6-(4-(benzyloxy)phenyl)-9-hydroxy-2,2-diphenyl-8H-[1,3]dioxolo[4,5-g]chromen-8-one | 1402607-40-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 6-(4-(benzyloxy)phenyl)-9-hydroxy-2,2-diphenyl-8H-[1,3]dioxolo[4,5-g]chromen-8-one
• 英文别名: 9-Hydroxy-2,2-diphenyl-6-(4-phenylmethoxyphenyl)-[1,3]dioxolo[4,5-g]chromen-8-one；9-hydroxy-2,2-diphenyl-6-(4-phenylmethoxyphenyl)-[1,3]dioxolo[4,5-g]chromen-8-one
• CAS: 1402607-40-2
• 化学式: C₃₅H₂₄O₆
• 分子量: 540.572
• InChiKey: MTCFWSJZILSPRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(4-(benzyloxy)phenyl)-9-hydroxy-2,2-diphenyl-8H-[1,3]dioxolo[4,5-g]chromen-8-one 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 水 、 丙酮 为溶剂， 反应 15.5h， 生成 5-hydroxy-2-(4-hydroxyphenyl)-6,7-bis(methoxymethoxy)-4H-1-benzopyran-4-one
  参考文献：
  名称：

  Efficient Chemical Synthesis of a Scutellarein Derivative Containing Morpholine Ring

  摘要：

  黄芩苷（1）[5,6-二羟基-2-（4-羟基苯基）-4-氧代-4H-1-苯并吡喃-7-基 β-D-吡喃葡萄糖苷酸]在我国临床治疗脑梗塞和冠心病方面疗效显著。药代动力学研究表明，黄芩苷（1）在吸收前很容易在肠道中被β-葡萄糖醛酸酶代谢为黄芩苷（2）[5,6,7-三羟基-2-（4-羟基苯基）-4H-1-苯并吡喃-4-酮]。为了提高黄芩苷（1）的生物活性，我们课题组根据其体内代谢机制合成了多种黄芩苷衍生物。结果表明，与黄芩苷（1）相比，C-7 或 C-8 位取代的吗啉环具有更好的抗氧化活性、水溶性和抗凝血活性。本文报告了一种构建 5,6,7-三羟基-2-[4-[2-(4-吗啉基)乙氧基]苯基]-4H-1-苯并吡喃-4-酮（5）的高效合成方法。 该合成路线将促进在 C- 4'位置含有胺侧链的黄芩苷衍生物的合成。

  DOI：

  10.2174/1570178611666140421230118
• 作为产物：
  描述：

  野黄芩素 在 potassium carbonate 作用下， 以 二苯醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 6-(4-(benzyloxy)phenyl)-9-hydroxy-2,2-diphenyl-8H-[1,3]dioxolo[4,5-g]chromen-8-one
  参考文献：
  名称：

  黄cut苷烷基衍生物的合成及其生物学评估，可预防脂质变性，改善神经退行性疾病。

  摘要：

  背景技术外源性抗氧化剂被认为是治疗神经退行性疾病的有前途的治疗方法，因为它们可以预防和/或最小化氧化引起的神经元损害。目的设计并合成了基于黄cut苷（2）的结构上的三系列亲脂性化合物，黄re苷（2）是黄cut苷（1）在体内的一种代谢产物。方法通过检测亚铁盐/抗坏血酸诱导的脂质自氧化产生的2-硫代巴比妥酸反应性物质（TBARS）来评估其抗氧化活性，所述脂质存在于大鼠肝细胞的微粒体膜中。用紫外（UV）分光光度计研究了表示为正辛醇和缓冲液之间分配系数的这些化合物的亲脂性。结果该研究表明在C4'-OH位置被苄基取代的化合物5e表现出强的抗氧化活性和良好的亲脂性。结论5e可能是预防或减少与神经退行性过程相关的氧化状态的有效候选者。

