(E)-1-<4-<(tert-butyldimethylsilyl)oxy>phenyl>-2-(3,4,5-trimethoxyphenyl)ethene | 134029-67-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (E)-1-<4-<(tert-butyldimethylsilyl)oxy>phenyl>-2-(3,4,5-trimethoxyphenyl)ethene
• 英文别名: (E)-(tert-Butyldimethylsilyl)-4-<2-(3',4',5'-trimethoxyphenyl)ethenyl>phenol；(E)-1-[(4-t-Butyldimethylsilyloxy)phenyl]-2-(3,4,5-trimethoxyphenyl)ethene；(E)-1-{4-[(tert-butyldimethylsilyl)oxy]phenyl}-2-(3,4,5-trimethoxyphenyl)ethene；tert-butyl-dimethyl-[4-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenoxy]silane
• CAS: 134029-67-7
• 化学式: C₂₃H₃₂O₄Si
• 分子量: 400.59
• InChiKey: VHVFBVPDUHTLSL-MDZDMXLPSA-N

物化性质

• 沸点：
  465.3±45.0 °C(Predicted)
• 密度：
  1.035±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.27
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-1-<4-<(tert-butyldimethylsilyl)oxy>phenyl>-2-(3,4,5-trimethoxyphenyl)ethene 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以62 %的产率得到(E)-4’-羟基-3,4,5-三甲氧基二苯乙烯
  参考文献：
  名称：

  合成甲氧基化白藜芦醇类似物的 CYP1 活化和抗癌特性

  摘要：

  天然存在的二苯乙烯类化合物，如 （E）-二苯乙烯类白藜芦醇和 （Z）-二苯乙烯类化合物 combretastatin A4，已被认为是开发抗癌药物的有前途的先导化合物。已知二苯乙烯类化合物的抗肿瘤特性受细胞色素 P450 酶 CYP1A1 和 CYP1B1 的调节，这有助于肝外 I 期外源性物质和药物代谢。合成白藜芦醇的 34 种甲基醚类似物，并在一组人乳腺细胞系上使用 MTT 细胞增殖测定评估其抗癌特性。表达 CYP1 的乳腺肿瘤细胞系比不具有 CYP1 活性的细胞系受白藜芦醇类似物的影响明显更强。使用分离的 CYP1 酶的代谢研究提供了进一步的证据，证明 （E）-二苯乙烯类化合物可以成为这些酶的底物。通过与合成标准品和 LC-MS 共洗脱研究进行比较来确认代谢产物的结构。最有前途的二苯乙烯类化合物是 （E）-4,3′，4′，5′-四甲氧基二苯乙烯 （DMU212）。该化合物本身显示出低至中度的细胞毒性，但在

  DOI：

  10.3390/molecules29020423
• 作为产物：
  描述：

  4-[[(1,1-二甲基乙基)二甲基甲硅烷基]氧基]-苯甲醇 在 sodium hexamethyldisilazane 、 lithium bromide 作用下， 以 四氢呋喃 为溶剂， 反应 46.5h， 生成 (E)-1-<4-<(tert-butyldimethylsilyl)oxy>phenyl>-2-(3,4,5-trimethoxyphenyl)ethene
  参考文献：
  名称：

  Potential Photoaffinity Labels for Tubulin. Synthesis and Evaluation of Diazocyclohexadienone and Azide Analogs of Colchicine, Combretastatin, and 3,4,5-Trimethoxybiphenyl

  摘要：

  Analogs of tubulin assembly inhibitors such as colchicine, combretastatin, and 3,4,5-trimethoxybiphenyl which incorporate a 6-diazo-2,4-cyclohexadienone (o-quinone diazide) ring have been synthesized and characterized. The compounds synthesized include 6-diazo-4-(2',3',4'-trimethoxyphenyl)cyclohexa-2,4-dien-1-one and its 3-methyl and 3-ethyl analogs (1a-c), 6-diazo-3-(2,3,4-trimethoxyphenyl)-2,4-cyclohexadien-1-one and its 4-methyl and 4-ethyl derivatives (2a-c), 4-[Z-2-(3',4',5'-trimethoxyphenyl)ethenyl]-6-diazocyclohexa-2,4-dienone (3), 3-[Z-2-(3',4',5'-trimethoxyphenyl)ethenyl]-6-diazocyclohexa-2,4-dien-1-one (4), the corresponding dihydro derivatives (5, 6) and two isomeric diazocyclohexadienones derived from N-acetylcolchinol (7, 8). Compounds in which the cyclohexadienone oxygen is approximately isostructural with carbonyl or hydroxy functions of the parent compounds exhibit good activity in the tubulin assembly inhibition assay. 2'-Alkyl-4'azido-3,4,5-trimethoxy-1,1'-biphenyls also show good activity as tubulin assembly inhibitors.

