methyl 5,7-dimethoxy-1,3-dimethylindole-2-carboxylate | 219325-82-3

• 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: methyl 5,7-dimethoxy-1,3-dimethylindole-2-carboxylate
• CAS: 219325-82-3
• 化学式: C₁₄H₁₇NO₄
• 分子量: 263.293
• InChiKey: QXLJSBCHVXEQQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 5,7-dimethoxy-1,3-dimethylindole-2-carboxylate 在 ammonium cerium(IV) nitrate 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以21%的产率得到5-Methoxy-1,3-dimethyl-4,7-dioxo-4,7-dihydro-1H-indole-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Indolequinone Antitumor Agents:  Correlation between Quinone Structure, Rate of Metabolism by Recombinant Human NAD(P)H:Quinone Oxidoreductase, and in Vitro Cytotoxicity

  摘要：

  A series of indolequinones bearing various functional groups has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H: quinone oxidoreductase (NQO1) were studied. Thus 5-methoxyindolequinones were prepared by the Nenitzescu reaction, followed by functional group interconversions. The methoxy group was subsequently displaced by amine nucleophiles to give a series of amine-substituted quinones. Metabolism of the quinones by NQO1 revealed that, in general, compounds with electron-withdrawing groups at the indole 3-position were among the best substrates, whereas those with amine groups at the 5-position were poor substrates. Compounds with a leaving group at the 3-indolyl methyl position generally inactivated the enzyme. The toxicity toward non-small-cell lung cancer cells with either high NQO1 activity (H460) or no detectable activity (H596) was also studied in representative quinones. Compounds which were good substrates for NQO1 showed the highest selectivity between the two cell lines.

  DOI：

  10.1021/jm980328r
• 作为产物：
  描述：

  2-Diazo-3-oxo-butyric acid methyl ester 在 dirhodium tetraacetate Amberlyst 15 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成 methyl 5,7-dimethoxy-1,3-dimethylindole-2-carboxylate
  参考文献：
  名称：

  N-H Insertion Reactions of Rhodium Carbenoids: A Modified Bischler Indole Synthesis

  摘要：

  在醋酸铑（II）催化下，δ-偶氮δ-酮ters 与 N-甲基苯胺发生反应，导致类羰基插入 N-H 键；生成的δ-（N-芳基氨基）酮在酸性离子交换树脂的处理下环化生成吲哚。

  DOI：

  10.1055/s-1998-1610

文献信息

• N-H Insertion Reactions of Rhodium Carbenoids: A Modified Bischler Indole Synthesis
  作者：Christopher J. Moody、Elizabeth Swann

  DOI：10.1055/s-1998-1610

  日期：1998.2

  Rhodium(II) acetate catalysed reaction of α-diazo-β-ketoesters with N-methylanilines results in carbenoid insertion into the N-H bond; the resulting α-(N-arylamino)ketones cyclise to give indoles upon treatment with acidic ion-exchange resin.

  在醋酸铑（II）催化下，δ-偶氮δ-酮ters 与 N-甲基苯胺发生反应，导致类羰基插入 N-H 键；生成的δ-（N-芳基氨基）酮在酸性离子交换树脂的处理下环化生成吲哚。
• Indolequinone Antitumor Agents:  Correlation between Quinone Structure, Rate of Metabolism by Recombinant Human NAD(P)H:Quinone Oxidoreductase, and in Vitro Cytotoxicity
  作者：Howard D. Beall、Shannon Winski、Elizabeth Swann、Anna R. Hudnott、Ann S. Cotterill、Noeleen O'Sullivan、Stephen J. Green、Richard Bien、David Siegel、David Ross、Christopher J. Moody

  DOI：10.1021/jm980328r

  日期：1998.11.1

  A series of indolequinones bearing various functional groups has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H: quinone oxidoreductase (NQO1) were studied. Thus 5-methoxyindolequinones were prepared by the Nenitzescu reaction, followed by functional group interconversions. The methoxy group was subsequently displaced by amine nucleophiles to give a series of amine-substituted quinones. Metabolism of the quinones by NQO1 revealed that, in general, compounds with electron-withdrawing groups at the indole 3-position were among the best substrates, whereas those with amine groups at the 5-position were poor substrates. Compounds with a leaving group at the 3-indolyl methyl position generally inactivated the enzyme. The toxicity toward non-small-cell lung cancer cells with either high NQO1 activity (H460) or no detectable activity (H596) was also studied in representative quinones. Compounds which were good substrates for NQO1 showed the highest selectivity between the two cell lines.
• N–H Insertion reactions of rhodium carbenoids. Part 3.1 The development of a modified Bischler indole synthesis and a new protecting-group strategy for indoles
  作者：Katherine E. Bashford、Anthony L. Cooper、Peter D. Kane、Christopher J. Moody、Sendogagounder Muthusamy、Elizabeth Swann

  DOI：10.1039/b202666j

  日期：2002.7.11

  A modified version of the Bischler indole synthesis has been developed in which the key step is the N–H insertion reaction of rhodium carbene intermediates derived from α-diazo-β-ketoesters with anilines. Thus N-methylanilines 1 react with diazoketoesters 2 in the presence of dirhodium(II) acetate to give (N-arylamino)ketones 3, cyclisation of which using boron trifluoride–ethyl acetate or acidic ion exchange resin gives the indoles 4. In order to extend this method to the synthesis of N-unsubstituted indoles, a new protecting group strategy for indoles was developed. In this, anilines are reacted with α,β-unsaturated-esters or -sulfones to give the conjugate addition products 6 and 9, cyclisation of which gives indoles 8 and 11. The N-(2-ethoxycarbonylethyl)- and -(2-sulfonylethyl)- protecting groups are readily removed from indoles 8 and 11 by treatment with base.

  一种改进的Bischler吲哚合成方法已被开发，其中关键步骤是铑卡宾中间体从α-重氮-β-酮酯与苯胺的N-H插入反应。因此，N-甲基苯胺1与重氮酮酯2在二铑(II)醋酸盐存在下反应生成(N-芳氨基)酮3，使用三氟化硼-乙酸乙酯或酸性离子交换树脂进行环化反应得到吲哚4。为了将这种方法扩展到N-未取代的吲哚的合成，开发了一种新的吲哚保护基团策略。在此过程中，苯胺与α,β-不饱和酯或砜反应生成共轭加成产物6和9，其环化反应生成吲哚8和11。N-(2-乙氧羰基乙基)- 和 -(2-砜乙基)- 保护基团通过用碱处理从吲哚8和11中容易地去除。