4,5-dihydro-6,6-dimethyl-6H-2-(4-methylphenyl)-pyrano[b-4,3]naphtho[1,2-d]imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 4,5-dihydro-6,6-dimethyl-6H-2-(4-methylphenyl)-pyrano[b-4,3]naphtho[1,2-d]imidazole
• 英文别名: 6,6-dimethyl-2-(p-tolyl)-3,4,5,6-tetrahydrobenzo[7,8]chromeno[5,6-d]imidazole；4,5-dihydro-6,6-dimethyl-6H-2-(4^,-methylphenyl)-pyran[b-4,3]naphth[1,2-d]imidazole；6,6-Dimethyl-2-(4-methylphenyl)-3,4,5,6-tetrahydrobenzo[7,8]chromeno[5,6-d]imidazole；10,10-dimethyl-4-(4-methylphenyl)-11-oxa-3,5-diazatetracyclo[11.4.0.02,6.07,12]heptadeca-1(17),2(6),4,7(12),13,15-hexaene
• 化学式: C₂₃H₂₂N₂O
• 分子量: 342.44
• InChiKey: GHHJKGHZKBLENT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  二苯基乙炔 、 4,5-dihydro-6,6-dimethyl-6H-2-(4-methylphenyl)-pyrano[b-4,3]naphtho[1,2-d]imidazole 在 silver hexafluoroantimonate 、 [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂ 、 copper(II) acetate monohydrate 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以72%的产率得到3,3,13-trimethyl-10,11-diphenyl-2,3-dihydro-1H-benzo[7′,8′]chromeno[5′,6′:4,5]imidazo[2,1-a]isoquinoline
  参考文献：
  名称：

  钌 (II) 催化的非对称咪唑的 C-H/N-H 炔烃环化：计算和光物理性质的机理见解

  摘要：

  报道了基于由β-拉帕醌和去甲-β-拉帕醌制备的不对称咪唑的Ru(II)催化的炔烃环化反应的π-膨胀策略的实施。我们还研究了光物理方面和计算研究反应的机理，并进行了详细描述和讨论。

  DOI：

  10.1002/ejoc.202200590
• 作为产物：
  描述：

  黄钟花醌 在 乙酸铵 、 硫酸 、 溶剂黄146 作用下， 反应 0.75h， 生成 4,5-dihydro-6,6-dimethyl-6H-2-(4-methylphenyl)-pyrano[b-4,3]naphtho[1,2-d]imidazole
  参考文献：
  名称：

  β-拉帕醌半合成吡喃[b-4,3]萘并[1,2-d]咪唑类杀锥虫活性的研究。

  摘要：

  我们使用苯基和杂环醛从 β-lapachone 合成了新的萘咪唑，其中芳香部分与咪唑环相连。针对克氏锥虫最活跃的化合物有一个与苯环相连的对甲基基团，呈现出 15.5 +/- 2.9 microM 的 EC(50) 值。不能与苯基系列中的生物活性和结构建立可靠的相关性。根据我们之前的工作，对于杂环系列，活性与从氮到咪唑环的三键距离有关。

  DOI：

  10.1016/j.ejmech.2004.02.015

文献信息

• Rhodium(III)-Catalyzed C–H/N–H Alkyne Annulation of Nonsymmetric 2-Aryl (Benz)imidazole Derivatives: Photophysical and Mechanistic Insights
  作者：Gleiston G. Dias、Esther R. S. Paz、Juliana Y. Kadooca、Adão A. Sabino、Luiz A. Cury、Kohei Torikai、Carlos A. de Simone、Felipe Fantuzzi、Eufrânio N. da Silva Júnior

  DOI：10.1021/acs.joc.0c02054

  日期：2021.1.1

  enabled C–H/N–H alkyne annulation of nonsymmetric imidazole derivatives. This study encompasses the synthesis of imidazoles from a naturally occurring quinoidal compound and their use for the preparation of rigid π-extended imidazole derivatives with outstanding fluorescence. Our study also brings to light the photophysical aspects and the mechanism of the reaction studied via computational calculations

  铑（III）催化可实现非对称咪唑衍生物的C–H / N–H炔烃环化。这项研究涵盖了由天然存在的醌型化合物合成咪唑及其在制备具有出色荧光性的刚性π-延伸咪唑衍生物中的用途。我们的研究还揭示了光物理方面以及通过计算计算研究的反应机理。该方法为合成具有多种化学和生物学应用的荧光化合物提供了一种有效且通用的工具。
• Studies on the trypanocidal activity of semi-synthetic pyran[b-4,3]naphtho[1,2-d]imidazoles from β-lapachone
  作者：Kelly C.G De Moura、Kelly Salomão、Rubem F.S Menna-Barreto、Flávio S Emery、Maria do Carmo F.R Pinto、Antônio V Pinto、Solange L de Castro

