2-hydroxy-1-(3-methylbut-2-en-1-yl)-9H-carbazole-3-carbaldehyde | 17750-35-5

• 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-hydroxy-1-(3-methylbut-2-en-1-yl)-9H-carbazole-3-carbaldehyde
• 英文别名: heptaphylline；heptahylline；heptaphyline；2-hydroxy-1-(3-methyl-but-2-enyl)-carbazole-3-carbaldehyde；Heptaphyllin；2-hydroxy-1-(3-methylbut-2-enyl)-9H-carbazole-3-carbaldehyde
• CAS: 17750-35-5
• 化学式: C₁₈H₁₇NO₂
• 分子量: 279.338
• InChiKey: ICYHRFZZQCYWNF-UHFFFAOYSA-N

物化性质

• 物理描述：
  Solid
• 熔点：
  171-172°C

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-hydroxy-1-(3-methylbut-2-en-1-yl)-9H-carbazole-3-carbaldehyde 在 甲酸 作用下， 反应 1.0h， 生成 Cycloheptaphyllin
  参考文献：
  名称：

  Structure and synthesis of heptaphylline

  摘要：

  DOI：

  10.1016/s0031-9422(00)90173-0
• 作为产物：
  描述：

  4-bromo-5-iodo-2-methoxybenzaldehyde 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 bis(2,2,6,6-tetramethylpiperidin-1-yl)magnesium-bis(lithium chloride) complex 、 三氯化硼 、 四丁基碘化铵 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 15.75h， 生成 2-hydroxy-1-(3-methylbut-2-en-1-yl)-9H-carbazole-3-carbaldehyde
  参考文献：
  名称：

  Synthesis of Substituted Indoline and Carbazole by Benzyne-Mediated Cyclization–Functionalization

  摘要：

  A benzyne-mediated synthesis of substituted indolines and carbazoles was developed. The reaction includes generation of benzyne using Mg(TMP)(2)center dot 2LiCl as a base, cyclization, and trapping the resulting organomagnesium intermediate with an electrophile to provide a series of substituted indolines and carbazoles in a regiospecific manner. This was applied to a concise five-pot total synthesis of heptaphylline.

  DOI：

  10.1021/ol400597f

文献信息

• Synthesis of Carbazole Alkaloids by Ring‐Closing Metathesis and Ring Rearrangement–Aromatization
  作者：Kalyan Dhara、Tirtha Mandal、Joydeb Das、Jyotirmayee Dash

  DOI：10.1002/anie.201508746

  日期：2015.12.21

  Aprocess for the assembly of carbazole alkaloids has been developed on the basis of ring‐closing metathesis (RCM) and ringrearrangement–aromatization (RRA) as the key steps. This method is based on allyl Grignard addition to isatin derivatives to provide smooth access to 2,2‐diallyl 3‐oxindole derivatives through a 1,2‐allyl shift. The diallyl derivatives were used as RCM precursors to afford a novel

  咔唑生物碱的组装工艺是在关键步骤闭环复分解（RCM）和环重排芳构化（RRA）的基础上开发的。该方法基于烯丙基格利雅（IRAlly Grignard）除以伊斯丁衍生物之外，从而通过1,2-烯丙基转移可平稳地获得2,2-二烯丙基3-氧吲哚衍生物。二烯丙基衍生物用作RCM前体，以提供一类新的螺环戊烯-3-氧吲哚衍生物，该衍生物经过新颖的RRA反应以提供咔唑衍生物。通过在正交串联催化过程中结合RCM和RRA步骤，缩短了咔唑的合成顺序。咔唑生物碱的直接合成进一步证明了这种方法的实用性，其中包括阿莫konal衍生物，girinimbilol，heptaphylline，
• Synthesis of Prenyl- and Geranyl-Substituted Carbazole Alkaloids by DIBAL-H Promoted Reductive Pyran Ring Opening of Dialkylpyrano[3,2-<i>a</i>]carbazoles
  作者：Ronny Hesse、Olga Kataeva、Arndt W. Schmidt、Hans-Joachim Knölker

  DOI：10.1002/chem.201403645

  日期：2014.7.28

  The DIBAL‐H promoted reductive pyran ring opening of dialkylpyrano[3,2‐a]carbazoles provides a direct access to a broad range of prenyl‐ and geranyl‐substituted carbazoles. Formation of a pyran ring followed by reductive ring opening represents a new method for the introduction of prenyl and geranyl groups. In the course of the present work, we achieved the first total syntheses of the following eight

