2-methoxy-1-methyl-4-((trimethylsilyl)oxy)cyclohex-3-enecarbonitrile | 134837-19-7

• 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-methyl-4-((trimethylsilyl)oxy)cyclohex-3-enecarbonitrile
• 英文别名: 2-Methoxy-1-methyl-4-trimethylsilyloxycyclohex-3-ene-1-carbonitrile
• CAS: 134837-19-7
• 化学式: C₁₂H₂₁NO₂Si
• 分子量: 239.39
• InChiKey: BJQRJHOCZQJWFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.06
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methoxy-1-methyl-4-((trimethylsilyl)oxy)cyclohex-3-enecarbonitrile 在 D(+)-10-樟脑磺酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醚 、 正庚烷 、 乙基苯 为溶剂， 反应 61.33h， 生成 3-methyl-6-oxocyclohex-4-ene-1,3-dicarbonitrile
  参考文献：
  名称：

  Synthesis, Chemical Reactivity as Michael Acceptors, and Biological Potency of Monocyclic Cyanoenones, Novel and Highly Potent Anti-inflammatory and Cytoprotective Agents

  摘要：

  Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-alpha and IL-1 beta with potencies that are higher than those of bardoxolone methyl and TBE-31.

  DOI：

  10.1021/jm3003922
• 作为产物：
  描述：

  反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯 、 甲基丙烯腈 以 甲苯 为溶剂， 反应 46.0h， 生成 2-methoxy-1-methyl-4-((trimethylsilyl)oxy)cyclohex-3-enecarbonitrile
  参考文献：
  名称：

  Synthesis, Chemical Reactivity as Michael Acceptors, and Biological Potency of Monocyclic Cyanoenones, Novel and Highly Potent Anti-inflammatory and Cytoprotective Agents

  摘要：

  Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-alpha and IL-1 beta with potencies that are higher than those of bardoxolone methyl and TBE-31.

  DOI：

  10.1021/jm3003922

文献信息

• Acid catalyzed rearrangements of 4-methyl-4-cyanocyclohexadienone
  作者：John N. Marx、Joe Zuerker、Young-sook Paik Hahn

  DOI：10.1016/0040-4039(91)85002-m

  日期：1991.4

  Acid-catalyzed dienone-phenol rearrangement reactions of 4-methyl-4-cyanocyclohexadienone occur very slowly and give either fragmentation or methyl group migration, not cyano group migration, under non-nucleophilic strongly acidic conditions.
• Inokuchi; Okano; Miyamoto, Synlett, 2000, # 11, p. 1549 - 1552
  作者：Inokuchi、Okano、Miyamoto、Bte Madon、Takagi

  DOI：——

  日期：——
• Synthesis, Chemical Reactivity as Michael Acceptors, and Biological Potency of Monocyclic Cyanoenones, Novel and Highly Potent Anti-inflammatory and Cytoprotective Agents
  作者：Suqing Zheng、Y. R. Santosh Laxmi、Emilie David、Albena T. Dinkova-Kostova、Katherine H. Shiavoni、Yanqing Ren、Ying Zheng、Isaac Trevino、Ronald Bumeister、Iwao Ojima、W. Christian Wigley、James B. Bliska、Dale F. Mierke、Tadashi Honda

  DOI：10.1021/jm3003922

  日期：2012.5.24

  Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-alpha and IL-1 beta with potencies that are higher than those of bardoxolone methyl and TBE-31.