2-(6-chloro-2-methyl-1H-indol-3-yl)ethanol | 872675-03-1

• 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-(6-chloro-2-methyl-1H-indol-3-yl)ethanol
• CAS: 872675-03-1
• 化学式: C₁₁H₁₂ClNO
• 分子量: 209.675
• InChiKey: ORORYSXGBOITJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  36
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(6-chloro-2-methyl-1H-indol-3-yl)ethanol 在 偶氮二甲酸二异丙酯 、 sodium hydride 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 methyl 4-[2-[6-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]ethoxy]benzoate
  参考文献：
  名称：

  Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization

  摘要：

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.

  DOI：

  10.1021/jm0507882
• 作为产物：
  描述：

  Aceton-(m-chlor-phenylhydrazon) 在 lithium aluminium tetrahydride 、 三乙胺 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 1.0h， 生成 2-(6-chloro-2-methyl-1H-indol-3-yl)ethanol
  参考文献：
  名称：

  Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization

  摘要：

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.

  DOI：

  10.1021/jm0507882

文献信息

• Oxidative Indole Dearomatization for Asymmetric Furoindoline Synthesis by a Flavin‐Dependent Monooxygenase Involved in the Biosynthesis of Bicyclic Thiopeptide Thiostrepton
  作者：Zhi Lin、Yufeng Xue、Xiao‐Wei Liang、Jian Wang、Shuangjun Lin、Jiang Tao、Shu‐Li You、Wen Liu

  DOI：10.1002/anie.202013174

  日期：2021.4.6

  subsequent epoxide opening in a highly enantioselective manner during the conversion of 2‐methyl‐indole‐3‐acetic acid or 2‐methyl‐tryptophol to furoindoline, with up to >99 % conversion and >99 % ee under mild reaction conditions. Complementing current chemical methods for oxidative indole dearomatization, the TsrE activity‐based approach enriches the toolbox in the asymmetric synthesis of products

  近年来，人们对吲哚脱芳香化的兴趣不断提高，这种兴趣在相关生物碱天然产物的全合成中是一种有用的工具，目的是开发在产量和立体选择性控制方面均有效的新方法。在这里，我们报告了一种酶促方法，用于在邻位季铵碳立体异构中心的各种呋喃二氢吲哚的不对称合成中对吲哚进行氧化脱芳香化作用。这种方法取决于黄素依赖性单加氧酶TsrE的活性，该酶参与双环硫肽抗生素硫链丝菌素的生物合成。在2-甲基-吲哚-3-乙酸或2-甲基-色酚转化为呋喃二氢的过程中，TsrE以高对映选择性的方式催化2,3-环氧化和随后的环氧化物开环，转化率> 99％，> 99％ee在温和的反应条件下。TsrE活性为基础的方法补充了当前的氧化吲哚脱芳香化的化学方法，丰富了具有呋喃二氢骨架的产品的不对称合成中的工具箱。
• Asymmetric Fluorinative Dearomatization of Tryptophol Derivatives by Chiral Anion Phase-Transfer Catalysis
  作者：Xiao-Wei Liang、Yue Cai、Shu-Li You

  DOI：10.1002/cjoc.201800319

  日期：2018.10

  An asymmetric fluorinative dearomatization reaction of tryptophol derivatives was developed via chiral anion phase‐transfer catalysis. Various fluorinated furoindolines were obtained in moderate to excellent yields and enantioselectivity in the presence of Selectfluor. The preliminary mechanistic studies suggested the existence of an in situ formed tryptophol boronic ester plays a critical role in

  通过手性阴离子相转移催化开发了三氯酚衍生物的不对称氟化脱芳香化反应。在存在Selectfluor的情况下，以中等至极好的收率和对映选择性获得了各种氟化呋喃二氢。初步的力学研究表明，原位形成的胰多酚硼酸酯的存在在确定对映选择性方面起着至关重要的作用。该方法的特点是易于以高度对映选择性的方式引入氟原子，并构建了两个连续的四级立体异构中心。
• Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization
  作者：John C. McKew、Megan A. Foley、Paresh Thakker、Mark L. Behnke、Frank E. Lovering、Fuk-Wah Sum、Steve Tam、Kun Wu、Marina W. H. Shen、Wen Zhang、Mario Gonzalez、Shanghao Liu、Anu Mahadevan、Howard Sard、Soo Peang Khor、James D. Clark

  DOI：10.1021/jm0507882

  日期：2006.1.1

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.