(E)-1-(3-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxyphenyl)-2-(4-hydroxyphenyl)ethene

• 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-(3-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxyphenyl)-2-(4-hydroxyphenyl)ethene
• 英文别名: 3-O-tert-butyldimethylsilyl resveratrol；3-[tert-butyl(dimethyl)silyl]oxy-5-[(E)-2-(4-hydroxyphenyl)ethenyl]phenol
• 化学式: C₂₀H₂₆O₃Si
• 分子量: 342.51
• InChiKey: QZSCKTHKURECDO-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.65
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-1-(3-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxyphenyl)-2-(4-hydroxyphenyl)ethene 在 三甲基铵三氧化硫共聚物 、 三乙胺 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Selective Synthesis and Biological Evaluation of Sulfate-Conjugated Resveratrol Metabolites

  摘要：

  Five resveratrol sulfate metabolites were synthesized and assessed for activities known to be mediated by resveratrol: inhibition of tumor necrosis factor (TNF)alpha induced NF kappa B activity, cylcooxygenases (COX-1 and COX-2), aromatase, nitric oxide production in endotoxin-stimulated macrophages, proliferation of KB or MCF7 cells, induction of quinone reductase I (QRI), accumulation in the sub-G, phase of the cell cycle, and quenching of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. Two metabolites showed activity in these assays; the 3-sulfate exhibited QRI induction, DPPH free radical scavenging, and COX-1 and COX-2 inhibitory activities and the 4'-sulfate inhibited NF kappa B induction, as well as COX-1 and COX-2 activities. Resveratrol and its 3'-sulfate and 4-sulfate inhibit NO production by NO scavenging and down-regulation of iNOS expression in RAW 264.7 cells. Resveratrol sulfates displayed low antiproliferative activity and negligible uptake in MCF7 cells.

  DOI：

  10.1021/jm100274c
• 作为产物：
  描述：

  白藜芦醇 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 以23%的产率得到(E)-1-(3-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxyphenyl)-2-(4-hydroxyphenyl)ethene
  参考文献：
  名称：

  甲硅烷基白藜芦醇衍生物作为神经退行性疾病和神经系统疾病的潜在治疗剂

  摘要：

  在食物中发现的天然酚类化合物已证明对多种病理具有有趣的预防和治疗作用。事实上，其中一些，例如白藜芦醇 (RES)，已经在临床试验中进行了检查。然而，它们的成功很少，主要是因为它们的生物利用度低。在这项研究中，我们意外地发现O-甲硅烷基 RES 衍生物比白藜芦醇本身具有更好的神经保护活性，并决定探索它们作为治疗神经退行性疾病和神经系统疾病的潜在药物。我们还设计并制备了一系列O-甲硅烷基RES前药以提高其生物利用度。我们发现二三乙基甲硅烷基和二三异丙基甲硅烷基 RES 衍生物在体外效果更好神经保护剂和抗炎剂比 RES。在这些衍生物及其相应的酰基-、糖基-和氨基甲酰基-前药中，3,5-三乙基甲硅烷基-4'-（6″-辛酰基吡喃葡萄糖基）白藜芦醇26在斑马鱼胚胎中表现出最佳的毒性和神经保护活性。化合物26还能够以与 RES 类似的方式减少亨廷顿病 3-硝基丙酸小鼠模型中运动协调性的丧失。然而，与 RES

  DOI：

  10.1016/j.ejmech.2021.113655

文献信息

• Synthesis of Mono- and Di-<i>O</i>-β-<scp>d</scp>-glucopyranoside Conjugates of (<i>E</i>)-Resveratrol
  作者：Zhaojun Zhang、Biao Yu、Richard Schmidt

  DOI：10.1055/s-2006-926394

  日期：2006.4

  Starting from the commercially available natural product (E)-resveratrol (1), the four selectively tert-butyldimethylsilyl (TBS) protected (E)-resveratrols 6-9 were prepared by one reaction. Using 6-9 as glucosyl acceptors and trifluoroacetimidate 11 as glucosyl donor, three bioactive natural glucopyranoside conjugates of (E)-resveratrol 2-4 and one novel compound (5) were efficiently prepared in two steps.

  从市售天然产物（E）-白藜芦醇（1）出发，通过一步反应制备了四种选择性叔丁基二甲基硅基（TBS）保护的（E）-白藜芦醇衍生物 6-9。以 6-9 作为糖基受体，三氟乙酰亚胺 11 作为糖基供体，高效地通过两步反应合成了三种具有生物活性的天然葡萄糖苷（E）-白藜芦醇偶联物 2-4 和一个新化合物（5）。
• Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites
  作者：Eva Falomir、Ricardo Lucas、Pablo Peñalver、Rosa Martí-Centelles、Alexia Dupont、Alberto Zafra-Gómez、Miguel Carda、Juan C. Morales

  DOI：10.1002/cbic.201600084

  日期：2016.7.15

  Improved resveratrol activity: Glucosylated resveratrol prodrugs and resveratrol sulfate metabolites show improved anti‐proliferative and anti‐angiogenic activity in comparison to resveratrol itself. These results suggest resveratrol derivatives as potential drugs and confirm that resveratrol sulfate metabolites contribute to the in vivo biological activity observed for the parent compound.

