4-(氯甲基)-5,7-二羟基-2H-苯并吡喃-2-酮 | 809234-33-1

• 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
• 中文名称: 4-(氯甲基)-5,7-二羟基-2H-苯并吡喃-2-酮
• 英文名称: 4-chloromethyl-5,7-dihydroxy-chromen-2-one
• 英文别名: 4-(chloromethyl)-5,7-dihydroxy-2H-1-benzopyran-2-one；4-(chloromethyl)-5,7-dihydroxy-2H-chromen-2-one；4-chloromethyl-5,7-dihydroxy-2H-chromen-2-one；4-chloromethyl-5,7-dihydroxyl-coumarin；4-chloromethyl-5-hydroxyumbelliferone；4-chloromethyl-5,7-dihydroxycoumarin；4-(chloromethyl)-5,7-dihydroxychromen-2-one
• CAS: 809234-33-1
• 化学式: C₁₀H₇ClO₄
• 分子量: 226.616
• InChiKey: SMMCGQQUJPNVBJ-UHFFFAOYSA-N

物化性质

• 熔点：
  243-245 °C(Solv: ethanol (64-17-5))
• 沸点：
  499.7±33.0 °C(Predicted)
• 密度：
  1.569±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2932209090

制备方法与用途

DNA聚合酶-IN-1（化合物2d）是一种DNA聚合酶抑制剂，其IC50值为20.7 μM，并且对肿瘤细胞具有抗增殖活性。

反应信息

• 作为反应物：
  描述：

  4-(氯甲基)-5,7-二羟基-2H-苯并吡喃-2-酮 在 sodium azide 作用下， 以 乙腈 为溶剂， 反应 10.0h， 以76%的产率得到4-(azidomethyl)-5,7-dihydroxy-2H-chromen-2-one
  参考文献：
  名称：

  Synthesis and biological evaluation of coumarin–1,2,3-triazole–dithiocarbamate hybrids as potent LSD1 inhibitors

  摘要：

  将新型香豆素-1,2,3-三唑-二硫代氨基甲酸酯混合物设计为强效LSD1抑制剂，通过引入香豆素骨架。

  DOI：

  10.1039/c4md00031e
• 作为产物：
  描述：

  间苯三酚 、 4-氯乙酰乙酸甲酯 在 aluminum oxide 、 甲烷磺酸 作用下， 反应 0.25h， 以94%的产率得到4-(氯甲基)-5,7-二羟基-2H-苯并吡喃-2-酮
  参考文献：
  名称：

  Al2O3/MeSO3H (AMA) as a novel heterogeneous system for synthesis of coumarins under mild conditions

  摘要：

  Al2O3/MeSO3H (AMA) is found to be an efficient reagent for the Pechman condensation reaction of phenols and beta- ketoesters under solvent free conditions. The reaction protocol is simple, cost- effective, solvent free and gives good isolated yield with high purity and good regioselectivity.

  DOI：

  10.1016/s0385-5414(07)81208-1

文献信息

• Alternative two-step route to khellactone analogues using silica tungstic acid and sodium hydrogen phosphate
  作者：Bahador Karami、Saeed Khodabakhshi、Khalil Eskandari

  DOI：10.2478/s11696-013-0411-z

  日期：2013.1.1

  A series of coumarins was synthesised via the silica tungstic acid-catalysed Pechmann reaction; some of these were employed for known three-component reactions with aromatic aldehydes and malononitrile in the presence of sodium hydrogen phosphate (Na2HPO4) as a basic catalyst, affording a variety of potentially anti-HIV active khellactone analogues.

  一系列香豆素通过硅钨酸催化的Pechmann反应合成；其中一些用于已知的三组分反应，与芳香醛和马来酸二腈在存在磷酸氢钠（Na2HPO4）作为碱性催化剂的情况下，生成各种潜在的抗HIV活性的赤花内酯类似物。
• Chemical Library and Structure–Activity Relationships of 11-Demethyl-12-oxo Calanolide A Analogues as Anti-HIV-1 Agents
  作者：Tao Ma、Li Liu、Hai Xue、Li Li、Chunyan Han、Lin Wang、Zhiwei Chen、Gang Liu

  DOI：10.1021/jm701405p

  日期：2008.3.13

  (+)-Calanolide A (1) as a natural product was previously found as an inhibitor of HIV-1 reverse tratiscriptase. In our further investigation of its template, racemic 11-demethyl-12-oxo calanolide A (15), which had two fewer chiral carbon centers at the C-11 and C-12 positions than (+)-calanolide A, had a comparably inhibitory activity and better therapeutic index (EC(50) = 0.11 mu M, TI = 818) against HIV-1 in vitro. A library based on its structural core was then designed and synthesized with introduction of nine diversity points in this article. The evaluations of anti-HIV-1 activity in vitro concluded their structure-activity relationships (SARs). A novel compound (10-bromomethyl-11-demethyl-12-oxo calanolide A, 123) was identified to have much higher inhibitory potency and therapeutic index (EC(50) = 2.85 nM, TI > 10,526) than those of the class compound against HIV-1. This finding provided a very important clue that modifications of the C ring at the C-10 position may be conducted to obtain drug candidates with better activity against HIV-1.