  DIBAL-H促进了二烷基吡喃并[3,2- a ]咔唑的还原吡喃环的打开，可直接使用各种异戊二烯基和香叶基取代的咔唑。吡喃环的形成然后还原性开环代表了引入异戊二烯基和香叶基的新方法。在目前的工作过程中，我们完成了以下八种咔唑生物碱的首次合成：clauraila-E，7-羟基庚茶碱，7-甲氧基庚茶碱，mukoenine-B（clausenatine-A），mukoenine-A（girinimbilol），mahanimbinol （马哈宁比洛），欧司他汀-A和异莫拉利福林-B.
• Semi-Synthesis of Small Molecules of Aminocarbazoles: Tumor Growth Inhibition and Potential Impact on p53
  作者：Solida Long、Joana B. Loureiro、Carla Carvalho、Luís Gales、Lucília Saraiva、Madalena M. M. Pinto、Ploenthip Puthongking、Emília Sousa

  DOI：10.3390/molecules26061637

  日期：——

  their potential effect on wild-type and mutant p53 activity using a yeast screening assay and on human tumor cell lines. Naturally-occurring carbazoles 1–3 showed the most potent growth inhibitory effects on wild-type p53-expressing cells, being heptaphylline (1) the most promising in all the investigated cell lines. However, compound 1 also showed growth inhibition against non-tumor cells. Conversely

  在约50％的人类癌症中，抑癌基因p53通过突变而失活。结合并稳定那些突变体的小分子可能代表有效的抗癌药。在本文中，我们报告了咔唑生物碱和氨基衍生物对肿瘤细胞生长的抑制活性，以及​​它们对p53的潜在激活作用。从七氢茶碱（1），7-甲氧基七氢茶碱（2）和7-甲氧基粘康糖醛（3）分离了十二种氨基咔唑生物碱，而七氯甲碱是从克劳森纳（Clausena harmandiana）分离得到的。，使用还原胺化方案。使用酵母筛选试验和人类肿瘤细胞系评估了天然存在的咔唑1-3及其氨基衍生物对野生型和突变型p53活性的潜在影响。天然存在的咔唑1-3对七型茶碱对野生型p53表达细胞具有最强的生长抑制作用（1）是所有研究过的细胞系中最有前途的。然而，化合物1也显示出针对非肿瘤细胞的生长抑制。相反，半合成的氨基咔唑1d在表达野生型和突变型p53的肿瘤细胞中表现出有趣的生长抑制活性，对非肿瘤细胞的生长抑制作用很低。酵母
• Synthesis, biological evaluation and molecular modeling study of novel tacrine–carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease
  作者：Supatra Thiratmatrakul、Chavi Yenjai、Pornthip Waiwut、Opa Vajragupta、Prasert Reubroycharoen、Michihisa Tohda、Chantana Boonyarat

  DOI：10.1016/j.ejmech.2014.01.020

  日期：2014.3

  New tacrine–carbazole hybrids were developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. The developed compounds showed high inhibitory activity on acetylcholinesterase (AChE) with IC50 values ranging from 0.48 to 1.03 μM and exhibited good inhibition selectivity against AChE over butyrylcholinesterase (BuChE). Molecular

  新型他克林-咔唑杂种被开发为潜在的多功能抗阿尔茨海默病药物，因其具有抑制胆碱酯酶和清除自由基的活性。所开发的化合物对乙酰胆碱酯酶（AChE）具有很高的抑制活性，IC 50值范围从0.48至1.03μM，相对于丁酰胆碱酯酶（BuChE）表现出对AChE的良好抑制选择性。分子模型研究表明，这些他克林-咔唑杂化物与AChE的催化活性位点（CAS）和外围阴离子位点（PAS）同时相互作用。含有甲氧基的衍生物显示出有效的ABTS自由基清除活性。考虑到它们的神经保护作用，我们的结果表明这些衍生物可以减少氧化应激和β-淀粉样蛋白（Aβ）诱导的神经元死亡。此外，S1，具有最大的清除自由基和抑制AChE活性的能力，具有改善东pol碱所致小鼠短期和长期记忆缺陷的能力。全面的，
• Synthesis and cytotoxic activity of the heptaphylline and 7-methoxyheptaphylline series
  作者：Tula Thongthoom、Pawantree Promsuwan、Chavi Yenjai

  DOI：10.1016/j.ejmech.2011.05.041

  日期：2011.9

  Nineteen carbazole alkaloids modified from heptaphylline (I) and 7-methoxyheptaphylline (II) isolated from Clausena harmandiana were synthesized. Among these derivatives, Ih and IIi showed cytotoxicity against the NCI-H187 cell line with IC50 values of 0.02 and 0.66 mu M, respectively, which are about 138 and 4 fold stronger than the ellipticine standard. In addition, oxime Ih displayed cytotoxicity against KB cells with an IC50 value of 0.17 mu M which is about 10 times stronger than the ellipticine. This compound demonstrated weak cytotoxicity against Vero cells (IC50 = 66.01 mu M). The results show convincingly that Ih may be a promising lead for the development of cytotoxic agents. (C) 2011 Elsevier Masson SAS. All rights reserved.