2-(1-hydroxycyclohexylmethyl)-2-cyclopenten-1-one | 872585-01-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(1-hydroxycyclohexylmethyl)-2-cyclopenten-1-one
• 英文别名: 2-Cyclopenten-1-one, 2-(cyclohexylhydroxymethyl)-；2-[cyclohexyl(hydroxy)methyl]cyclopent-2-en-1-one
• CAS: 872585-01-8
• 化学式: C₁₂H₁₈O₂
• 分子量: 194.274
• InChiKey: DSPVFOSPZJSVTN-UHFFFAOYSA-N

物化性质

• 沸点：
  350.9±21.0 °C(Predicted)
• 密度：
  1.128±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(1-hydroxycyclohexylmethyl)-2-cyclopenten-1-one 在 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 丙酸 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 24.17h， 生成 2-hydroxyethyl-2-(2-(cyclohexylmethylene)-3-oxocyclopentyl)acetate
  参考文献：
  名称：

  Anti-inflammatory effects of an optimized PPAR-γ agonist via NF-κB pathway inhibition

  摘要：

  In our previous study, a PPAR-gamma agonist (+)-(R,E)-6a1 was elaborated as an anti-inflammatory lead. However, in silico analysis showed that (+ )-(R,E)-6a1 lacks key hydrogen bonding with Tyr(473) of PPAR-gamma LBD (ligand binding domain). To facilitate additional hydrogen bonding with Tyr(473), a more polar head group was introduced to the structure of (+)-(R,E)-6a1, and we also attempted to synthesize enzymatically stable derivatives. Of the synthetic derivatives, compound (+)-(R,E)-5f showed highest PPAR-gamma transcriptional activity and reasonable metabolic stability. Compound (+)-(R,E)-5f suppressed the expression of pro-inflammatory mediators such as inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and tumor necrosis factor-alpha(TNF-alpha). Reduction of nitric oxide (NO), and ROS was also observed. Compound ( + )-(R,E)-5f was found to suppress the NF-kappa B pathway by inhibiting phosphorylation of IKK (I kappa B kinase), and this may lead to subsequent inhibition of I kappa B alpha (inhibitor of NF-kappa Ba) phosphorylation and inhibition of NF-kappa B activation. These results indicate that (+)-(R,E)-5f exerts anti-inflammatory activity via NF-KB pathway inhibition, and may serve as a potential anti-inflammatory lead.

  DOI：

  10.1016/j.bioorg.2020.103611
• 作为产物：
  描述：

  2-环戊烯酮 、 环己烷基甲醛 在 二甲基苯基磷 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 22.0h， 以70%的产率得到2-(1-hydroxycyclohexylmethyl)-2-cyclopenten-1-one
  参考文献：
  名称：

  A Practical Preparation of 2-Hydroxymethyl-2-cyclopenten-1-one by Morita-Baylis-Hillman Reaction

  摘要：

  三丁基膦或二甲基苯基膦（1-5 mol%）催化2-环戊烯-1-酮（1）与1.2当量福尔马林的Morita-Baylis-Hillman反应顺利进行，得到2-羟甲基-2-环戊烯-1-酮（ 2) 周期短、产量高。反应效率（产率和时间）很大程度上取决于溶剂，在含水 MeOH-CHCl3 溶剂系统的情况下获得最佳结果。

  DOI：

  10.1055/s-2005-916030

文献信息

• A highly α-regioselective In(OTf)3-catalyzed N-nucleophilic substitution of cyclic Baylis–Hillman adducts with aromatic amines
  作者：Yu-Liang Liu、Li Liu、Dong Wang、Yong-Jun Chen

  DOI：10.1016/j.tet.2009.02.048

  日期：2009.4

  The highly α-regioselective N-nucleophilic substitution of B–H adducts bearing five (1a–f) or six-membered ring (5a–e) moieties with aromatic amines (2a–e) was developed under the catalysis of In(OTf)3 (10 mol%). During the reaction the allylic rearrangement from γ-product to α-product occurred, resulting in thermodynamically stable α-product predominately.

