2-methoxy-1-triisopropylsilylethynyl-4-trimethylsilyloxy-3-cyclohexene-1-carboxaldehyde

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 2-methoxy-1-triisopropylsilylethynyl-4-trimethylsilyloxy-3-cyclohexene-1-carboxaldehyde
• 英文别名: 2-methoxy-1-((triisopropylsilyl)ethynyl)-4-((trimethylsilyl)oxy)cyclohex-3-enecarbaldehyde；2-Methoxy-4-trimethylsilyloxy-1-[2-tri(propan-2-yl)silylethynyl]cyclohex-3-ene-1-carbaldehyde
• 化学式: C₂₂H₄₀O₃Si₂
• 分子量: 408.729
• InChiKey: DTQNKINANDSLSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.94
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methoxy-1-triisopropylsilylethynyl-4-trimethylsilyloxy-3-cyclohexene-1-carboxaldehyde 在 正丁基锂 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 正庚烷 、 乙基苯 、 1,2-二氯乙烷 为溶剂， 反应 12.83h， 生成 2-oxo-5-((triisopropylsilyl)ethynyl)-5-((trimethylsilyl)ethynyl)cyclohex-3-enecarbonitrile
  参考文献：
  名称：

  New Monocyclic, Bicyclic, and Tricyclic Ethynylcyanodienones as Activators of the Keap1/Nrf2/ARE Pathway and Inhibitors of Inducible Nitric Oxide Synthase

  摘要：

  A monocyclic compound 3 (3-ethynyl-3-methyl-6-oxocyclohexa-1,4-dienecarbonitrile) is a highly reactive Michael acceptor leading to reversible adducts with nucleophiles, which displays equal or greater potency than the pentacyclic triterpenoid CDDO in inflammation and carcinogenesis related assays. Recently, reversible covalent drugs, which bind with protein targets but not permanently, have been gaining attention because of their unique features. To explore such reversible covalent drugs, we have synthesized monocyclic, bicyclic, and tricyclic compounds containing 3 as an electrophilic fragment and evaluated them as activators of the Keap1/Nrf2/ARE pathway and inhibitors of iNOS. Notably, these compounds maintain the unique features of the chemical reactivity and biological potency of 3. Among them, a monocyclic compound 5 is the most potent in these assays while a tricyclic compound 14 displays a more robust and specific activation profile compared to 5. In conclusion, we demonstrate that 3 is a useful electrophilic fragment for exploring reversible covalent drugs.

  DOI：

  10.1021/acs.jmedchem.5b00393
• 作为产物：
  描述：

  反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯 、 2,2-dimethyl-5-(triisopropylsilylethynyl)-4H-1,3-dioxin 在 对苯二酚 作用下， 以 甲苯 为溶剂， 反应 5.0h， 以100%的产率得到2-methoxy-1-triisopropylsilylethynyl-4-trimethylsilyloxy-3-cyclohexene-1-carboxaldehyde
  参考文献：
  名称：

  由5-（三氟甲磺酰氧基）-4 H -1,3-二恶英制备2-烷基-和2-酰基丙烯醛：一种多功能的丙烯醛α-阳离子合成物

  摘要：

  5-（三氟甲磺酰氧基）-4 H -1,3-二恶英（3）参与各种与铜酸盐试剂的亲核取代反应，或参与钯催化的交叉偶联反应以提供5-取代的4 H -1,3-二恶英5。在热解后，这些化合物进行容易的逆转录加成反应以生成相应的2-取代的丙烯醛，如果需要的话，可以将其与二烯或异二烯体原位捕获。特别地，可以使用该方法产生迄今未知的2-酰基丙烯醛，并用烯醇醚捕集以提供5-酰基-3,4-二氢-2 H-吡喃（6g，h），这是许多天然产物共有的亚结构单元。

  DOI：

  10.1016/s0040-4020(00)00872-3

文献信息

• Preparation of 2-Alkyl- and 2-Acylpropenals from 5-(Trifluoromethanesulfonyloxy)-4H-1,3-dioxin: A Versatile Acrolein α-Cation Synthon
  作者：Stephen P. Fearnley、Raymond L. Funk、Robert J. Gregg

  DOI：10.1016/s0040-4020(00)00872-3

  日期：2000.12

  catalyzed cross-coupling reactions to provide 5-substituted-4H-1,3-dioxins 5. Upon thermolysis, these compounds undergo facile retrocycloaddition reactions to generate the corresponding 2-substituted acroleins which, if necessary, can be trapped in situ with dienes or heterodienophiles. In particular, the heretofore unknown 2-acylacroleins can be generated using this methodology and trapped with enol ethers

  5-（三氟甲磺酰氧基）-4 H -1,3-二恶英（3）参与各种与铜酸盐试剂的亲核取代反应，或参与钯催化的交叉偶联反应以提供5-取代的4 H -1,3-二恶英5。在热解后，这些化合物进行容易的逆转录加成反应以生成相应的2-取代的丙烯醛，如果需要的话，可以将其与二烯或异二烯体原位捕获。特别地，可以使用该方法产生迄今未知的2-酰基丙烯醛，并用烯醇醚捕集以提供5-酰基-3,4-二氢-2 H-吡喃（6g，h），这是许多天然产物共有的亚结构单元。
• New Monocyclic, Bicyclic, and Tricyclic Ethynylcyanodienones as Activators of the Keap1/Nrf2/ARE Pathway and Inhibitors of Inducible Nitric Oxide Synthase
  作者：Wei Li、Suqing Zheng、Maureen Higgins、Rocco P. Morra、Anne T. Mendis、Chih-Wei Chien、Iwao Ojima、Dale F. Mierke、Albena T. Dinkova-Kostova、Tadashi Honda

  DOI：10.1021/acs.jmedchem.5b00393

  日期：2015.6.11

  A monocyclic compound 3 (3-ethynyl-3-methyl-6-oxocyclohexa-1,4-dienecarbonitrile) is a highly reactive Michael acceptor leading to reversible adducts with nucleophiles, which displays equal or greater potency than the pentacyclic triterpenoid CDDO in inflammation and carcinogenesis related assays. Recently, reversible covalent drugs, which bind with protein targets but not permanently, have been gaining attention because of their unique features. To explore such reversible covalent drugs, we have synthesized monocyclic, bicyclic, and tricyclic compounds containing 3 as an electrophilic fragment and evaluated them as activators of the Keap1/Nrf2/ARE pathway and inhibitors of iNOS. Notably, these compounds maintain the unique features of the chemical reactivity and biological potency of 3. Among them, a monocyclic compound 5 is the most potent in these assays while a tricyclic compound 14 displays a more robust and specific activation profile compared to 5. In conclusion, we demonstrate that 3 is a useful electrophilic fragment for exploring reversible covalent drugs.