  (+)-Calanolide A (1) 作为一种天然产物，先前被发现是HIV-1逆转录酶的抑制剂。在我们对其模板的进一步研究中，外消旋的11-去甲基-12-酮基calanolide A (15) 被发现。与(+)-calanolide A相比，它在C-11和C-12位上少两个手性碳中心，但其对HIV-1的抑制活性相当，并且具有更好的治疗指数（EC(50) = 0.11 μM，TI = 818）。随后，基于其结构核心设计并合成了一个化合物库，并在本文中引入了九个多样性点。体外评估抗HIV-1活性得出了它们的结构-活性关系（SARs）。发现了一个新的化合物（10-溴甲基-11-去甲基-12-酮基calanolide A，123），其对HIV-1的抑制效力和治疗指数（EC(50) = 2.85 nM，TI > 10,526）显著高于该类化合物。这一发现提供了非常重要的线索，即对C环的C-10位进行修饰，可能会得到对HIV-1活性更好的药物候选物。
• Nano-Fe₃O₄@SiO₂-supported boron sulfonic acid as a novel magnetically heterogeneous catalyst for the synthesis of pyrano coumarins
  作者：Mahnaz Farahi、Bahador Karami、Raziyeh Keshavarz、Foroogh Khosravian

  DOI：10.1039/c7ra08253c

  日期：——

  magnetically heterogeneous catalyst based on the immobilization of boron sulfonic acid onto Fe3O4@SiO2 nanoparticles (Fe3O4@SiO2–BSA) is reported. Fe3O4@SiO2–BSA was characterized via FT-IR, X-ray diffraction patterns (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and vibrating sample magnetometer (VSM) analysis. The performance ability of this catalyst including

  在这项研究中，报道了一种基于硼磺酸固定在Fe 3 O 4 @SiO 2纳米颗粒（Fe 3 O 4 @SiO 2 -BSA）上的新型磁性非均相催化剂。Fe 3 O 4 @SiO 2 –BSA通过FT-IR，X射线衍射图（XRD），扫描电子显微镜（SEM），能量色散X射线光谱（EDS）和振动样品磁力计（VSM）分析。在无溶剂条件下以高收率评估了该催化剂包括酸位点的性能，以合成吡喃香豆素。催化剂的热稳定性及其易于被磁场分离，使该催化剂成为良好的多相体系，并且是其他多相催化剂的有用替代品。
• Gastroprotective activity of synthetic coumarins: Role of endogenous prostaglandins, nitric oxide, non-protein sulfhydryls and vanilloid receptors
  作者：Beatriz Sepulveda、Cristina Quispe、Mario Simirgiotis、Alfredo Torres-Benítez、Johanna Reyes-Ortíz、Carlos Areche、Olimpo García-Beltrán

  DOI：10.1016/j.bmcl.2016.10.056

  日期：2016.12

  Natural or synthetic coumarins showed gastroprotective and antiulcer activity in animal models. In this study, we have synthetized twenty coumarins using classic methods to evaluate their gastroprotective effects on the ethanol/HCl-induced gastric lesion model in mice at 20mg/kg. Among the coumarins synthetized, compounds 6 and 10 showed the greatest gastroprotective activity being as active as lansoprazole

  天然或合成香豆素在动物模型中显示出胃保护和抗溃疡活性。在这项研究中，我们已经使用经典方法合成了20种香豆素，以评估它们对20mg / kg的乙醇/ HCl诱导的小鼠胃部病变模型的胃保护作用。在合成的香豆素中，化合物6和10表现出最大的胃保护活性，在20mg / kg的条件下，其活性与兰索拉唑相同，分别减少了75％和76％的胃部损害。然后，在第二个实验中，对化合物6和10进行了重新评估，以了解其胃保护活性的可能模式。关于香豆素6，通过用N-乙基马来酰亚胺和l-NAME预处理小鼠降低了保护作用，表明巯基化合物和内源性一氧化氮参与了其胃保护活性。
• An efficient procedure for the synthesis of coumarin derivatives using TiCl4 as catalyst under solvent-free conditions
  作者：Hassan Valizadeh、Abbas Shockravi

  DOI：10.1016/j.tetlet.2005.03.124

  日期：2005.5

  titanium(IV) chloride as a catalyst to promote the Pechmann condensation reaction with a range of phenols and β-keto esters is described.The reaction was carried out by addition of TiCl4 to a mixture of the phenol and the β-keto ester with thorough stirring in the absence of a solvent and represents an improvement on the classical Pechmann conditions. The yields of coumarins obtained via this novel protocol

  描述了氯化钛（IV）催化与一系列酚和β-酮酸酯进行Pechmann缩合反应的能力。该反应是通过将TiCl 4添加到酚和β-酮的混合物中进行的在没有溶剂的情况下充分搅拌下得到的酮酸酯，代表了对经典Pechmann条件的改进。通过该新颖方案获得的香豆素的产率明显高于使用常规方法的香豆素的产率，并且反应持续时间减少至数分钟甚至数秒。