2-methoxy-3,10-dimethylpyrido[1,2-a]indole-1,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 2-methoxy-3,10-dimethylpyrido[1,2-a]indole-1,4-dione
• 化学式: C₁₅H₁₃NO₃
• 分子量: 255.273
• InChiKey: BHCLANCXFNIQTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  47.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-(hydroxymethyl)-6-methoxy-4,7-dimethyl-2,3-dihydro-1H-pyrrolo[1,2-a]indole-5,8-dione 在 palladium on activated charcoal 吡啶 、 air 、 氢气 作用下， 以 甲醇 为溶剂， 反应 29.41h， 生成 2-methoxy-3,10-dimethylpyrido[1,2-a]indole-1,4-dione
  参考文献：
  名称：

  Design of a Cyclopropyl Quinone Methide Reductive Alkylating Agent

  摘要：

  Described herein is the formation of a cyclopropyl quinone methide species by leaving group elimination from an indole-based hydroquinone. This species is structurally related to the A-ring of CC-1065 and is a nucleophile trap. In addition, the cyclopropyl quinone methide species can trap or eliminate a proton. Unlike the A-ring of CC-1065, stereoelectronic factors favor opening of the fused cyclopropane ring so as to result in ring expansion. Also described herein is the utility of C-13 NMR spectroscopy in following the fate of the cyclopropyl quinone methide species. Finally, the cyclopropyl quinone methide species reversibly alkylates the guanine N(7) position of DNA, resulting in cytotoxicity.

  DOI：

  10.1021/jo971808d

文献信息

• Chemistry of Pyrrolo[1,2-<i>a</i>]indole- and Pyrido[1,2-<i>a</i>]indole-Based Quinone Methides. Mechanistic Explanations for Differences in Cytostatic/Cytotoxic Properties
  作者：Omar Khdour、Edward B. Skibo

  DOI：10.1021/jo070866o

  日期：2007.11.1

  pyrrolo[1,2-a]indole-based quinones capable of forming quinone methide and vinyl quinone species upon reduction and leaving group elimination. Our goals were to determine the influence of the 6-membered pyrido and the 5-membered pyrrolo fused rings on quinone methide and vinyl quinone formation and fate as well as on cytostatic and cytotoxic activity. We used the technique of Spectral Global Fitting to study

  在本研究中，我们研究了基于吡啶并[1,2- a ]吲哚和吡咯并[1,2 - a ]吲哚的醌类，它们在还原后可形成醌甲基化物和乙烯基醌，从而消除基团。我们的目标是确定6元吡啶基和5元吡咯并稠环对醌甲基化物和乙烯基醌的形成和命运以及对细胞抑制和细胞毒活性的影响。我们使用“光谱全局拟合”技术直接研究了短暂的甲基苯醌中间体。关于甲基苯醌反应性的结论是，亲核试剂需要羰基O质子化，并且p K a该质子化物种的价值接近中性。异常高的质子化羰基p K a值是由于质子化时形成芳族碳阳离子物质所致。与稠合的吡咯环相比，稠合的吡啶基环促进了甲基醌和乙烯基醌的形成，但减慢了亲核试剂的捕获。这些发现是由于稠合的吡啶基环中存在轴向氢原子导致的，与相对平坦的稠合的吡咯洛环相比，其导致更多的空间拥堵。因此，基于吡咯并[1,2 - a ]吲哚的醌由于其更大的亲核试剂捕获能力而比吡啶并[1,2- a ]吲哚类似物表现出更多的细胞抑制活性。
• Design of a Cyclopropyl Quinone Methide Reductive Alkylating Agent
  作者：Anlong Ouyang、Edward B. Skibo

  DOI：10.1021/jo971808d

  日期：1998.3.1

  Described herein is the formation of a cyclopropyl quinone methide species by leaving group elimination from an indole-based hydroquinone. This species is structurally related to the A-ring of CC-1065 and is a nucleophile trap. In addition, the cyclopropyl quinone methide species can trap or eliminate a proton. Unlike the A-ring of CC-1065, stereoelectronic factors favor opening of the fused cyclopropane ring so as to result in ring expansion. Also described herein is the utility of C-13 NMR spectroscopy in following the fate of the cyclopropyl quinone methide species. Finally, the cyclopropyl quinone methide species reversibly alkylates the guanine N(7) position of DNA, resulting in cytotoxicity.