4-甲氧基-7-甲基吡喃并[3,4-f][1]苯并呋喃-5-酮 | 116408-80-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异香豆素及其衍生物
• 中文名称: 4-甲氧基-7-甲基吡喃并[3,4-f][1]苯并呋喃-5-酮
• 英文名称: coriandrin
• 英文别名: 4-methoxy-7-methylfuro[2,3-g]isochromen-5-one
• CAS: 116408-80-1
• 化学式: C₁₃H₁₀O₄
• 分子量: 230.22
• InChiKey: BUZQIMYNOWPYHH-UHFFFAOYSA-N

物化性质

• 物理描述：
  Solid
• 熔点：
  142-143°C

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  48.7
• 氢给体数：
  0
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	3-methyl-9-hydroxyfuroisocoumarin	157435-98-8	C12H8O4	216.193

反应信息

• 作为反应物：
  描述：

  碘化甲烷-14C 、 4-甲氧基-7-甲基吡喃并[3,4-f][1]苯并呋喃-5-酮 在 三氯化铝 、 potassium carbonate 作用下， 以 硝基苯 、 丙酮 为溶剂， 反应 24.25h， 生成
  参考文献：
  名称：

  Mechanism-Based Inactivation of Hepatic Ethoxyresorufin O-Dealkylation Activity by Naturally Occurring Coumarins

  摘要：

  Several naturally occurring coumarins contained in the human diet have been found to be effective inhibitors and inactivators of murine hepatic ethoxyresorufin O-dealkylase (EROD) and pentoxyresorufin O-dealkylase in vitro [Cai, Y., Bennett, D., Nair, R. V., Ceska, O., Ashwood-Smith, M., and DiGiovanni, J. (1993) Chem. Res. Toxicol. 6, 872-879]. In the present study, these same coumarins decreased the content of: cytochrome P450 (P450) in either 3-methylcholanthrene (MC)- or phenobarbital-induced murine hepatic microsomes but did not have a major effect on heme content. Detailed in vitro studies with [C-14]coriandrin, which selectively inhibits and inactivates P450 1A1-mediated EROD activity, demonstrated that it covalently bound, in a preferential manner, to hepatic microsomal protein from MC-pretreated mice. A linear relationship was observed between covalent binding and loss of EROD activity. The inclusion of electrophile trapping agents in the incubations significantly inhibited the covalent binding of [C-14]coriandrin to microsomal protein. In addition, the covalent binding of [C-14]coriandrin was decreased 46% by 7,8-benzoflavone (7,8-BF), 58% by a monoclonal antibody with specificity toward MC-induced form(s) of P450, and 60% by ethoxyresorufin, implicating the bioactivation of coriandrin by P450 1A1. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [C-14]coriandrin-bound microsomal protein from MC-pretreated mice showed that [C-14]coriandrin bound covalently to a protein with an approximate molecular mass of 49 kDa. Again, addition of 7,8-BF or polyclonal antibody against P450 1A1 reduced the covalent binding of [C-14]coriandrin to this specific protein band. Interestingly, coriandrin was also found to be a potent inhibitor and inactivator of purified human P450 1A1. These results demonstrate that certain coumarins to which humans are exposed in the diet are bioactivated by P450 1A1 to reactive intermediates that subsequently form covalent adducts with the apoprotein, effectively destroying enzyme activity. Thus, certain naturally occurring coumarins may have a significant effect on human health.

  DOI：

  10.1021/tx950208b
• 作为产物：
  描述：

  methyl 4-acetoxy-6-(bromomethyl)benzofuran-5-carboxylate 在 trans-benzyl(chloro)-bis(triphenylphosphine)palladium(II) 双(乙腈)氯化钯(II) 、 lithium hydroxide 、 sodium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 六甲基磷酰三胺 、 水 为溶剂， 反应 56.0h， 生成 4-甲氧基-7-甲基吡喃并[3,4-f][1]苯并呋喃-5-酮
  参考文献：
  名称：

  Total Synthesis of Coriandrin

  摘要：

  Coriandrin, an antiviral agent, has been synthesized in nine steps from diketone 3. The key steps in the synthesis include an efficient aromatization reaction using N-bromosuccinimide and a palladium-mediated coupling of a benzylic bromide with a vinyl stannane.