  DOI：10.1016/j.ejmech.2004.02.015

  日期：2004.7

  We synthesized new naphthoimidazoles from beta-lapachone with an aromatic moiety linked to the imidazole ring, using phenylic and heterocyclic aldehydes. The most active compound against Trypanosoma cruzi had a p-methyl group linked to the phenyl ring, presenting an EC(50) value of 15.5 +/- 2.9 microM. No reliable correlation could be established with the biological activity and the structure of in

  我们使用苯基和杂环醛从 β-lapachone 合成了新的萘咪唑，其中芳香部分与咪唑环相连。针对克氏锥虫最活跃的化合物有一个与苯环相连的对甲基基团，呈现出 15.5 +/- 2.9 microM 的 EC(50) 值。不能与苯基系列中的生物活性和结构建立可靠的相关性。根据我们之前的工作，对于杂环系列，活性与从氮到咪唑环的三键距离有关。
• Mitochondrial disfunction and ROS production are essential for anti-Trypanosoma cruzi activity of β-lapachone-derived naphthoimidazoles
  作者：Ana Cristina S. Bombaça、Paula G. Viana、Augusto C.C. Santos、Thaissa L. Silva、Aline Beatriz M. Rodrigues、Ana Carolina R. Guimarães、Marilia O.F. Goulart、Eufrânio N. da Silva Júnior、Rubem F.S. Menna-Barreto

  DOI：10.1016/j.freeradbiomed.2018.11.012

  日期：2019.1

  Chagas disease is caused by the hemoflagellate protozoa Trypanosoma cruzi and is one of the most important neglected tropical diseases, especially in Latin American countries, where there is an association between low-income populations and mortality. The nitroderivatives used in current chemotherapy are far from ideal and present severe limitations, justifying the continuous search for alternative drugs. Since the 1990s, our group has been investigating the trypanocidal activity of natural naphthoquinones and their derivatives, and three naphthoimidazoles (N1, N2 and N3) derived from beta-lapachone were found to be most effective in vitro. Analysis of their mechanism of action via cellular, molecular and proteomic approaches indicates that the parasite mitochondrion contains one of the primary targets of these compounds, trypanothione synthetase (involved in trypanothione production), which is overexpressed after treatment with these compounds. Here, we further evaluated the participation of the mitochondria and reactive oxygen species (ROS) in the anti-T. cruzi action of naphthoimidazoles. Preincubation of epimastigotes and trypomastigotes with antioxidants (alpha-tocopherol and urate) strongly protected the parasites from the trypanocidal effect of naphthoimidazoles, decreasing the ROS levels produced and reverting the mitochondrial swelling phenotype. The addition of pro-oxidants (menadione and H2O2) before the treatment induced an increase in parasite lysis. Despite the O-2 uptake and mitochondrial complex activity being strongly reduced by N1, N2 and N3, urate partially restored the mitochondrial metabolism only in N1-treated parasites. In parallel, MitoTEMPO, a mitochondrial-targeted antioxidant, protected the functionality of the mitochondria in N2- and N3-treated parasites. In addition, the trypanothione reductase activity was remarkably increased after treatment with N1 and N3, and molecular docking demonstrated that these two compounds were positioned in pockets of this enzyme. Based on our findings, the direct impairment of the mitochondrial electron transport chain by N2 and N3 led to an oxidative misbalance, which exacerbated ROS generation and led to parasite death. Although other mechanisms cannot be discounted, mainly in N1-treated parasites, further investigations are required.
• Novel N,N-di-alkylnaphthoimidazolium derivative of β-lapachone impaired Trypanosoma cruzi mitochondrial electron transport system
  作者：Ana Cristina S. Bombaça、Leonardo A. Silva、Otávio Augusto Chaves、Lorrainy S. da Silva、Juliana M.C. Barbosa、Ari M. da Silva、Aurélio B.B. Ferreira、Rubem F.S. Menna-Barreto

  DOI：10.1016/j.biopha.2020.111186

  日期：2021.3
• Ruthenium(II)‐Catalyzed C−H/N−H Alkyne Annulation of Nonsymmetric Imidazoles: Mechanistic Insights by Computation and Photophysical Properties
  作者：Luana A. Machado、Esther R. S. Paz、Maria H. Araujo、Leandro D. Almeida、Ícaro A. O. Bozzi、Gleiston G. Dias、Cynthia L. M. Pereira、Leandro F. Pedrosa、Felipe Fantuzzi、Felipe T. Martins、Luiz A. Cury、Eufrânio N. da Silva Júnior

  DOI：10.1002/ejoc.202200590

  日期：2022.7.27

  The implementation of a π-expansion strategy based on the Ru(II)-catalyzed alkyne annulation reactions of nonsymmetric imidazoles prepared from β-lapachone and nor-β-lapachone is reported. Photophysical aspects and the mechanism of the computationally studied reaction were also investigated by us and are described and discussed in detail.

  报道了基于由β-拉帕醌和去甲-β-拉帕醌制备的不对称咪唑的Ru(II)催化的炔烃环化反应的π-膨胀策略的实施。我们还研究了光物理方面和计算研究反应的机理，并进行了详细描述和讨论。