(2R,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxychroman-3-yl cyclopropanecarboxylate | 1608504-22-8

• 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: (2R,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxychroman-3-yl cyclopropanecarboxylate
• 英文别名: [(2R,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl] cyclopropanecarboxylate
• CAS: 1608504-22-8
• 化学式: C₁₉H₁₈O₇
• 分子量: 358.348
• InChiKey: QWEKUNCFHMHMCR-QZTJIDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  儿茶提取物 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 L-Selectride 、 potassium carbonate 、 戴斯-马丁氧化剂 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -78.0~20.0 ℃ 、206.85 kPa 条件下， 生成 (2R,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxychroman-3-yl cyclopropanecarboxylate
  参考文献：
  名称：

  Towards the discovery of drug-like epigallocatechin gallate analogs as Hsp90 inhibitors

  摘要：

  (-)-表没食子儿茶素没食子酸酯(EGCG)是绿茶的主要黄酮类化合物,已被广泛研究用于多种生物活性,包括抗感染、抗炎、抗癌和神经营养。现有的EGCG结构活性数据主要局限于对简单醚和羟基缺失的探索。由于多个酚羟基和代谢不稳定的酯,EGCG的药物样性质较差。 本研究通过探索一系列半合成和合成的衍生物,显著扩展了结构活性的理解。这些衍生物具有酯替换和各种取代的芳香族和脂环族基团,包含更多的药物样取代基。获得这些分子的Hsp90抑制结构活性关系。 结果表明，酰胺和磺酰胺连接物是适合的酯替换。羟基化的芳香环和EGCG中的顺式立体化学并非Hsp90抑制所必需。系列中的选定类似物在Hsp90活性的荧光素酶重折叠测定中比EGCG更有效。© 2014 Elsevier Ltd. 保留所有权利。

  DOI：

  10.1016/j.bmcl.2014.03.088

文献信息

• Ebola Entry Inhibitors Discovered from Maesa perlarius
  作者：Nga Yi Tsang、Wan-Fei Li、Elizabeth Varhegyi、Lijun Rong、Hong-Jie Zhang

  DOI：10.3390/ijms23052620

  日期：——

  Ebola virus disease (EVD), a disease caused by infection with Ebola virus (EBOV), is characterized by hemorrhagic fever and a high case fatality rate. With limited options for the treatment of EVD, anti-Ebola viral therapeutics need to be urgently developed. In this study, over 500 extracts of medicinal plants collected in the Lingnan region were tested against infection with Ebola-virus-pseudotyped particles (EBOVpp), leading to the discovery of Maesa perlarius as an anti-EBOV plant lead. The methanol extract (MPBE) of the stems of this plant showed an inhibitory effect against EBOVpp, with an IC50 value of 0.52 µg/mL, which was confirmed by testing the extract against infectious EBOV in a biosafety level 4 laboratory. The bioassay-guided fractionation of MPBE resulted in three proanthocyanidins (procyanidin B2 (1), procyanidin C1 (2), and epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin (3)), along with two flavan-3-ols ((+)-catechin (4) and (−)-epicatechin (5)). The IC50 values of the compounds against pseudovirion-bearing EBOV-GP ranged from 0.83 to 36.0 µM, with 1 as the most potent inhibitor. The anti-EBOV activities of five synthetic derivatives together with six commercially available analogues, including EGCG ((−)-epigallocatechin-3-O-gallate (8)), were further investigated. Molecular docking analysis and binding affinity measurement suggested the EBOV glycoprotein could be a potential molecular target for 1 and its related compounds.

  埃博拉病毒病（EVD）是由埃博拉病毒（EBOV）感染引起的疾病，其特征是出血热和高病例死亡率。由于治疗EVD的选择有限，迫切需要开发抗埃博拉病毒治疗方法。在这项研究中，对岭南地区收集的500多种药用植物提取物进行了针对埃博拉病毒假性颗粒（EBOVpp）感染的测试，发现了马氏珠花作为抗埃博拉病毒植物的先导物质。该植物茎部的甲醇提取物（MPBE）对EBOVpp表现出抑制作用，IC50值为0.52 µg/mL，通过在生物安全级别4实验室中对提取物进行感染性EBOV测试进行确认。MPBE的生物分馏结果为三种原花青素（原花青素B2（1），原花青素C1（2）和表儿茶素-（4β→8）-表儿茶素-（4β→8）-表儿茶素-（4β→8）-表儿茶素（3）），以及两种黄烷-3-醇（（+）-儿茶素（4）和（-）-表儿茶素（5））。这些化合物对携带EBOV-GP的假病毒的IC50值范围从0.83到36.0 µM不等，其中1是最有效的抑制剂。进一步研究了五种合成衍生物以及包括EGCG（（-）-表儿茶素-3-O-没食子酸酯（8））在内的六种商业可得的类似物的抗埃博拉病毒活性。分子对接分析和结合亲和力测定表明，EBOV糖蛋白可能是1及其相关化合物的潜在分子靶点。
• Towards the discovery of drug-like epigallocatechin gallate analogs as Hsp90 inhibitors
  作者：Rohit Bhat、Amna T. Adam、Jungeun Jasmine Lee、Thomas A. Gasiewicz、Ellen C. Henry、David P. Rotella

  DOI：10.1016/j.bmcl.2014.03.088

  日期：2014.5

  ( - )-Epigallocatechin gallate (EGCG) is the major flavonoid of green tea and has been widely explored for a range of biological activities including anti- infective, anti-inflammatory, anti-cancer, and neuroprotection. Existing structure-activity data for EGCG has been largely limited to exploration of simple ethers and hydroxyl deletion. EGCG has poor drug-like properties because of multiple phenolic hydroxyl moieties and a metabolically labile ester. This work reports a substantial expansion of structure-activity understanding by exploring a range of semi-synthetic and synthetic derivatives with ester replacements and variously substituted aromatic and alicyclic groups containing more drug-like substituents. Structure-activity relationships for these molecules were obtained for Hsp90 inhibition. The results indicate that amide and sulfonamide linkers are suitable ester replacements. Hydroxylated aromatic rings and the cis- stereochemistry in EGCG are not essential for Hsp90 inhibition. Selected analogs in this series are more potent than EGCG in a luciferase refolding assay for Hsp90 activity. (C) 2014 Elsevier Ltd. All rights reserved.

  (-)-表没食子儿茶素没食子酸酯(EGCG)是绿茶的主要黄酮类化合物,已被广泛研究用于多种生物活性,包括抗感染、抗炎、抗癌和神经营养。现有的EGCG结构活性数据主要局限于对简单醚和羟基缺失的探索。由于多个酚羟基和代谢不稳定的酯,EGCG的药物样性质较差。 本研究通过探索一系列半合成和合成的衍生物,显著扩展了结构活性的理解。这些衍生物具有酯替换和各种取代的芳香族和脂环族基团,包含更多的药物样取代基。获得这些分子的Hsp90抑制结构活性关系。 结果表明，酰胺和磺酰胺连接物是适合的酯替换。羟基化的芳香环和EGCG中的顺式立体化学并非Hsp90抑制所必需。系列中的选定类似物在Hsp90活性的荧光素酶重折叠测定中比EGCG更有效。© 2014 Elsevier Ltd. 保留所有权利。