  DOI：

  10.1021/jo00096a013

文献信息

• Total synthesis of coriandrin and 7-demethylcoriandrin via a new synthesis of isocoumarins
  作者：Dipakranjan Mal、Mousumi Bandyopadhyay、Sujit K Ghorai、Kalyani Datta

  DOI：10.1016/s0040-4039(00)00441-x

  日期：2000.5

  Indenone epoxides 8, prepared from the corresponding indenones, have been shown to undergo clean thermal rearrangement to give isocoumarins 10 in high yields. This synthesis of isocoumarins, when applied to oxaindacenone 7, resulted in the total synthesis of coriandrin (1). (C) 2000 Elsevier Science Ltd. All rights reserved.
• Total Synthesis of Coriandrin
  作者：George A. Kraus、James Ridgeway

  DOI：10.1021/jo00096a013

  日期：1994.8

  Coriandrin, an antiviral agent, has been synthesized in nine steps from diketone 3. The key steps in the synthesis include an efficient aromatization reaction using N-bromosuccinimide and a palladium-mediated coupling of a benzylic bromide with a vinyl stannane.
• Mechanism-Based Inactivation of Hepatic Ethoxyresorufin O-Dealkylation Activity by Naturally Occurring Coumarins
  作者：Yingna Cai、Wanda Baer-Dubowska、Mike J. Ashwood-Smith、Oluna Ceska、Sanro Tachibana、John DiGiovanni

  DOI：10.1021/tx950208b

  日期：1996.1.1

  Several naturally occurring coumarins contained in the human diet have been found to be effective inhibitors and inactivators of murine hepatic ethoxyresorufin O-dealkylase (EROD) and pentoxyresorufin O-dealkylase in vitro [Cai, Y., Bennett, D., Nair, R. V., Ceska, O., Ashwood-Smith, M., and DiGiovanni, J. (1993) Chem. Res. Toxicol. 6, 872-879]. In the present study, these same coumarins decreased the content of: cytochrome P450 (P450) in either 3-methylcholanthrene (MC)- or phenobarbital-induced murine hepatic microsomes but did not have a major effect on heme content. Detailed in vitro studies with [C-14]coriandrin, which selectively inhibits and inactivates P450 1A1-mediated EROD activity, demonstrated that it covalently bound, in a preferential manner, to hepatic microsomal protein from MC-pretreated mice. A linear relationship was observed between covalent binding and loss of EROD activity. The inclusion of electrophile trapping agents in the incubations significantly inhibited the covalent binding of [C-14]coriandrin to microsomal protein. In addition, the covalent binding of [C-14]coriandrin was decreased 46% by 7,8-benzoflavone (7,8-BF), 58% by a monoclonal antibody with specificity toward MC-induced form(s) of P450, and 60% by ethoxyresorufin, implicating the bioactivation of coriandrin by P450 1A1. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [C-14]coriandrin-bound microsomal protein from MC-pretreated mice showed that [C-14]coriandrin bound covalently to a protein with an approximate molecular mass of 49 kDa. Again, addition of 7,8-BF or polyclonal antibody against P450 1A1 reduced the covalent binding of [C-14]coriandrin to this specific protein band. Interestingly, coriandrin was also found to be a potent inhibitor and inactivator of purified human P450 1A1. These results demonstrate that certain coumarins to which humans are exposed in the diet are bioactivated by P450 1A1 to reactive intermediates that subsequently form covalent adducts with the apoprotein, effectively destroying enzyme activity. Thus, certain naturally occurring coumarins may have a significant effect on human health.