(1aS,2aS,8aR)-5-氨基-2a-甲氧基-1,6-二甲基-3-甲亚基-1,1a,2,2a,3,8a-六氢吖丙烯并[2',3':4,5]吡咯并[1,2-a]吲哚-4,7-二酮 | 73843-26-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (1aS,2aS,8aR)-5-氨基-2a-甲氧基-1,6-二甲基-3-甲亚基-1,1a,2,2a,3,8a-六氢吖丙烯并[2',3':4,5]吡咯并[1,2-a]吲哚-4,7-二酮
• 英文名称: 8-ethynyl-8-methyl-1,4-dioxaspiro[4.5]dec-6-ene
• CAS: 73843-26-2
• 化学式: C₁₁H₁₄O₂
• 分子量: 178.231
• InChiKey: DMQIRQOKOMWGRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1aS,2aS,8aR)-5-氨基-2a-甲氧基-1,6-二甲基-3-甲亚基-1,1a,2,2a,3,8a-六氢吖丙烯并[2',3':4,5]吡咯并[1,2-a]吲哚-4,7-二酮 在 盐酸 作用下， 以 水 、 丙酮 为溶剂， 反应 2.0h， 以90%的产率得到4-乙炔基-4-甲基环己-2-烯酮
  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：

  3-乙氧基-6-甲基-2-环己烯-1-酮 在 正丁基锂 、 二异丁基氢化铝 、 对甲苯磺酸 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 、 苯 为溶剂， 反应 39.5h， 生成 (1aS,2aS,8aR)-5-氨基-2a-甲氧基-1,6-二甲基-3-甲亚基-1,1a,2,2a,3,8a-六氢吖丙烯并[2',3':4,5]吡咯并[1,2-a]吲哚-4,7-二酮
  参考文献：
  名称：

  DICHLOROVINYLATION OF AN ENOLATE: 8-ETHYNYL-8-METHYL-1,4-DIOXASPIRO[4.5]DEC-6-ENE

  摘要：

  DOI：

  10.15227/orgsyn.064.0073

文献信息

• KENDE, A. S.;FLUDZINSKI, P., ORG. SYNTH. VOL. 64, NEW YORK E. A.,(1986) 73-79
  作者：KENDE, A. S.、FLUDZINSKI, P.

  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.
• DICHLOROVINYLATION OF AN ENOLATE: 8-ETHYNYL-8-METHYL-1,4-DIOXASPIRO[4.5]DEC-6-ENE
  作者：Kende, Andrew S.、Fludzinski, Pawel

  DOI：10.15227/orgsyn.064.0073

  日期：——