2'',3'',4'-trimethoxy-2'-hydroxychalcone

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 2'',3'',4'-trimethoxy-2'-hydroxychalcone
• 英文别名: 2,3,4'-trimethoxy-2'-hydroxy-chalcone；2'-hydroxy-4',5,6-trimethoxychalcone；3-(2,3-Dimethoxyphenyl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one
• 化学式: C₁₈H₁₈O₅
• 分子量: 314.338
• InChiKey: ZPBDKGAFNCLNTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2'',3'',4'-trimethoxy-2'-hydroxychalcone 在 Aspergillus niger LSPN₀₀₁ 作用下， 以 乙醇 为溶剂， 反应 120.0h， 以19%的产率得到4',2''-dimethoxy-2',3''-dihydroxychalcone
  参考文献：
  名称：

  Aspergillus niger catalyzes the synthesis of flavonoids from chalcones

  摘要：

  Flavonoids, which have many biological activities and have been widely used in nature, can be artificially synthesized. However, regioselective cyclization of chalcones is difficult by chemical methods. In this study, we demonstrated that Aspergillus niger is capable of cyclizing chalcones to flavanones, affording a mimic of plant biosynthetic processes. Chalcones 1-6 were biotransformated to the modified chalcones 8-14 and to the flavanones 15-27. The biotransformation showed that enzymatic cyclization and demethylation occurred during the first days of biotransformation; in contrast, hydroxylation is a later process. With a longer culturing time, it is possible to obtain more hydroxylated flavanones with excellent yields.

  DOI：

  10.3109/10242422.2013.813489
• 作为产物：
  描述：

  丹皮酚 、 2,3-二甲氧基苯甲醛 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 2'',3'',4'-trimethoxy-2'-hydroxychalcone
  参考文献：
  名称：

  2'-羟基查耳酮中相关的实验电化学和理论计算：分子内氢键的作用†

  摘要：

  在这项工作中，我们提出了一系列抗甲氧基化2'-羟基查耳酮的分子结构和电化学行为的研究，其抗肿瘤活性已在前面进行了描述。循环伏安法用于定量表征阴离子自由基的形成和稳定性。通过密度泛函理论（DFT）计算研究了中性化合物及其阴离子自由基的分子结构，特别是分子内氢键（IHB）。相对于中性物种，检查了阴离子的几何和边界轨道变化，并计算了绝热和垂直电子亲和力（AEA，VEA）以及垂直脱离能（VDE）。1 H-NMR化学位移。发现在环A和B上的取代方式，IHB的强度和还原电位之间存在直接关系。NBO能量（ ΔE （2）ij）表明，对IHBs稳定的主要贡献来自LP→σ*相互作用。由ΔE （2）ij给出的IHBs强度与实验还原电位具有显着的定量相关性，至少就我们所知，对于任何类型的分子，以前都没有描述过。结果表明，甲氧基取代模式对这些化合物的IHB和氧化还原特性的重要性。我们的发现对抗肿瘤查耳酮的设计具有潜在的影响。

  DOI：

  10.1039/c5ra10140a

文献信息

• Investigation of Chalcones as Selective Inhibitors of the Breast Cancer Resistance Protein: Critical Role of Methoxylation in both Inhibition Potency and Cytotoxicity
  作者：Glaucio Valdameri、Charlotte Gauthier、Raphaël Terreux、Rémy Kachadourian、Brian J. Day、Sheila M. B. Winnischofer、Maria E. M. Rocha、Véronique Frachet、Xavier Ronot、Attilio Di Pietro、Ahcène Boumendjel

