3,11-二氢-8,9-二甲氧基-3,3,5-三甲基吡喃并[3,2-A]咔唑 | 24123-92-0

• 物质功能分类: 分析化学 - 标准品 - 分析标准品
• 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
• 中文名称: 3,11-二氢-8,9-二甲氧基-3,3,5-三甲基吡喃并[3,2-A]咔唑
• 中文别名: 柯九里香甲碱
• 英文名称: koenidine
• 英文别名: koenimbidine；Koenigicine；8,9-dimethoxy-3,3,5-trimethyl-11H-pyrano[3,2-a]carbazole
• CAS: 24123-92-0
• 化学式: C₂₀H₂₁NO₃
• 分子量: 323.392
• InChiKey: IUZVYLWUISSZCS-UHFFFAOYSA-N

物化性质

• 熔点：
  224-225 °C
• 沸点：
  500.1±50.0 °C(Predicted)
• 密度：
  1.198
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  43.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26
• 危险类别码：
  R36,R53
• WGK Germany：
  3
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  3,11-二氢-8,9-二甲氧基-3,3,5-三甲基吡喃并[3,2-A]咔唑 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲醇 、 水 为溶剂， 反应 20.0h， 以57%的产率得到8,9-dimethoxy-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazole-5-carbaldehyde
  参考文献：
  名称：

  Pyranocarbazole derivatives as potent anti-cancer agents triggering tubulin polymerization stabilization induced activation of caspase-dependent apoptosis and downregulation of Akt/mTOR in breast cancer cells

  摘要：

  A series of new pyranocarbazole derivatives were synthesized via semi-synthetic modification of koenimbine (la) and koenidine (1b) isolated from the leaves of Murraya koenigii. Among all, compound 3bg displayed significant anti-cancer activity against MDA-MB-231, DU145 and PC3 cell lines with the IC50 values of 3.8, 7.6 and 5.8 mu M, respectively. It was also observed that the halogenated-benzyl substitution at N-9 position, C-3 Methyl and C-7 methoxy group on carbazole motif are favoured for anti-cancer activity. The detailed investigation was carried out with compound 3bg and its SEDDS (self-emulsifying drug delivery systems) formulation 3bgF. The in vivo drug release behavior study showed that the formulation enhanced slow release and better bioavailability at a tumor site. Compound 3bg and its formulation (3bgF) significantly inhibited cell proliferation and colony formation, induced G2/M arrest, reduced cellular ROS generation and induced caspase-dependent apoptosis in MDA-MB-231 cells. 3bg also induced significant alteration of Bax/Bcl expression ratio suggesting involvement of mitochondrial apoptosis. Additionally, 3bg caused down-regulation of mTOR/Akt survival pathway. 3bg do not bind to DNA, but interacts with tubulin as observed with in silico molecular docking studies. This interaction results in stabilization of tubulin polymerization similar to paclitaxel as detected in cell-free assay. Oral administration of 3bgF for 30 days at dose rate of 10 and 20 mg/kg body weight significantly reduced tumor growth in syngenic rat LA-7 mammary tumor model. These results indicated that the pyranocarbazole natural product based N-substituted analogues can act as potential anti-cancer lead. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.02.003
• 作为产物：
  描述：

  2-溴-4,5-二乙氧基苯胺 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 盐酸羟胺 、 四丁基氟化铵 、 potassium carbonate 、 苯基锂 、 正丁胺 、 二异丙胺 、 三苯基膦 、 copper(l) chloride 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 3,11-二氢-8,9-二甲氧基-3,3,5-三甲基吡喃并[3,2-A]咔唑
  参考文献：
  名称：

  Hexadehydro-Diels-Alder (HDDA)-Enabled Carbazolyne Chemistry：Murraya koenigii（咖喱树）家族生物碱的吡并咔唑核的单步、从头构建

  摘要：

  在这里，我们报告了使用六氢-狄尔斯-阿尔德 (HDDA) 反应在稠合的多环杂芳族咔唑（即 [2,3]-苯并吲哚）骨架中从头构建苯环。该策略允许创建高度取代的苯类。我们还描述了天然产物生物碱 mahanimbine 和 koenidine 的 HDDA 化学合成。用共轭烯醛捕获中间体咔唑炔，通过正式的 [2+2] 环加成、4π-电环开环和 6π-电环闭环事件，构成了生产吡并咔唑的可靠方法。

  DOI：

  10.1021/jacs.6b09628

文献信息

• Total synthesis of natural pyrano[3,2-a]carbazole alkaloids
  作者：Shicheng Lu、Wenbin Shang、Ping Yang、Ting Wang、Jinghua Yang、Yunsong Wang

