3-benzamidocoumarin | 2549-08-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 3-benzamidocoumarin
• 英文别名: 3-benzoylaminocoumarin；N-(2-oxo-2H-chromen-3-yl)benzamide；3-N-benzoylaminocoumarin；N-(2-oxochromen-3-yl)benzamide
• CAS: 2549-08-8
• 化学式: C₁₆H₁₁NO₃
• mdl: MFCD00426633
• 分子量: 265.268
• InChiKey: RXHSXTPNFVSJKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-benzamidocoumarin 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以55.5%的产率得到3-氨基香豆素
  参考文献：
  名称：

  Kumar, Pradeep; Mukerjee, Arya K., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 8, p. 704 - 707

  摘要：

  DOI：
• 作为产物：
  描述：

  2-phenyl-4-salicyliden-4H-oxazol-5-one 在 1-butyl-3-methylimidazolium hydroxide 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 3-benzamidocoumarin
  参考文献：
  名称：

  A one-pot [Bmim]OH-mediated synthesis of 3-benzamidocoumarins

  摘要：

  The first example of an ionic liquid-promoted one-pot synthesis of 3-benzamidocoumarins from salicylaldehydes and 2-pheny-1,3-oxazolan-5-one via Knoevenagel condensation-ring transformation cascades has been reported. No by-product formation, operational simplicity, ambient temperature and high yield (85-97%) are the salient features of the present synthetic protocol. After isolation of the product, the ionic liquid, [Bmim]OH can be easily recycled for further use without any loss of efficiency. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.02.166

文献信息

• Evaluation of Trypanocidal and Antioxidant Activities of a Selected Series of 3-amidocoumarins
  作者：Mauricio Moncada-Basualto、Michel Lapier、Juan Diego Maya、Betty Matsuhiro、Claudio Olea-Azar、Giovanna L. Delogu、Eugenio Uriarte、Lourdes Santana、Maria Joao Matose

  DOI：10.2174/1573406414666180419113437

  日期：2018.7.12

  Background: Neglected diseases are becoming more prevalent due to globalization. This has inspired active research in the development of new drugs for the treatment of parasitic diseases such as Chagas disease. Objectives: With the aim of finding new trypanocidal agents, we report the in vitro evaluation of a new series of 3-amidocoumarins with or without hydroxyl substituents at position 4 of the coumarin ring. Methods: Electrochemical and biological assays were performed in order to assess the antioxidant and trypanocidal potential of these compounds and to better understand the mechanisms involved in their activity. Results: Most of the studied compounds showed high trypanocidal activity against both epimastigote and trypomastigote forms, with IC50 values in the low micromolar range. Some of them have greater activity and selectivity than the reference compound, nifurtimox. Conclusion: Compound 2 is the most active of this series, being also non-cytotoxic against murine RAW 264.7 macrophages. Electrochemical and radical scavenging experiments were carried out, providing new information about the profile of the best derivatives, and the potential therapeutic application of the new 3-amidocoumarins.

  背景：由于全球化，被忽视的疾病变得越来越普遍。这激发了针对恰加斯病等寄生虫病治疗新药开发的活跃研究。 目的：为了寻找新的杀锥虫剂，我们报告了一系列新型3-酰胺香豆素（有无羟基取代基在香豆素环的4位）的体外评估。 方法：进行了电化学和生物学测试，以评估这些化合物的抗氧化和杀锥虫潜力，并更好地理解其活性涉及的机制。 结果：大多数研究化合物对epimastigote和trypomastigote形式都显示出高度的杀锥虫活性，IC50值在低微摩尔范围内。其中一些化合物比参考化合物硝呋莫司具有更高的活性和选择性。 结论：化合物2是该系列中最活跃的，对小鼠RAW 264.7巨噬细胞也没有细胞毒性。进行了电化学和自由基清除实验，为最佳衍生物的特性提供了新的信息，并展示了新型3-酰胺香豆素的潜在治疗应用。
• Rhodium‐Catalyzed Asymmetric Hydrogenation of 3‐Benzoylaminocoumarins for the Synthesis of Chiral 3‐Amino Dihydrocoumarins
  作者：Yunnan Xu、Delong Liu、Yu Deng、Yi Zhou、Wanbin Zhang

  DOI：10.1002/anie.202110286

  日期：2021.10.25

  An asymmetric hydrogenation of 3-benzoylaminocoumarins was achieved for the first time using our BridgePhos-Rh catalytic system, providing chiral 3-amino dihydrocoumarins in high yields (up to 98 %) and with excellent enantioselectivities (up to 99.7 % ee). The relationship between the enantioselectivities of the hydrogenations and the dihedral angles and the resulting π-π stacking effects of the BridgePhos-Rh

