li、Qi-Lin Wang、Zhan-Wei Bu

  DOI：10.1039/c6ob02254e

  日期：——

  DBU-catalyzed Michael/Pinner/isomerization cascade reaction of 3-hydrooxindoles with isatylidene malononitriles was developed, and the corresponding highly functionalized bispirooxindoles containing a fully substituted dihydrofuran motif were obtained in up to 92% yields. This protocol also provides an efficient method for the synthesis of an α-cyano-γ-butyrolactone bispirooxindole. In addition, a one-pot three-component

  开发了第一个DBU催化的3-氢氧吲哚与异亚丙基丙二腈的Michael / Pinner /异构化级联反应，并以高达92％的收率获得了相应的含有完全取代的二氢呋喃基序的高度官能化的bispirooxindoles。该方案还提供了一种合成α-氰基-γ-丁内酯双螺并恶唑的有效方法。另外，进行了一锅三组分级联反应。同样，获得了级联反应的不对称形式。