  DOI：10.1016/j.tet.2023.133743

  日期：2023.12

  palladium(II)-catalyzed oxidative cyclization of diphenylamine. In the palladium-catalyzed oxidative cyclization process, this approach successfully circumvents the Wacker oxidation by restricting the involvement of water, ultimately enabling the selective dehydrogenative oxidative cyclization of the C–C bond of the aryl ring. Consequently, this strategy simplifies the complexity of the reaction and reduces the

  报道了一种有效全合成吡喃并[3,2- a ]咔唑生物碱的方法，合成了六种天然吡喃并[3,2- a ]咔唑生物碱，即girinimbine ( 1 )、mukoenine C ( 2 ) 、koenimbine ( 3 )、koenigine ( 4 )、koenine ( 5 ) 和 koenidine ( 6 )。在本研究中，采用容易获得的2-甲基-5-硝基苯酚作为合成氨基色烯的起始材料。通过Buchwald-Hartwig偶联反应生成中间体二苯胺，最终通过分子内钯(II)催化的二苯胺氧化环化促进吡喃并[3,2- a ]咔唑的合成。在钯催化的氧化环化过程中，该方法通过限制水的参与成功地规避了瓦克氧化，最终实现了芳环C-C键的选择性脱氢氧化环化。因此，该策略简化了反应的复杂性并减少了合成步骤。
• Synthesis of the Pyrano[3,2-a]carbazole Alkaloids Koenine, Koenimbine, Koenigine, Koenigicine, and Structural Reassignment of Mukonicine
  作者：Hans-Joachim Knölker、Christian Schuster、Marika Rönnefahrt、Konstanze Julich-Gruner、Anne Jäger、Arndt Schmidt

  DOI：10.1055/s-0035-1560359

  日期：——

  Using the palladium(II)-catalyzed oxidative cyclization of a diarylamine and the annulation of a dimethylpyran ring by Lewis acid promoted reaction with prenal as key steps, the total syntheses of the 6-oxygenated pyrano[3,2-a]carbazole alkaloids koenine and koenimbine, and of the 6,7-dioxygenated pyrano[3,2-a]carbazole alkaloids koenigine and koenigicine (koenimbidine, koenidine) were achieved. Moreover, these studies led to an improved synthetic route to the 2,6-dioxygenated carbazole alkaloid glycozolidol. Mukonicine, originally published as 6,8-dimethoxypyrano[3,2-a]carbazole, was found to be identical with koenigicine.
• One-pot synthesis of the naturally occurring dimeric carbazole alkaloid murranimbine and its analogue
  作者：Mumu Chakraborty、Sibabrata Mukhopadhyay

  DOI：10.1016/j.tetlet.2010.05.030

  日期：2010.7

  Murranimbine, a naturally occurring dimeric carbazole alkaloid, isolated from the root bark of Murraya euchrestfolia was synthesized in one step by the application of Lewis acid (BF3-Et2O) on its monomer girinimbine. A new dimer of koenidine was also synthesized following the same procedure. Structures of these dimeric carbazole alkaloids were determined by detailed spectral analysis. (C) 2010 Elsevier Ltd. All rights reserved.
• Narasimhan,N.S. et al., Indian Journal of Chemistry, 1970, vol. 8, p. 473 - 474
  作者：Narasimhan,N.S. et al.

  DOI：——

  日期：——
• Hexadehydro-Diels–Alder (HDDA)-Enabled Carbazolyne Chemistry: Single Step, de Novo Construction of the Pyranocarbazole Core of Alkaloids of the <i>Murraya koenigii</i> (Curry Tree) Family
  作者：Tao Wang、Thomas R. Hoye

  DOI：10.1021/jacs.6b09628

  日期：2016.10.26

  Here we report the use of the hexadehydro-Diels-Alder (HDDA) reaction for the de novo construction of a benzenoid ring in fused polycyclic heteroaromatic carbazole (i.e., [2,3]-benzoindole) skeletons. The strategy allows creation of highly substituted benzenoids. We also describe the HDDA-enabled chemical synthesis of the natural product alkaloids mahanimbine and koenidine. Trapping of the intermediate

  在这里，我们报告了使用六氢-狄尔斯-阿尔德 (HDDA) 反应在稠合的多环杂芳族咔唑（即 [2,3]-苯并吲哚）骨架中从头构建苯环。该策略允许创建高度取代的苯类。我们还描述了天然产物生物碱 mahanimbine 和 koenidine 的 HDDA 化学合成。用共轭烯醛捕获中间体咔唑炔，通过正式的 [2+2] 环加成、4π-电环开环和 6π-电环闭环事件，构成了生产吡并咔唑的可靠方法。