  DOI：

  10.1021/jo00094a048

文献信息

• Synthesis and evaluation of stilbene and dihydrostilbene derivatives as potential anticancer agents that inhibit tubulin polymerization
  作者：Mark Cushman、Dhanapalan Nagarathnam、D. Gopal、Asit K. Chakraborti、Chii M. Lin、Ernest Hamel

  DOI：10.1021/jm00112a036

  日期：1991.8

  An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, and MLM melanoma. Several cis-stilbenes, structurally similar to combretastatins, were highly cytotoxic in all five cell lines and these were also found to be active as inhibitors of tubulin polymerization. The most active compounds also inhibited the binding of colchicine to tubulin. The most potent of the new compounds, both as a tubulin polymerization inhibitor and as a cytotoxic agent, was (Z)-1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene (5a). This substance was almost as potent as combretastatin A-4 (1a), the most active of the combretastatins, as a tubulin polymerization inhibitor. Compound 5a was found to be approximately 140 times more cytotoxic against HT-29 colon adenocarcinoma cells and about 10 times more cytotoxic against MCF-7 breast carcinoma cells than combretastatin A-4. However, 5a was found to be about 20 times less cytotoxic against A-549 lung carcinoma cells, 30 times less cytotoxic against SKMEL-5 melanoma cells, and 7 times less cytotoxic against MLM melanoma cells than combretastatin A-4. The relative potencies 5a > 8a > 6a for the cis, dihydro, and trans compounds, respectively, as inhibitors of tubulin polymerization are in agreement with the relative potencies previously observed for combretastatin A-4 (1a), dihydrocombretastatin A-4 (1c), and trans-combretastatin A-4 (1b). The relative potencies 5a > 8a > 6a were also reflected in the results of the cytotoxicity assays. Structure-activity relationships of this group of compounds are also discussed.
• Anticancer effects of the metabolic products of the resveratrol analogue, DMU-212: Structural requirements for potency
  作者：Vasilis P. Androutsopoulos、Ketan C. Ruparelia、Athanasios Papakyriakou、Harilaos Filippakis、Aristeidis M. Tsatsakis、Demetrios A. Spandidos

  DOI：10.1016/j.ejmech.2011.03.049

  日期：2011.6

  The methoxylated trans-stilbene resveratrol analogue, (E)-3,4,5,4'-tetramethoxystilbene (1), has shown promising antiproliferative activity in in vitro cell line and in vivo models. In vivo I gives rise to several metabolic products through demethylation or hydroxylation reactions at the stilbene moiety. In the present study we examined the anticancer activity of 1 and the metabolites (E)-3'-hydroxy-3,4,5,4'-tetramethoxystilbene (2), (E)-4'-hydroxy-3,4,5-trimethoxystilbene (3), (E)-4-hydroxy-3,5,4'-trimethoxystilbene (4) and (E)-3-hydroxy-4,5,4'-trimethoxystilbene (5) by means of cell viability testing, cell cycle analysis, immunostaining and Western blotting. Compounds 1 and 2 exhibited submicromolar toxicity in MCF-7 breast adenocarcinoma and HepG2 hepatoma cells, whereas 3, 4 and 5 were inactive in terms of inhibition of cellular proliferation. Incubation with 1 or 2 at 10 mu M for 24 h induced apoptosis and G2/M cell cycle arrest in MCF-7 and HepG2 cells. Immunostaining of MCF-7 cells for beta-tubulin in the presence of either 1 or 2 revealed shorter localization of the protein around the nucleus, as compared to control cells. Western blot analyses further demonstrated that treatment with either 1 or 2 at concentrations between 30 and 50 mu M for 24 h caused a downregulation in the levels of beta-tubulin and cyclin D1 expression and an upregulation in the levels of p53 expression in MCF-7 and HepG2 cells. 2 further increased the ratio of mRNA levels of the apoptosis-related genes Bax/Bcl-xL in both MCF-7 and HepG2 cells in a dose-dependent manner. We conclude that 2 inhibits HepG2 and MCF-7 cellular proliferation by inducing apoptosis and G2/M arrest through p53 and Bax/Bcl-xL upregulation. Our findings further demonstrate that trimethoxy substitutions along with the presence of a methoxy group at position 4' are necessary for retaining the activity of 1. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Potential Photoaffinity Labels for Tubulin. Synthesis and Evaluation of Diazocyclohexadienone and Azide Analogs of Colchicine, Combretastatin, and 3,4,5-Trimethoxybiphenyl
  作者：John D. Olszewski、Mary Marshalla、Michal Sabat、Richard J. Sundberg