  使用我们的 BridgePhos-Rh 催化系统首次实现了 3-苯甲酰氨基香豆素的不对称氢化，以高产率（高达 98%）和优异的对映选择性（高达 99.7% ee）提供手性 3-氨基二氢香豆素。讨论了氢化的对映选择性和二面角之间的关系以及由此产生的 BridgePhos-Rh 配合物的 π-π 堆叠效应，这些关系是通过 X 射线衍射分析确定的。相应的氢化产物可以进行多种转化，从而提供多种具有重要生理和药理活性的手性骨架。
• Base-Mediated Cascade Cyclization: Stereoselective Synthesis of Benzooxazocinone
  作者：Chiranan Pramthaisong、Rattana Worayuthakarn、Vannapha Pharikronburee、Tanwawan Duangthongyou、Ramida Rattanakam、Somsak Ruchirawat、Nopporn Thasana

  DOI：10.1021/acs.orglett.8b01573

  日期：2018.7.6

  the synthesis of the oxa-azabicyclo[3.3.1]nonane subunit, a component of the naucleamide E core structure, has been developed. This annulation reaction between 1-substituted 3,4-dihydroisoquinolines and coumarin derivatives conveniently affords the oxa-azabicyclo[3.3.1]nonane framework via a base-mediated cascade cyclization under aqueous conditions. The value of this work lies in the efficient formation

  已开发出一种新的合成策略，合成氧杂氮杂双环[3.3.1]壬烷亚基（一种核酰胺E核心结构的组成部分）。1-取代的3,4-二氢异喹啉与香豆素衍生物之间的环化反应可在水溶液条件下通过碱介导的级联环化方便地提供氧杂氮杂双环[3.3.1]壬烷骨架。这项工作的价值在于通过一种过程有效地形成氧杂氮杂双环[3.3.1]壬烷骨架，该过程中，所有的C–C，C–O和C–N键的形成均在一次化学操作中发生。另外，这些化合物的随后开环提供了吡啶基异喹啉衍生物。
• Copper-Mediated C–O/C–N Bond Formation: A Facile Synthesis of 3-Amidocoumarin, 3-Amidoazacoumarin, and N-Aroylindole ­Derivatives
  作者：Nopporn Thasana、Rattana Worayuthakarn、Nattanit Suddee、Prattya Nealmongkol、Somsak Ruchirawat

  DOI：10.1055/a-1784-1973

  日期：2022.9

  Three different heterocyclic systems (3-amidocoumarins, 3-amidoazacoumarins, and N-benzoylindol-2-carboxamides) were synthesized based on the strikingly different selectivity of copper-mediated C–O/C–N bond formation from azlactones under various heating conditions. The stereochemistry of the double bond dictated the nature of the products. Microwave irradiation played an important role in the isomerization

  基于铜介导的吖内酯在不同加热条件下形成 C-O/C-N 键的选择性明显不同，合成了三种不同的杂环系统（3-酰胺基香豆素、3-酰胺氮杂香豆素和N-苯甲酰吲哚-2-甲酰胺）。双键的立体化学决定了产物的性质。微波辐照在三取代烯烃的异构化中起重要作用，导致形成 3-酰氨基香豆素和 3-酰氨基氮杂香豆素。三种产品对一组癌细胞系显示出良好的细胞毒活性，包括 HepG2（肝母细胞瘤）和 MOLT-3（T 淋巴细胞急性淋巴细胞白血病）。
• 3-Amidocoumarins as Potential Multifunctional Agents against Neurodegenerative Diseases
  作者：Maria João Matos、Fernanda Rodríguez-Enríquez、Fernanda Borges、Lourdes Santana、Eugenio Uriarte、Martín Estrada、María Isabel Rodríguez-Franco、Reyes Laguna、Dolores Viña

  DOI：10.1002/cmdc.201500408

  日期：2015.12

  cell death, causing neurodegeneration. Agents that are able to concurrently inhibit MAO and scavenge free radicals represent promising multifunctional neuroprotective agents that could be used to delay or slow the progression of neurodegenerative diseases. In this work, variously substituted 3‐amidocoumarins are described that exert neuroprotection in vitro against hydrogen peroxide in rat cortical neurons

  单胺氧化酶（MAO）产生活性氧（ROS），导致神经元细胞死亡，导致神经退行性变。能够同时抑制MAO和清除自由基的药物代表了有前途的多功能神经保护剂，可用于延迟或减缓神经退行性疾病的发展。在这项工作中，描述了各种取代的3-氨基豆香豆素，它们在体外对大鼠皮层神经元中的过氧化氢具有神经保护作用，并且在1,1-二苯基-2-picylhydrazyl（DPPH⋅）自由基清除试验中具有抗氧化活性。确定了MAO-B同工型的选择性和可逆抑制剂。有趣的是，对于3-苯甲酰胺基香豆素，在4位被羟基取代会消除MAO-B活性，但这些化合物在神经保护模型中仍然具有活性。对3-杂芳基酰胺衍生物的进一步评估表明，杂环的性质决定了神经保护作用。在平行人工膜通透性试验（PAMPA）中进行的评估强调了进一步改善此类化合物的血脑屏障通透性的需要。然而，本文所述的化合物遵守Libinski的5法则，表明该新型支架具有潜在的候选药物