  DOI：10.1021/jm2016528

  日期：2012.4.12

  ABCG2 plays a major role in anticancer-drug efflux and related tumor multidrug resistance. Potent and selective ABCG2 inhibitors with low cytotoxicity were investigated among a series of 44 chalcones and analogues (1,3-diarylpropenones), by evaluating their inhibitory effect on the transport of mitoxantrone, a known ABCG2 substrate. Six compounds producing complete inhibition with IC50 values below 0.5 mu M and high selectivity for ABCG2 were identified. The number and position of methoxy substituents appeared to be critical for both inhibition and cytotoxicity. The best compounds, with potent inhibition and low toxicity, contained an N-methyl-1-indolyl (compound 38) or a 6'-hydroxyl-2',4'-dimethoxy-1-phenyl (compound 27) moiety (A-ring) and two methoxy groups at positions 2 and 6 of the 3-phenyl moiety (B-ring). Methoxy substitution contributed to inhibition at positions 3 and 5, but had a negative effect at position 4. Finally, methoxy groups at positions 3, 4, and 5 of the B-ring markedly increased cytotoxicity and, therefore, should be avoided.
• A Synthetic Chalcone as a Potent Inducer of Glutathione Biosynthesis
  作者：Remy Kachadourian、Brian J. Day、Subbiah Pugazhenti、Christopher C. Franklin、Estelle Genoux-Bastide、Gregory Mahaffey、Charlotte Gauthier、Attilio Di Pietro、Ahcène Boumendjel

  DOI：10.1021/jm2016073

  日期：2012.2.9

  Chalcones continue to attract considerable interest due to their anti-inflammatory and antiangiogenic properties. We recently reported the ability of 2',5'-dihydroxychalcone (2',5'-DHC) to induce both breast cancer resistance protein-mediated export of glutathione (GSH) and c-Jun N-terminal kinase-mediated increased intracellular GSH levels. Herein, we report a structure-activity relationship study of a series of 30 synthetic chalcone derivatives with hydroxyl, methoxyl, and halogen (F andCl) substituents and their ability to increase intracellular GSH levels. This effect was drastically improved with one or two electrowithdrawing groups on phenyl ring B and up to three methoxyl and/or hydroxyl groups on phenyl ring A. The optimal structure, 2-chloro-4',6'-dimethoxy-2'-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements.
• Aspergillus niger catalyzes the synthesis of flavonoids from chalcones
  作者：Julio Alarcón、Joel Alderete、Carlos Escobar、Ramiro Araya、Carlos L. Cespedes

  DOI：10.3109/10242422.2013.813489

  日期：2013.8

  Flavonoids, which have many biological activities and have been widely used in nature, can be artificially synthesized. However, regioselective cyclization of chalcones is difficult by chemical methods. In this study, we demonstrated that Aspergillus niger is capable of cyclizing chalcones to flavanones, affording a mimic of plant biosynthetic processes. Chalcones 1-6 were biotransformated to the modified chalcones 8-14 and to the flavanones 15-27. The biotransformation showed that enzymatic cyclization and demethylation occurred during the first days of biotransformation; in contrast, hydroxylation is a later process. With a longer culturing time, it is possible to obtain more hydroxylated flavanones with excellent yields.
• Correlating experimental electrochemistry and theoretical calculations in 2′-hydroxy chalcones: the role of the intramolecular hydrogen bond
  作者：Maximiliano Martínez-Cifuentes、Ricardo Salazar、Carlos A. Escobar、Boris E. Weiss-López、Leonardo S. Santos、Ramiro Araya-Maturana

  DOI：10.1039/c5ra10140a

  日期：——

  on the molecular structure and electrochemical behavior of a series of methoxylated 2′-hydroxychalcones, whose antitumor activity has been previously described. Cyclic voltammetry was used to quantitatively characterize the formation and stability of the anion radicals. The molecular structure of the neutral compounds and their anion radicals, particularly the intramolecular hydrogen bonds (IHB), were

  在这项工作中，我们提出了一系列抗甲氧基化2'-羟基查耳酮的分子结构和电化学行为的研究，其抗肿瘤活性已在前面进行了描述。循环伏安法用于定量表征阴离子自由基的形成和稳定性。通过密度泛函理论（DFT）计算研究了中性化合物及其阴离子自由基的分子结构，特别是分子内氢键（IHB）。相对于中性物种，检查了阴离子的几何和边界轨道变化，并计算了绝热和垂直电子亲和力（AEA，VEA）以及垂直脱离能（VDE）。1 H-NMR化学位移。发现在环A和B上的取代方式，IHB的强度和还原电位之间存在直接关系。NBO能量（ ΔE （2）ij）表明，对IHBs稳定的主要贡献来自LP→σ*相互作用。由ΔE （2）ij给出的IHBs强度与实验还原电位具有显着的定量相关性，至少就我们所知，对于任何类型的分子，以前都没有描述过。结果表明，甲氧基取代模式对这些化合物的IHB和氧化还原特性的重要性。我们的发现对抗肿瘤查耳酮的设计具有潜在的影响。