4’-羟基-3,3’,5-三甲氧基二苯乙烯 | 108957-72-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 4’-羟基-3,3’,5-三甲氧基二苯乙烯
• 中文别名: 4'-羟基-3,3',5-三甲氧基二苯乙烯
• 英文名称: (E)-4-(3,5-dimethoxystyryl)-2-methoxyphenol
• 英文别名: 4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]-2-methoxyphenol
• CAS: 108957-72-8
• 化学式: C₁₇H₁₈O₄
• 分子量: 286.328
• InChiKey: QEHTYBCDRGQJGN-SNAWJCMRSA-N

物化性质

• 熔点：
  82-84 °C
• 沸点：
  446.7±40.0 °C(Predicted)
• 密度：
  1.177±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2909500000

反应信息

• 作为反应物：
  描述：

  4’-羟基-3,3’,5-三甲氧基二苯乙烯 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以62%的产率得到白皮杉醇
  参考文献：
  名称：

  Piceatannol和生物活性二苯乙烯衍生物对缺氧诱导的H9c2心肌毒性和作为5-LOX抑制剂的结构阐明的保护作用。

  摘要：

  具有众所周知的抗氧化和抗自由基性能的丁二烯在包括心血管疾病在内的不同病理中均有益。进行本研究以研究白藜芦醇（1）和美​​沙酮（2）对H9c2心肌细胞系中低氧诱导的氧化应激的潜在保护作用及其潜在机制。化合物1和2在无微摩尔浓度或亚微摩尔浓度下均显着抑制过氧亚硝酸盐和硫代巴比妥酸水平的释放，这种作用在皮卡季醇处理的细胞中更为明显，以浓度依赖的方式显着增加了MnSOD蛋白水平。此外，由于天然资源中苦味甘苦的苦味酚醇比母体化合物具有更高的生物活性，我们特此报告聚焦二苯乙烯化合物库的非常快速的合成和基于结构的详细设计。最后，考虑到缺氧诱导的ROS积累也随着白三烯的产生而增加了5-脂氧合酶（5-LOX）的表达和活性，我们已经揭示了对5-LOX活性至关重要的结构关键因素。在合成的类似物（3-7）中，化合物7在改善心肌细胞活力和抑制5-LOX方面最有效。总之，建模和实验研究为进一步优化二苯乙烯类似物作为炎

  DOI：

  10.1016/j.ejmech.2019.07.033
• 作为产物：
  描述：

  trans-3,3',5-trimethoxy-4'-tert-butyldimethylsilyloxystilbene 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.75h， 以88%的产率得到4’-羟基-3,3’,5-三甲氧基二苯乙烯
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Resveratrol and Analogues as Apoptosis-Inducing Agents

  摘要：

  Resveratrol 1 (3,4',5-trihydroxy-trans-stilbene), a phytoalexin present in grapes and other food products, has recently been suggested as a potential cancer chemopreventive agent based on its striking inhibitory effects on cellular events associated with cancer initiation, promotion, and progression. This triphenolic stilbene has also displayed in vitro growth inhibition in a number of human cancer cell lines. In this context, a series of cis- and trans-stilbene-based resveratrols were prepared with the aim of discovering new lead compounds with clinical potential. All the synthesized compounds were tested in vitro for cell growth inhibition and the ability to induce apoptosis in HL60 promyelocytic leukemia cells. The tested trans-stilbene derivatives were less potent than their corresponding cis isomers, except for trans-resveratrol, whose cis isomer was less active. The best results were obtained with compounds 11b and 7b, the cis-3,5-dimethoxy derivatives of rhapontigenin 10a (3,5,3'-trihydroxy-4'methoxy-trans-stilbene) and its 3'-amino derivative 10b, respectively, which showed apoptotic activity at nanomolar concentrations. The corresponding trans isomers 12b and 8b were less active both as antiproliferative and as apoptosis-inducing agents. Of interest, 11b and 7b were active toward resistant HL60R cells and their activity was higher than that of several classic chemotherapeutic agents. The flow cytometry assay showed that at 50 nM compounds 7b or 11b were able to recruit almost all cells in the apoptotic sub-G(0)-G(1) peek, thus suggesting that the main mechanism of cytotoxicity of these compounds could be the activation of apoptosis. These data indicate unambiguously that structural alteration of the stilbene motif of resveratrol can be extremely effective in producing potent apoptosis-inducing agents.

  DOI：

  10.1021/jm030785u

文献信息

• Syntheses of Resveratrol and its Hydroxylated Derivatives as Radical Scavenger and Tyrosinase Inhibitor
  作者：Hyun-Suck Lee、Byung-Won Lee、Mi-Ran Kim、Jong-Gab Jun

  DOI：10.5012/bkcs.2010.31.04.971

  日期：2010.4.20

  Eight hydroxylated stilbene derivatives including resveratrol, desoxyrhapontigenin and piceatannol as potential radical scavenger and tyrosinase inhibitor are synthesized using optimized Wittig-Horner reaction for excellent trans-selectivity in good yields. Antioxidant activity was tested against ABTS radical and tyrosinase inhibitory activity was performed with L-tyrosine as the substrate based on previous procedure with some modification. In general, catecholic stilbenes showed stronger activity against ABTS radical and resorcinolic moiety showed stronger tyrosinase inhibitory activity. Synthetic piceatannol which containing both catecholic and resorcinolic moieties showed the strongest activity in both as ABTS radical scavenger and tyrosinase inhibitor with $IC_50}$ values of 4.1 and $8.6\;\mu}M$, respectively.

