ethyl 5,6-dihydroxy-2-methylbenzofuran-3-carboxylate | 83634-11-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: ethyl 5,6-dihydroxy-2-methylbenzofuran-3-carboxylate
• 英文别名: Ethyl 5,6-dihydroxy-2-methyl-1-benzofuran-3-carboxylate
• CAS: 83634-11-1
• 化学式: C₁₂H₁₂O₅
• 分子量: 236.224
• InChiKey: IOVWDJRWMXSWMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 5,6-dihydroxy-2-methylbenzofuran-3-carboxylate 在 咪唑 、 potassium fluoride 、 N-溴代丁二酰亚胺(NBS) 、 caesium carbonate 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 67.0h， 生成 allyl 5-((5-((5-((tert-butyldimethylsilyl)oxy)-3-(ethoxycarbonyl)-6-methoxybenzofuran-2-yl)methoxy)-3-(ethoxycarbonyl)-6-methoxybenzofuran-2-yl)methoxy)-6-methoxy-2-methylbenzofuran-3-carboxylate
  参考文献：
  名称：

  Designing Allosteric Regulators of Thrombin. Exosite 2 Features Multiple Subsites That Can Be Targeted by Sulfated Small Molecules for Inducing Inhibition

  摘要：

  We recently designed a group of novel exosite-2-directed sulfated, small, allosteric inhibitors of thrombin. To develop more potent inhibitors, monosulfated benzofuran tri- and tetrameric homologues of the parent designed dimers were synthesized in seven to eight steps and found to exhibit a wide range of potencies. Among these, trimer 9a was found to be nearly 10-fold more potent than the first generation molecules. Michaelis-Menten studies indicated an allosteric mechanism of inhibition. Competitive studies using a hirudin peptide (exosite 1 ligand) and unfractionated heparin, heparin octasaccharide, and gamma'-fibrinogen peptide (exosite 2 ligands) demonstrated exosite 2 recognition in a manner different from that of the parent dimers. Alanine scanning mutagenesis of 12 Arg/Lys residues of exosite 2 revealed a defect in 9a potency for Arg233Ala thrombin only confirming the major difference in site of recognition between the two structurally related sulfated benzofurans. The results suggest that multiple avenues are available within exosite 2 for inducing thrombin inhibition.

  DOI：

  10.1021/jm400369q
• 作为产物：
  描述：

  5-acetoxy-6-ethoxyoxalyloxy-2-methyl-benzofuran-3-carboxylic acid ethyl ester 在 盐酸 、 乙醇 作用下， 生成 ethyl 5,6-dihydroxy-2-methylbenzofuran-3-carboxylate 、 草酸二乙酯
  参考文献：
  名称：

  Bernatek; Thoresen, Acta Chemica Scandinavica (1947), 1959, vol. 13, p. 342

  摘要：

  DOI：

文献信息

• Benzofuran-Based Estrogen Receptor α Modulators as Anti-Cancer Therapeutics: In Silico and Experimental Studies
  作者：Min Leow、Hui Li Chin、Peggy Yu、Kalyan Pasunooti、Raymond Xu Tay、Dawei Zhang、Ho Yoon、Xue-Wei Liu

  DOI：10.2174/0929867311320220007

  日期：2013.6.1

  In the search for new estrogen receptor alpha (ERα) modulators, a trial molecular screening was conducted and 5,6-dihydroxybenzofuran was identified as a possible drug target for ERα. The target molecular modelling molecule 1 and a series of 5,6-dihydroxybenzofurans have been synthesized and evaluated for their anti-proliferation activities against MCF-7 and MDA-MB-231 cells. From the SAR studies, potential functional groups have been identified, the two hydroxyl groups at C-5 and C-6 and the phenyl ring at C-2, which showed considerable cytotoxicity in MCF-7 breast cancer cells. In addition, the apoptotic abilities of the compounds have been measured in both MCF-7 ER(+) and MDA-MB-231 ER(-) breast cancer cells. The results demonstrated that our compounds inhibit MCF-7 breast cancer cells via ER(+). These preliminary results provide valuable information towards the identification of important functional groups present on 5,6-dihydroxybenzofuran, which could be a promising scaffold for designing novel ER ligands.