  DOI：

  10.2174/1573406414666181015143551

文献信息

• Efficient Synthesis of 6-O-methyl-scutellarein from Scutellarin via Selective Methylation
  作者：Min-Zhe Shen、Zhi-Hao Shi、Nian-Guang Li、Hao -Tang、Qian-Ping Shi、Yu-Ping Tang、Jian-Ping Yang、Jin-Ao Duan

  DOI：10.2174/15701786113109990046

  日期：2013.11

  Scutellarin (1) possesses distinguished efficacy in the clinical therapy of cerebral infarction, coronary heart disease, and angina pectoris. Scutellarin (1) is readily converted in vivo, therefore, synthetic methods for the construction of its metabolites will be very important in the near future. In this work, an efficient and first synthetic method for 6-O-methyl- scutellarein (3), one metabolite of scutellarin in vivo, is developed. Dichlorodiphenylmethane in diphenyl ether is used firstly to protect the dihydroxy groups at C-6 and C-7 in scutellarein (2). Then, benzyl bromide is used to selectively protect the hydroxy groups at C-4' and C-7 in 10. 6-O-Methyl-scutellarein (3) is obtained in high yield through seven steps.

  黄芩苷（1）在脑梗塞、冠心病和心绞痛的临床治疗中具有显著疗效。黄芩苷（1）在体内很容易转化，因此，合成其代谢物的方法在不久的将来将非常重要。在这项工作中，首次开发出了黄芩苷的一种代谢物--6-O-甲基黄芩苷（3）的高效合成方法。首先用二苯醚中的二氯二苯甲烷保护黄芩苷（2）中 C-6 和 C-7 的二羟基。然后用溴化苄选择性地保护 10 中 C-4' 和 C-7 的羟基。通过七个步骤，便可高产获得 6-O-甲基黄芩苷（3）。
• Synthesis of scutellarein derivatives to increase biological activity and water solubility
  作者：Zhi-Hao Shi、Nian-Guang Li、Qian-Ping Shi、Wei Zhang、Ze-Xi Dong、Yu-Ping Tang、Peng-Xuan Zhang、Ting Gu、Wen-Yu Wu、Fang Fang、Xin-Xue、He-Min Li、Jian-Ping Yang、Jin-Ao Duan

  DOI：10.1016/j.bmc.2015.09.047

  日期：2015.11

  In order to improve the biological activity and water solubility of scutellarin (1), some derivatives of its main metabolite (scutellarein) were designed and synthesized. All the compounds were tested for their thrombin inhibition activity through the analyzation of thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity, their water solubility were also assessed by ultraviolet (UV) spectrophotometer. The results showed that compound 8b demonstrated stronger anticoagulant and antioxidant activity, better water solubility compared with scutellarein (2), which warrants it as a promising agent for the treatment of ischemic cerebrovascular disease. (C) 2015 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of methylated scutellarein analogs based on metabolic mechanism of scutellarin in vivo
  作者：Zhi-Hao Shi、Nian-Guang Li、Zhen-Jiang Wang、Yu-Ping Tang、Ze-Xi Dong、Wei Zhang、Peng-Xuan Zhang、Ting Gu、Wen-Yu Wu、Jian-Ping Yang、Jin-Ao Duan

  DOI：10.1016/j.ejmech.2015.10.039

  日期：2015.12

  Scutellarin (1) could be hydrolyzed into scutellarein (2) in vivo and then converted into methylated, sulfated and glucuronidated forms. In order to investigate the biological activities of these methylated metabolites, eight methylated analogs of scutellarein (2) were synthesized via semi-synthetic methods. The antithrombotic activities of these compounds were evaluated through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity. Furthermore, the physicochemical properties of these compounds including aqueous solubility and lipophilicity were also investigated. The results showed that 6-O-methylscutellarein (5) demonstrated potent antithrombotic activity, stronger antioxidant activity and balanced solubility and permeability compared with scutellarin (1), which warrants further development of 5 as a promising lead for the treatment of ischemic cerebrovascular disease. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Efficient Chemical Synthesis of a Scutellarein Derivative Containing Morpholine Ring
  作者：Qian-Ping Shi、Zhi-Hao Shi、Nian-Guang Li、Yu-Ping Tang、Hao- Tang、Wei Zhang、Min-Zhe Shen、Ze-Xi Dong、Peng-Xuan Zhang、Jian-Ping Yang、Jin-Ao Duan