  通过优化的Wittig-Horner反应合成了八种含羟基的二苯乙烯衍生物，包括白藜芦醇、去氧大黄素和松柏苷，这些化合物具有潜在的自由基清除和酪氨酸酶抑制作用，并表现出优异的反式选择性，产率良好。抗氧化活性针对ABTS自由基进行了测试，酪氨酸酶抑制活性则以L-酪氨酸为底物，参考先前的方法并进行了一些修改。总体而言，含儿茶酚基团的二苯乙烯对ABTS自由基显示出更强的活性，而含间苯二酚基团的化合物则表现出更强的酪氨酸酶抑制活性。合成的松柏苷同时含有儿茶酚和间苯二酚基团，在ABTS自由基清除和酪氨酸酶抑制方面显示出最强的活性，其$IC_50}$值分别为4.1和$8.6\;\mu}M$。
• Kashiwada, Yoshiki; Nonaka, Gen-Ichiro; Nishioka, Itsuo, Chemical and pharmaceutical bulletin, 1988, vol. 36, p. 1545 - 1549
  作者：Kashiwada, Yoshiki、Nonaka, Gen-Ichiro、Nishioka, Itsuo、Nishizawa, Makoto、Yamagishi, Takashi

  DOI：——

  日期：——
• GILL, M. T.;BAJAJ, R.;CHANG, C. J.;NICHOLS, D. E.;MCLAUGHLIN, J. L., J. MATUR. PROD., 50,(1987) N 1, 36-40
  作者：GILL, M. T.、BAJAJ, R.、CHANG, C. J.、NICHOLS, D. E.、MCLAUGHLIN, J. L.

  DOI：——

  日期：——
• Protective effect of piceatannol and bioactive stilbene derivatives against hypoxia-induced toxicity in H9c2 cardiomyocytes and structural elucidation as 5-LOX inhibitors
  作者：Mariarosaria Boccellino、Maria Donniacuo、Ferdinando Bruno、Barbara Rinaldi、Lucio Quagliuolo、Marika Ambruosi、Simona Pace、Mario De Rosa、Abdurrahman Olgaç、Erden Banoglu、Nicola Alessio、Antonio Massa、Haroon Kahn、Oliver Werz、Antonio Fiorentino、Rosanna Filosa

  DOI：10.1016/j.ejmech.2019.07.033

  日期：2019.10

  Stilbenes with well-known antioxidant and antiradical properties are beneficial in different pathologies including cardiovascular diseases. The present research was performed to investigate the potential protective effect of resveratrol (1) and piceatannol (2), against hypoxia-induced oxidative stress in the H9c2 cardiomyoblast cell line, and the underlying mechanisms. Compounds 1 and 2 significantly

  具有众所周知的抗氧化和抗自由基性能的丁二烯在包括心血管疾病在内的不同病理中均有益。进行本研究以研究白藜芦醇（1）和美​​沙酮（2）对H9c2心肌细胞系中低氧诱导的氧化应激的潜在保护作用及其潜在机制。化合物1和2在无微摩尔浓度或亚微摩尔浓度下均显着抑制过氧亚硝酸盐和硫代巴比妥酸水平的释放，这种作用在皮卡季醇处理的细胞中更为明显，以浓度依赖的方式显着增加了MnSOD蛋白水平。此外，由于天然资源中苦味甘苦的苦味酚醇比母体化合物具有更高的生物活性，我们特此报告聚焦二苯乙烯化合物库的非常快速的合成和基于结构的详细设计。最后，考虑到缺氧诱导的ROS积累也随着白三烯的产生而增加了5-脂氧合酶（5-LOX）的表达和活性，我们已经揭示了对5-LOX活性至关重要的结构关键因素。在合成的类似物（3-7）中，化合物7在改善心肌细胞活力和抑制5-LOX方面最有效。总之，建模和实验研究为进一步优化二苯乙烯类似物作为炎
• Synthesis and Biological Evaluation of Resveratrol and Analogues as Apoptosis-Inducing Agents
  作者：Marinella Roberti、Daniela Pizzirani、Daniele Simoni、Riccardo Rondanin、Riccardo Baruchello、Caterina Bonora、Filippo Buscemi、Stefania Grimaudo、Manlio Tolomeo

  DOI：10.1021/jm030785u

  日期：2003.7.1

  Resveratrol 1 (3,4',5-trihydroxy-trans-stilbene), a phytoalexin present in grapes and other food products, has recently been suggested as a potential cancer chemopreventive agent based on its striking inhibitory effects on cellular events associated with cancer initiation, promotion, and progression. This triphenolic stilbene has also displayed in vitro growth inhibition in a number of human cancer cell lines. In this context, a series of cis- and trans-stilbene-based resveratrols were prepared with the aim of discovering new lead compounds with clinical potential. All the synthesized compounds were tested in vitro for cell growth inhibition and the ability to induce apoptosis in HL60 promyelocytic leukemia cells. The tested trans-stilbene derivatives were less potent than their corresponding cis isomers, except for trans-resveratrol, whose cis isomer was less active. The best results were obtained with compounds 11b and 7b, the cis-3,5-dimethoxy derivatives of rhapontigenin 10a (3,5,3'-trihydroxy-4'methoxy-trans-stilbene) and its 3'-amino derivative 10b, respectively, which showed apoptotic activity at nanomolar concentrations. The corresponding trans isomers 12b and 8b were less active both as antiproliferative and as apoptosis-inducing agents. Of interest, 11b and 7b were active toward resistant HL60R cells and their activity was higher than that of several classic chemotherapeutic agents. The flow cytometry assay showed that at 50 nM compounds 7b or 11b were able to recruit almost all cells in the apoptotic sub-G(0)-G(1) peek, thus suggesting that the main mechanism of cytotoxicity of these compounds could be the activation of apoptosis. These data indicate unambiguously that structural alteration of the stilbene motif of resveratrol can be extremely effective in producing potent apoptosis-inducing agents.