2'',4'',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'',4'',4'-trimethoxy-2'-hydroxychalcone
• 英文别名: 2'-hydroxy-2,4,4'-trimethoxychalcone；2'-hydroxy-4,4',6-trimethoxychalcone；2'-Hydroxy-4,6,4'-trimethoxychalcone；3-(2,4-dimethoxyphenyl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one
• 化学式: C₁₈H₁₈O₅
• 分子量: 314.338
• InChiKey: ZTIPWOFLPVWZDX-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'',4'',4'-trimethoxy-2'-hydroxychalcone 在 碘 作用下， 以 二甲基亚砜 为溶剂， 反应 0.33h， 以80%的产率得到2-(2,4-dimethoxyphenyl)-7-methoxy-4H-chromen-4-one
  参考文献：
  名称：

  作为有效的组织蛋白酶V抑制剂的Chalcones和Flavones组合文库的溶液相合成

  摘要：

  组织蛋白酶V是一种木瓜蛋白酶样半胱氨酸蛋白酶。它参与人类T细胞的控制（负责细胞免疫），并在蛋白水解酶中表现出最大的弹性。因此，组织蛋白酶V是治疗动脉粥样硬化的潜在分子靶标。在目前的工作中，针对组织蛋白酶V筛选了天然类黄酮，并确定了两种黄酮是组织蛋白酶V的有效抑制剂。基于此结果，在溶液相中使用清道夫试剂制备了查尔酮和黄酮的组合文库，并经过充分评估。

  DOI：

  10.1021/cc100076k
• 作为产物：
  描述：

  2,4-二羟基苯乙酮 在 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 36.0h， 生成 2'',4'',4'-trimethoxy-2'-hydroxychalcone
  参考文献：
  名称：

  （±）-桑巴糖醇五甲基醚仿生合成的策略

  摘要：

  摘要 描述了仿生合成morusalbanol A五甲基醚的策略。合成基于脱氢异戊二烯基二烯和查尔酮二烯亲核体之间的氢键辅助的Diels-Alder环加成反应。选择性裂解生成的环加合物的邻甲基醚可旋转C3-C21键，随后进行分子内环化，可得到（±）-morusalbanol A的五甲基醚。与天然产物morusalbanol A一样，还有许多关键质子标题产物的NMR谱中没有碳信号。 描述了仿生合成morusalbanol A五甲基醚的策略。合成基于脱氢异戊二烯基二烯和查尔酮二烯亲核体之间的氢键辅助的Diels-Alder环加成反应。选择性裂解生成的环加合物的邻甲基醚可旋转C3-C21键，随后进行分子内环化，可得到（±）-morusalbanol A的五甲基醚。与天然产物morusalbanol A一样，还有许多关键质子标题产物的NMR谱中没有碳信号。

  DOI：

  10.1055/s-0035-1560434

文献信息

• Mulberry Diels−Alder Adducts: Synthesis of Chalcomoracin and Mulberrofuran C Methyl Ethers
  作者：Christian Gunawan、Mark A. Rizzacasa

  DOI：10.1021/ol9026705

  日期：2010.4.2

  heptamethyl ethers of the mulberry Diels−Alder adducts chalcomoracin (1) and mulberrofuran J (2) is described. The key steps in each approach involved a biomimetic intermolecular [4+2]-cycloaddition between a dehydroprenylphenol diene derived from an isoprenoid-substituted phenolic compound and an α,β-unsaturated alkene of a chalcone as the dienophile. Critical to the success of the Diels−Alder reaction

  描述了桑树Diels-Alder加合物查库拉霉素（1）和桑fur呋喃J（2）的每种七甲基醚的合成。每种方法的关键步骤都涉及到由异戊二烯基取代的酚类化合物衍生的脱氢异戊二烯基苯酚二烯与查耳酮的α，β-不饱和烯烃作为亲二烯体之间的仿生分子间[4 + 2]-环加成反应。Diels-Alder反应成功的关键是2'-羟基查耳酮中存在游离酚。
• 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。
• 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.