二-(叔-丁基-二甲基硅烷基)姜黄素 | 1134639-23-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 中文名称: 二-(叔-丁基-二甲基硅烷基)姜黄素
• 英文名称: (1E,4Z,6E)-1,7-bis(4-((tert-butyldimethylsilyl)oxy)-3-methoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one
• 英文别名: Di-(tert-Butyl-dimethylsilyl) Curcumin；(1E,4Z,6E)-1,7-bis[4-[tert-butyl(dimethyl)silyl]oxy-3-methoxyphenyl]-5-hydroxyhepta-1,4,6-trien-3-one
• CAS: 1134639-23-8
• 化学式: C₃₃H₄₈O₆Si₂
• 分子量: 596.912
• InChiKey: YTANFSVGWHEWKY-MVRVVBEHSA-N

物化性质

• 熔点：
  138-140oC
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  9.21
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

制备方法与用途

Di-(tert-Butyl-diMethylsilyl) Curcumin 是一种天然酚类化合物，具有抗炎和抗氧化特性。它能诱导癌细胞凋亡，并抑制佛波酯诱导的蛋白激酶 C (PKC) 活性。研究表明，它还能抑制外周血单核细胞和肺泡巨噬细胞产生炎性细胞因子。

反应信息

• 作为反应物：
  描述：

  1-(ferrocene)prop-2-yn-1-one 、 二-(叔-丁基-二甲基硅烷基)姜黄素 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以26%的产率得到(1E,4Z,6E)-1,7-bis(3-methoxy-4-((tert-butyldimethylsilyl)oxy)phenyl)-4[(E)-1-ferrocenylprop-2-en-1-one]-3-hydroxyhepta-1,4,6-trien-5-one
  参考文献：
  名称：

  Synthesis of the First Ferrocenyl Derivatives of Curcuminoids

  摘要：

  The synthesis of curcuminoids covalently bound to a ferrocenyl moiety was investigated using two strategies: a ferrocenyl unit was incorporated during the synthesis of 3,4-dimethylcurcumin using a Knoevenagel condensation, and the enolates of 3,5-dimethylcurcumin and curcumin, previously protected, underwent a 1,4-addition on ferrocenyl propynone.

  DOI：

  10.1021/om900003g
• 作为产物：
  描述：

  3-叔-丁基二甲基硅氧基-4-甲氧基苯甲醛 、 乙酰丙酮 在 硼酸三丁酯 、 氧化硼 、 正丁胺 作用下， 以 乙酸乙酯 为溶剂， 反应 6.5h， 生成 二-(叔-丁基-二甲基硅烷基)姜黄素
  参考文献：
  名称：

  Design, synthesis, and evaluation of curcumin derivatives as Nrf2 activators and cytoprotectors against oxidative death

  摘要：

  Activation of nuclear factor erythroid-2-related factor 2 (Nrf2) has been proven to be an effective means to prevent the development of cancer, and natural curcumin stands out as a potent Nrf2 activator and cancer chemopreventive agent. In this study, we synthesized a series of curcumin analogs by introducing the geminal dimethyl substituents on the active methylene group to find more potent Nrf2 activators and cytoprotectors against oxidative death. The geminally dimethylated and catechol-type curcumin analog (compound 3) was identified as a promising lead molecule in terms of its increased stability and cytoprotective activity against the tert-butyl hydroperoxide (t-BHP)-induced death of HepG2 cells. Mechanism studies indicate that its cytoprotective effects are mediated by activating the Nrf2 signaling pathway in the Michael acceptor- and catechol-dependent manners. Additionally, we verified by using copper and iron ion chelators that the two metal ion-mediated oxidations of compound 3 to its corresponding electrophilic sigma-quinone, contribute significantly to its Nrf2-dependent cytoprotection. This work provides an example of successfully designing natural curcumin-directed Nrf2 activators by a stability-increasing and proelectrophilic strategy. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.04.008

文献信息

• Influence of side-chain changes on histone deacetylase inhibitory and cytotoxicity activities of curcuminoid derivatives
  作者：La-or Somsakeesit、Thanaset Senawong、Pakit Kumboonma、Somprasong Saenglee、Arunta Samankul、Gulsiri Senawong、Chavi Yenjai、Chanokbhorn Phaosiri

  DOI：10.1016/j.bmcl.2020.127171

  日期：2020.6

  Using curcuminoids as lead compounds, fifty-nine curcuminoid derivatives with different side chains at the phenolic moiety were synthesized. All compounds were investigated for their histone deacetylase (HDAC) inhibitory activities. The potent pan-HDAC inhibitors were further tested against three human cancer cell lines including Hela, HCT116 and MCF-7 with MTT-based assay. The bisethylamide 4z and the mono-sec-butyl derivative 5j manifested good antiproliferative activities against HCT116 cancer cells with the IC50 values as 14.60 +/- 1.19 mu g/mL and 7.33 +/- 0.98 mu g/mL, respectively. Molecular docking study of both compounds with Class I HDACs revealed that the compounds might bind tightly to the binding pocket of HDAC2. These findings suggested that these compounds can be putative candidates for the development of anticancer drugs via inhibiting HDACs.
• Design, synthesis, and evaluation of curcumin derivatives as Nrf2 activators and cytoprotectors against oxidative death
  作者：Zhi-Shan Tu、Qi Wang、Dan-Dan Sun、Fang Dai、Bo Zhou

  DOI：10.1016/j.ejmech.2017.04.008

  日期：2017.7

  Activation of nuclear factor erythroid-2-related factor 2 (Nrf2) has been proven to be an effective means to prevent the development of cancer, and natural curcumin stands out as a potent Nrf2 activator and cancer chemopreventive agent. In this study, we synthesized a series of curcumin analogs by introducing the geminal dimethyl substituents on the active methylene group to find more potent Nrf2 activators and cytoprotectors against oxidative death. The geminally dimethylated and catechol-type curcumin analog (compound 3) was identified as a promising lead molecule in terms of its increased stability and cytoprotective activity against the tert-butyl hydroperoxide (t-BHP)-induced death of HepG2 cells. Mechanism studies indicate that its cytoprotective effects are mediated by activating the Nrf2 signaling pathway in the Michael acceptor- and catechol-dependent manners. Additionally, we verified by using copper and iron ion chelators that the two metal ion-mediated oxidations of compound 3 to its corresponding electrophilic sigma-quinone, contribute significantly to its Nrf2-dependent cytoprotection. This work provides an example of successfully designing natural curcumin-directed Nrf2 activators by a stability-increasing and proelectrophilic strategy. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Synthesis of the First Ferrocenyl Derivatives of Curcuminoids
  作者：Anusch Arezki、Emilie Brulé、Gérard Jaouen

  DOI：10.1021/om900003g

  日期：2009.3.23

  The synthesis of curcuminoids covalently bound to a ferrocenyl moiety was investigated using two strategies: a ferrocenyl unit was incorporated during the synthesis of 3,4-dimethylcurcumin using a Knoevenagel condensation, and the enolates of 3,5-dimethylcurcumin and curcumin, previously protected, underwent a 1,4-addition on ferrocenyl propynone.