  DOI：10.1021/jo00094a048

  日期：1994.7

  Analogs of tubulin assembly inhibitors such as colchicine, combretastatin, and 3,4,5-trimethoxybiphenyl which incorporate a 6-diazo-2,4-cyclohexadienone (o-quinone diazide) ring have been synthesized and characterized. The compounds synthesized include 6-diazo-4-(2',3',4'-trimethoxyphenyl)cyclohexa-2,4-dien-1-one and its 3-methyl and 3-ethyl analogs (1a-c), 6-diazo-3-(2,3,4-trimethoxyphenyl)-2,4-cyclohexadien-1-one and its 4-methyl and 4-ethyl derivatives (2a-c), 4-[Z-2-(3',4',5'-trimethoxyphenyl)ethenyl]-6-diazocyclohexa-2,4-dienone (3), 3-[Z-2-(3',4',5'-trimethoxyphenyl)ethenyl]-6-diazocyclohexa-2,4-dien-1-one (4), the corresponding dihydro derivatives (5, 6) and two isomeric diazocyclohexadienones derived from N-acetylcolchinol (7, 8). Compounds in which the cyclohexadienone oxygen is approximately isostructural with carbonyl or hydroxy functions of the parent compounds exhibit good activity in the tubulin assembly inhibition assay. 2'-Alkyl-4'azido-3,4,5-trimethoxy-1,1'-biphenyls also show good activity as tubulin assembly inhibitors.
• CYP1-Activation and Anticancer Properties of Synthetic Methoxylated Resveratrol Analogues
  作者：Ketan C. Ruparelia、Keti Zeka、Kenneth J. M. Beresford、Nicola E. Wilsher、Gerry A. Potter、Vasilis P. Androutsopoulos、Federico Brucoli、Randolph R. J. Arroo

  DOI：10.3390/molecules29020423

  日期：——

  (Z)-stilbenoid combretastatin A4, have been considered as promising lead compounds for the development of anticancer drugs. The antitumour properties of stilbenoids are known to be modulated by cytochrome P450 enzymes CYP1A1 and CYP1B1, which contribute to extrahepatic phase I xenobiotic and drug metabolism. Thirty-four methyl ether analogues of resveratrol were synthesised, and their anticancer properties were

  天然存在的二苯乙烯类化合物，如 （E）-二苯乙烯类白藜芦醇和 （Z）-二苯乙烯类化合物 combretastatin A4，已被认为是开发抗癌药物的有前途的先导化合物。已知二苯乙烯类化合物的抗肿瘤特性受细胞色素 P450 酶 CYP1A1 和 CYP1B1 的调节，这有助于肝外 I 期外源性物质和药物代谢。合成白藜芦醇的 34 种甲基醚类似物，并在一组人乳腺细胞系上使用 MTT 细胞增殖测定评估其抗癌特性。表达 CYP1 的乳腺肿瘤细胞系比不具有 CYP1 活性的细胞系受白藜芦醇类似物的影响明显更强。使用分离的 CYP1 酶的代谢研究提供了进一步的证据，证明 （E）-二苯乙烯类化合物可以成为这些酶的底物。通过与合成标准品和 LC-MS 共洗脱研究进行比较来确认代谢产物的结构。最有前途的二苯乙烯类化合物是 （E）-4,3′，4′，5′-四甲氧基二苯乙烯 （DMU212）。该化合物本身显示出低至中度的细胞毒性，但在