  在In（OTf）的催化下，开发了具有芳香族胺（2a - e）的带有五个（1a - f）或六元环（5a - e）部分的B–H加合物的高度α-区域选择性N-亲核取代基。3（10mol％）。在反应过程中，发生了从γ-产物到α-产物的烯丙基重排，主要导致热力学稳定的α-产物。
• Asymmetric Formal [5 + 3] Cycloadditions with Unmodified Morita–Baylis–Hillman Alcohols via Double Activation Catalysis
  作者：Qian-Qian Yang、Xiang Yin、Xiao-Long He、Wei Du、Ying-Chun Chen

  DOI：10.1021/acscatal.8b04942

  日期：2019.2.1

  discovery of a previously unreported activation mode and reaction pathway is important but challenging for the development of asymmetric organocatalysis. Here we disclosed a formal [5 + 3] cycloaddition reaction of unmodified Morita–Baylis–Hillman alcohols from 2-cyclopentenone and aldehydes with cyclic azomethine imines. A double catalytic system, combining chiral primary amine from cinchona alkaloid

  以前未报道的活化方式和反应途径的发现很重要，但对于不对称有机催化的发展却具有挑战性。在这里，我们公开了由2-环戊烯酮和醛与未反应的Morita-Baylis-Hillman醇进行的正式[5 + 3]环加成反应与环甲亚胺亚胺的反应。双催化体系结合了金鸡纳生物碱中的手性伯胺和非手性2-巯基苯甲酸，通过对位阻烯酮底物进行共价双重活化，对化学选择性和对映选择性至关重要。一系列带有大量取代基的三环骨架以中等至高产率产生，并具有良好的立体选择性（高达98％ee，> 19：1 dr）。在实验观察的辅助下，提出了合理的催化机理。
• Acceleration of the Morita−Baylis−Hillman Reaction by a Simple Mixed Catalyst System
  作者：Alejandro Bugarin、Brian T. Connell

  DOI：10.1021/jo900603w

  日期：2009.6.19

  By using a catalytic amount of 4-dimethylaminopyridine (DMAP) as a nucleophile in the presence of an equal amount of tetramethylethylenediamine (TMEDA) and MgI2, Morita-Baylis-Hillman adducts can be obtained in good to excellent yields from various aromatic and aliphatic aldehydes and cyclic enones/enoates at room temperature after convenient reaction times.
• KR102072378
  申请人：——

  公开号：——

  公开（公告）日：——
• Anti-inflammatory effects of an optimized PPAR-γ agonist via NF-κB pathway inhibition
  作者：Zhiran Ju、Mingzhi Su、Jongki Hong、Eun La Kim、Jee H. Jung

  DOI：10.1016/j.bioorg.2020.103611

  日期：2020.3

  In our previous study, a PPAR-gamma agonist (+)-(R,E)-6a1 was elaborated as an anti-inflammatory lead. However, in silico analysis showed that (+ )-(R,E)-6a1 lacks key hydrogen bonding with Tyr(473) of PPAR-gamma LBD (ligand binding domain). To facilitate additional hydrogen bonding with Tyr(473), a more polar head group was introduced to the structure of (+)-(R,E)-6a1, and we also attempted to synthesize enzymatically stable derivatives. Of the synthetic derivatives, compound (+)-(R,E)-5f showed highest PPAR-gamma transcriptional activity and reasonable metabolic stability. Compound (+)-(R,E)-5f suppressed the expression of pro-inflammatory mediators such as inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and tumor necrosis factor-alpha(TNF-alpha). Reduction of nitric oxide (NO), and ROS was also observed. Compound ( + )-(R,E)-5f was found to suppress the NF-kappa B pathway by inhibiting phosphorylation of IKK (I kappa B kinase), and this may lead to subsequent inhibition of I kappa B alpha (inhibitor of NF-kappa Ba) phosphorylation and inhibition of NF-kappa B activation. These results indicate that (+)-(R,E)-5f exerts anti-inflammatory activity via NF-KB pathway inhibition, and may serve as a potential anti-inflammatory lead.