2-[2-phenylethenyl]-5-methoxy-1H-indole

• 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-[2-phenylethenyl]-5-methoxy-1H-indole
• 英文别名: 5-methoxy-2-(2-phenylethenyl)-1H-indole
• 化学式: C₁₇H₁₅NO
• 分子量: 249.312
• InChiKey: FMUCFSOJVPMIAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  25
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-[2-phenylethenyl]-5-methoxy-1H-indole 在 manganese(IV) oxide 、 sodium hydride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 42.25h， 生成 9-methoxy-6-methyl-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
  参考文献：
  名称：

  4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution

  摘要：

  High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]carbazole- 1,3(2H,6H)-dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2'-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.

  DOI：

  10.1021/jm0512591

文献信息

• Acid-Relayed Organocatalytic<i>exo</i>-Diels-Alder Cycloaddition of Cyclic Enones with 2-Vinyl-1<i>H</i>-indoles
  作者：Ji-Wei Ren、Zhao-Fang Zhou、Jun-An Xiao、Xiao-Qing Chen、Hua Yang

  DOI：10.1002/ejoc.201501619

  日期：2016.3

  With the aid of the hydrogen-bond relay of (S)-camphorsulfonic acid, the enantioselective exo-Diels–Alder cycloaddition of cyclic enones and 2-vinyl-1H-indoles catalyzed by prolinosulfonamide was developed. The corresponding Diels–Alder cycloadducts were readily obtained by a single recrystallization, free of column chromatography. Consequently, tetracyclic tetrahydrocarbazole ring systems with three

  借助（S）-樟脑磺酸的氢键中继，开发了由脯氨酰磺酰胺催化的环烯酮和2-乙烯基-1H-吲哚的对映选择性exo-Diels-Alder环加成反应。相应的 Diels-Alder 环加合物很容易通过单次重结晶获得，无需柱层析。因此，以中等产率制备了具有三个连续立体中心的四环四氢咔唑环系统，具有优异的非对映选择性（外/内高达 >20:1）和对映选择性（高达 > 99% ee）。
• <i>L</i>-Pyroglutamic Sulphonamide as Hydrogen-Bonding Organocatalyst: Enantioselective Diels–Alder Cyclization to Construct Carbazolespirooxindoles
  作者：Ji-Wei Ren、Jing Wang、Jun-An Xiao、Jun Li、Hao-Yue Xiang、Xiao-Qing Chen、Hua Yang

  DOI：10.1021/acs.joc.7b00733

  日期：2017.6.16

  applied in catalyzing asymmetric Diels–Alder cyclization of methyleneindolinones with 2-vinyl-1H-indoles to efficiently assemble carbazolespirooxindoles in excellent stereoselectivity (up to 99% ee, >20:1 dr) and yields (up to 99%). Mechanistic studies disclosed that the well-designed hydrogen-bonding modes between L-pyroglutamic sulphonamide and substrates were crucial for stereocontrol in the cyclization

  氢键结合的有机催化剂L-焦谷氨酸磺酰胺是通过充分利用L-焦谷氨酸的潜力而容易地首次合成的。新设计的催化剂已成功地用于催化亚甲基吲哚酮与2-乙烯基-1 H-吲哚的不对称Diels-Alder环化反应，从而以优异的立体选择性（高达99％ee，> 20：1 dr）和产率（高达99％）。机理研究表明，L-焦谷氨酸磺酰胺与底物之间设计良好的氢键模式对于环化中的立体控制至关重要。
• A Hypervalent Cyclic Dibenzoiodolium Salt as a Halogen‐Bond‐Donor Catalyst for the [4+2] Cycloaddition of 2‐Alkenylindoles
  作者：Yuki Nishida、Takumi Suzuki、Yuri Takagi、Emi Amma、Ryoya Tajima、Satoru Kuwano、Takayoshi Arai

  DOI：10.1002/cplu.202100089

  日期：2021.5

  A stable, hypervalent cyclic dibenzoiodolium salt acted as a strong halogen bonding (XB)‐donor catalyst for [4+2] cycloaddition of 2‐alkenylindoles, and not as an oxidizing agent. The cross‐[4+2] cycloaddition of 2‐vinylindoles with 2‐alkenylindoles was catalyzed smoothly by the hypervalent cyclic dibenzoiodolium triflate catalyst to give the tetrahydrocarbazoles in up to 99 % yield with 17 : 1 diastereoselectivity

  一种稳定的高价环状二苯并碘鎓盐充当 2-烯基吲哚 [4+2] 环加成的强卤素键 (XB) 供体催化剂，而不是氧化剂。高价环状二苯并碘鎓三氟甲磺酸盐催化剂顺利催化2-乙烯基吲哚与2-烯基吲哚的交叉[4+2]环加成反应，得到四氢咔唑，收率高达99%，非对映选择性为17:1。高价环状二苯并碘鎓盐也适用于 2-乙烯基吲哚与N-对-甲氧基苯基 (PMP) 亚胺的 Povarov 反应，生成吲哚基四氢喹啉，产率 83%。
• Asymmetric Vinylogous Diels-Alder Reactions Catalyzed by a Chiral Phosphoric Acid
  作者：Xu Tian、Nora Hofmann、Paolo Melchiorre

  DOI：10.1002/anie.201310487

  日期：2014.3.10

  to extend the synthetic utility of the Diels–Alder reaction to include a vinylogous reactivity space is described. A commercially available chiral phosphoric acid catalyst effectively activates cyclic 2,4‐dienones towards a vinylogous [4+2] cycloaddition with 2‐vinylindoles, which leads to stereochemically dense tetrahydrocarbazoles. The reaction proceeds with a high level of remote stereocontrol and

  描述了一种前所未有的方式来扩展Diels-Alder反应的合成效用，使其包括乙烯基反应空间。市售的手性磷酸催化剂可有效地将环状2,4-二烯酮激活，与2-乙烯基吲哚类化合物发生乙烯基[4 + 2]环加成反应，从而形成立体化学稠密的四氢咔唑。该反应以较高水平的远程立体控制和对二烯酮更远的双键的排他性化学选择性进行。
• Synthesis and structure–activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpoint kinases
  作者：Jeff B. Smaill、Edward N. Baker、R. John Booth、Alexander J. Bridges、James M. Dickson、Ellen M. Dobrusin、Ivan Ivanovic、Alan J. Kraker、Ho H. Lee、Elizabeth A. Lunney、Daniel F. Ortwine、Brian D. Palmer、John Quin、Christopher J. Squire、Andrew M. Thompson、William A. Denny

  DOI：10.1016/j.ejmech.2007.07.016

  日期：2008.6

  A series of N-6 substituted 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones were prepared from N-substituted (5-methoxyphenyl)ethenylindoles. The target compounds were tested for their ability to inhibit the G2/M cell cycle checkpoint kinases, Wee1 and Chk1. Analogues with neutral or cationic N-6 side chains were potent dual inhibitors. Acidic side chains provided potent (average IC(50) 0.057 microM) and selective (average ratio 223-fold) Wee1 inhibition. Co-crystal structures of inhibitors bound to Wee1 show that the pyrrolo[3,4-c]carbazole scaffold binds in the ATP-binding site, with N-6 substituents involved in H-bonding to conserved water molecules. HT-29 cells treated with doxorubicin and then target compounds demonstrate an active Cdc2/cyclin B complex, inhibition of the doxorubicin-induced phosphorylation of tyrosine 15 of Cdc2 and abrogation of the G2 checkpoint.