  在寻找新的雌激素受体α（ERα）调节剂的过程中，进行了一次分子筛选试验，并确定5,6-二羟基苯并呋喃作为可能的ERα药物作用靶点。针对该目标分子模型，合成了一系列5,6-二羟基苯并呋喃分子，并评估了它们对MCF-7和MDA-MB-231细胞的抗增殖活性。通过结构-活性关系（SAR）研究，鉴定出潜在功能团，即C-5和C-6位置上的两个羟基以及C-2位置的苯环，这些功能团在MCF-7乳腺癌细胞中显示出显著的细胞毒性。此外，该系列化合物在MCF-7 ER(+)和MDA-MB-231 ER(-)乳腺癌细胞中的凋亡能力也得到了测定。结果表明，我们的化合物通过ER(+)途径抑制了MCF-7乳腺癌细胞。这些初步结果为鉴定5,6-二羟基苯并呋喃上的重要功能团提供了宝贵信息，该分子骨架可能成为设计新型ER配体的有前景的支架。
• Cocatalytic Enzyme System for the Michael Addition Reaction of in-situ-Generated<i>ortho</i>-Quinones
  作者：Suteera Witayakran、Arthur J. Ragauskas

  DOI：10.1002/ejoc.200800791

  日期：2009.1

  A laccase-lipase cocatalytic system was used to catalyze the domino reaction between catechols and nucleophilic reagents including 1,3-dicarbonyl compounds and aromatic amines in aqueous medium at room temperature. Lipase acted as a catalyst for Michael addition step, and also enhanced the overall yield of the final products. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

  漆酶-脂肪酶共催化系统用于在室温下在水性介质中催化儿茶酚与亲核试剂（包括 1,3-二羰基化合物和芳香胺）之间的多米诺骨牌反应。脂肪酶作为迈克尔加成步骤的催化剂，也提高了最终产品的总产率。((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
• One-pot synthesis of 5,6-dihydroxylated benzo[b]furan derivatives
  作者：Li-Xia Pei、Yue-Ming Li、Xian-Zhang Bu、Lian-Quan Gu、Albert S.C. Chan

  DOI：10.1016/j.tetlet.2006.02.055

  日期：2006.4

  presence of sodium iodate and pyridine, several 5,6-dihydroxylated benzo[b]furan derivatives were synthesized via oxidation–Michael addition of β-dicarbonyl compounds with catechols in a one-pot procedure. The final products were confirmed by ESMS, NMR, and single-crystal X-ray diffraction study. The mechanism different from that of electrochemical methods was proposed based on DFT calculation.

  在碘酸钠和吡啶存在下，通过一锅法将β-二羰基化合物与邻苯二酚进行氧化-迈克尔加成反应，合成了5,6-二羟基化的苯并[ b ]呋喃衍生物。最终产物通过ESMS，NMR和单晶X射线衍射研究确认。基于DFT计算，提出了不同于电化学方法的机理。
• Electrochemical oxidation of catechols in the presence of ethyl-2-chloroacetoacetate. Synthesis and mechanistic study
  作者：Mojtaba Shamsipur、Saied Saeed Hosseiny Davarani、Davood Nematollahi

  DOI：10.1002/jhet.5570430638

  日期：2006.11

  Electrochemical oxidation of catechol and some of 3-substituted catechols (1a-c) has been studied in the presence of ethyl-2-chloroacetoacetate (3) in water/acetonitrile (90:10) solution using cyclic voltammetry and controlled-potential coulometry. The results indicate that the quinones derived from catechols (1a-c) participate in Michael addition reactions with ethyl-2-chloroacetoacetate(3), with

  使用循环伏安法和可控电库仑法在水/乙腈（90:10）溶液中存在2-氯乙酰乙酸乙酯（3）的情况下，研究了邻苯二酚和一些3-取代的邻苯二酚（1a-c）的电化学氧化。结果表明，衍生自邻苯二酚（1a-c）的醌与-2-氯乙酰乙酸乙酯（3）参与迈克尔加成反应，每1分子仅消耗两个电子，形成相应的苯并呋喃（10a-c）。 。苯并呋喃的电化学合成（10a-c）已成功地在碳棒电极和未分割的电解槽中进行，具有良好的产率和纯度。提出了一种新的电极双电子机理。
• First steps in the direction of synthetic, allosteric, direct inhibitors of thrombin and factor Xa
  作者：Jenson Verghese、Aiye Liang、Preet Pal Singh Sidhu、Michael Hindle、Qibing Zhou、Umesh R. Desai

  DOI：10.1016/j.bmcl.2009.06.013

  日期：2009.8

  Designing non-saccharide functional mimics of heparin is a major challenge. In this work, a library of small, aromatic molecules based on the sulfated DHP scaffold was synthesized and screened against thrombin and factor Xa. The results reveal that (i) selected monomeric benzofuran derivatives inhibit the two enzymes, albeit weakly; (ii) the two enzymes recognize different structural features in the

  设计肝素的非糖类功能模拟物是一项重大挑战。在这项工作中，合成了一个基于硫酸化 DHP 支架的芳香小分子库，并针对凝血酶和 Xa 因子进行了筛选。结果表明：（ⅰ）选择的单体苯并呋喃衍生物抑制这两种酶，尽管弱; (ii) 这两种酶识别所研究的苯并呋喃中的不同结构特征，表明识别具有显着的选择性；(iii) 抑制机制是变构的。这些分子代表了两种酶的第一个变构小分子抑制剂。