  DOI：10.2174/1570178611666140421230118

  日期：2014.6

  Scutellarin (1) [5,6-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-1-benzopyran-7-yl β-D-glucopyranosiduronic acid] is very effective in the clinical treatment of cerebral infarction and coronary heart disease in China. Pharmacokinetic studies showed that scutellarin (1) is readily metabolized to scutellarein (2) [5,6,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1- benzopyran-4-one] in the intestine by β-glucuronide enzyme prior to absorption. In order to improve the biological activity of scutellarin (1), our group has previously synthesized many scutellarin derivatives based on their in vivo metabolic mechanism. The results showed that morpholine ring substituted at C-7 or C-8 position induced better antioxidant activity, water solubility and anticoagulant activity compared to scutellarin (1). In this paper, an efficient synthetic method for the construction of 5,6,7-trihydroxy-2-[4-[2-(4-morpholinyl)ethoxy]phenyl]-4H-1-benzopyran-4-one (5) is reported. This synthetic route will facilitate the synthesis of scutellarein derivatives containing an amine side chain at the C- 4' position.

  黄芩苷（1）[5,6-二羟基-2-（4-羟基苯基）-4-氧代-4H-1-苯并吡喃-7-基 β-D-吡喃葡萄糖苷酸]在我国临床治疗脑梗塞和冠心病方面疗效显著。药代动力学研究表明，黄芩苷（1）在吸收前很容易在肠道中被β-葡萄糖醛酸酶代谢为黄芩苷（2）[5,6,7-三羟基-2-（4-羟基苯基）-4H-1-苯并吡喃-4-酮]。为了提高黄芩苷（1）的生物活性，我们课题组根据其体内代谢机制合成了多种黄芩苷衍生物。结果表明，与黄芩苷（1）相比，C-7 或 C-8 位取代的吗啉环具有更好的抗氧化活性、水溶性和抗凝血活性。本文报告了一种构建 5,6,7-三羟基-2-[4-[2-(4-吗啉基)乙氧基]苯基]-4H-1-苯并吡喃-4-酮（5）的高效合成方法。 该合成路线将促进在 C- 4'位置含有胺侧链的黄芩苷衍生物的合成。
• Synthesis and Biological Evaluation of Scutellarein Alkyl Derivatives as Preventing Neurodegenerative Agents with Improved Lipid Soluble Properties
  作者：He-Min Li、Ting Gu、Wen-Yu Wu、Shao-Peng Yu、Tian-Yuan Fan、Yue Zhong、Nian-Guang Li

  DOI：10.2174/1573406414666181015143551

  日期：2019.10.14

  designed and synthesized. METHODS Their antioxidant activity was evaluated by detecting the 2-thiobarbituric acid reactive substance (TBARS) produced in the ferrous salt/ascorbate-induced autoxidation of lipids, which were present in microsomal membranes of rat hepatocytes. The lipophilicity of these compounds indicated as partition coefficient between n-octanol and buffer was investigated by ultraviolet

  背景技术外源性抗氧化剂被认为是治疗神经退行性疾病的有前途的治疗方法，因为它们可以预防和/或最小化氧化引起的神经元损害。目的设计并合成了基于黄cut苷（2）的结构上的三系列亲脂性化合物，黄re苷（2）是黄cut苷（1）在体内的一种代谢产物。方法通过检测亚铁盐/抗坏血酸诱导的脂质自氧化产生的2-硫代巴比妥酸反应性物质（TBARS）来评估其抗氧化活性，所述脂质存在于大鼠肝细胞的微粒体膜中。用紫外（UV）分光光度计研究了表示为正辛醇和缓冲液之间分配系数的这些化合物的亲脂性。结果该研究表明在C4'-OH位置被苄基取代的化合物5e表现出强的抗氧化活性和良好的亲脂性。结论5e可能是预防或减少与神经退行性过程相关的氧化状态的有效候选者。