  改善白藜芦醇活性：与白藜芦醇本身相比，糖基化白藜芦醇前药和硫酸白藜芦醇代谢物显示出改善的抗增殖和抗血管生成活性。这些结果表明白藜芦醇衍生物是潜在的药物，并证实硫酸白藜芦醇代谢物有助于母体化合物观察到的体内生物活性。
• Preventive Oral Treatment with Resveratrol Pro-prodrugs Drastically Reduce Colon Inflammation in Rodents
  作者：Mar Larrosa、Joao Tomé-Carneiro、María J. Yáñez-Gascón、David Alcántara、María V. Selma、David Beltrán、María T. García-Conesa、Cristina Urbán、Ricardo Lucas、Francisco Tomás-Barberán、Juan C. Morales、Juan Carlos Espín

  DOI：10.1021/jm1007006

  日期：2010.10.28

  There is no pharmaceutical or definitive surgical cure for inflammatory bowel diseases (IBDs). The naturally occurring polyphenol resveratrol exerts anti-inflammatory properties. However, its rapid metabolism diminishes its effectiveness in the colon. The design of prodrugs to targeting active molecules to the colon provides an opportunity for therapy of IBDs. Herein we explore the efficacy of different resveratrol prodrugs and pro-prodrugs to ameliorate colon inflammation in the murine dextran sulfate sodium (DSS) model. Mice fed with a very low dose (equivalent to 10 mg for a 70 kg-person) of either resveratrol-3-O-(6'-O-butanoyl)-beta-D-glucopyranoside (6) or resveratrol-3-O-(6'-O-octanoyl)-beta-D-glucopyranoside (7) did not develop colitis symptoms and improved 6-fold the disease activity index (DAI) compared to resveratrol. Our results indicate that these pro-prodrugs exerted a dual effect: (1) they prevented the rapid metabolism of resveratrol and delivered higher quantities of resveratrol to the colon and (2) they reduced mucosal barrier imbalance and prevented diarrhea, which consequently facilitated the action of the delivered resveratrol in the colon mucosa.
• Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases
  作者：Efres Belmonte-Reche、Pablo Peñalver、Marta Caro-Moreno、María Luisa Mateos-Martín、Norma Adán、Mario Delgado、Elena González-Rey、Juan Carlos Morales

  DOI：10.1016/j.ejmech.2021.113655

  日期：2021.11

  resveratrol itself and decided to explore them as potential drugs for neurodegenerative and neurological diseases. We have also designed and prepared a series of O-silyl RES prodrugs to improve their bioavailability. We found that di-triethylsilyl and di-triisopropylsilyl RES derivatives were better in vitro neuroprotective and anti-inflammatory agents than RES. Among these derivatives and their corresponding

  在食物中发现的天然酚类化合物已证明对多种病理具有有趣的预防和治疗作用。事实上，其中一些，例如白藜芦醇 (RES)，已经在临床试验中进行了检查。然而，它们的成功很少，主要是因为它们的生物利用度低。在这项研究中，我们意外地发现O-甲硅烷基 RES 衍生物比白藜芦醇本身具有更好的神经保护活性，并决定探索它们作为治疗神经退行性疾病和神经系统疾病的潜在药物。我们还设计并制备了一系列O-甲硅烷基RES前药以提高其生物利用度。我们发现二三乙基甲硅烷基和二三异丙基甲硅烷基 RES 衍生物在体外效果更好神经保护剂和抗炎剂比 RES。在这些衍生物及其相应的酰基-、糖基-和氨基甲酰基-前药中，3,5-三乙基甲硅烷基-4'-（6″-辛酰基吡喃葡萄糖基）白藜芦醇26在斑马鱼胚胎中表现出最佳的毒性和神经保护活性。化合物26还能够以与 RES 类似的方式减少亨廷顿病 3-硝基丙酸小鼠模型中运动协调性的丧失。然而，与 RES
• Selective Synthesis and Biological Evaluation of Sulfate-Conjugated Resveratrol Metabolites
  作者：Juma Hoshino、Eun-Jung Park、Tamara P. Kondratyuk、Laura Marler、John M. Pezzuto、Richard B. van Breemen、Shunyan Mo、Yongchao Li、Mark Cushman

  DOI：10.1021/jm100274c

  日期：2010.7.8

  Five resveratrol sulfate metabolites were synthesized and assessed for activities known to be mediated by resveratrol: inhibition of tumor necrosis factor (TNF)alpha induced NF kappa B activity, cylcooxygenases (COX-1 and COX-2), aromatase, nitric oxide production in endotoxin-stimulated macrophages, proliferation of KB or MCF7 cells, induction of quinone reductase I (QRI), accumulation in the sub-G, phase of the cell cycle, and quenching of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. Two metabolites showed activity in these assays; the 3-sulfate exhibited QRI induction, DPPH free radical scavenging, and COX-1 and COX-2 inhibitory activities and the 4'-sulfate inhibited NF kappa B induction, as well as COX-1 and COX-2 activities. Resveratrol and its 3'-sulfate and 4-sulfate inhibit NO production by NO scavenging and down-regulation of iNOS expression in RAW 264.7 cells. Resveratrol sulfates displayed low antiproliferative activity and negligible uptake in MCF7 cells.