5,6,7-trihydroxy-2-[4-[2-(4-morpholinyl)ethoxy]phenyl]-4H-1-benzopyran-4-one | 1436398-09-2

• 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: 5,6,7-trihydroxy-2-[4-[2-(4-morpholinyl)ethoxy]phenyl]-4H-1-benzopyran-4-one
• 英文别名: 5,6,7-trihydroxy-2-(4-(2-morpholinoethoxy)phenyl)-4H-chromen-4-one；5,6,7-Trihydroxy-2-[4-(2-morpholin-4-ylethoxy)phenyl]chromen-4-one；5,6,7-trihydroxy-2-[4-(2-morpholin-4-ylethoxy)phenyl]chromen-4-one
• CAS: 1436398-09-2
• 化学式: C₂₁H₂₁NO₇
• 分子量: 399.4
• InChiKey: PANBLRFOYVHJJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  野黄芩素 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 溶剂黄146 、 potassium iodide 作用下， 以 四氢呋喃 、 二苯醚 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 175.0 ℃ 、101.33 kPa 条件下， 反应 48.0h， 生成 5,6,7-trihydroxy-2-[4-[2-(4-morpholinyl)ethoxy]phenyl]-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

文献信息

• 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.
• 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。