(2E,6E)-2,6-bis(2-fluorobenzylidene)cyclohexanone | 1158188-80-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (2E,6E)-2,6-bis(2-fluorobenzylidene)cyclohexanone
• 英文别名: 2,6-Bis(2-Fluorobenzylidene)Cyclohexanone；(2E,6E)-2,6-bis[(2-fluorophenyl)methylidene]cyclohexan-1-one
• CAS: 1158188-80-7
• 化学式: C₂₀H₁₆F₂O
• 分子量: 310.343
• InChiKey: WIDDWATUDMOWCU-UNZYHPAISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2E,6E)-2,6-bis(2-fluorobenzylidene)cyclohexanone 、 [(苯基甲亚基)氨基]乙酸甲酯 在 (S)-N-((S)-(4-(tert-butyl)phenyl)((1R,4S)-4,5-dimethyl-3,6-diphenyl-1-phosphabicyclo[2.2.1]hepta-2,5-dien-2-yl)methyl)-2-methylpropane-2-sulfinamide 、 potassium carbonate 、 双三氟甲烷磺酰亚胺银盐 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以93%的产率得到methyl (1R,3R,4S,5S)-7-((E)-2-fluorobenzylidene)-4-(2-fluorophenyl)-6-oxo-1-phenyl-2-azaspiro[4.5]decane-3-carboxylate
  参考文献：
  名称：

  Ag / P-Stereogenic膦催化的对映选择性1,3-偶极环加成反应：一种光学活性吡咯烷酮的方法

  摘要：

  报道了Ag / P-立体异构的膦复合物催化的偶氮甲亚胺的1,3-偶极环加成与缺电子的烯烃。在该反应中，获得了具有螺四元立体构型中心的高度官能化的吡咯啉，收率好（高达99％），非对映体（高达> 20：1 dr）和对映体选择性（高达> 99％ee） 。加合物的手性主要受P-立体生成的膦所控制。

  DOI：

  10.1021/acs.orglett.9b00926
• 作为产物：
  描述：

  环己酮 、 2-氟苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 48.0h， 生成 (2E,6E)-2,6-bis(2-fluorobenzylidene)cyclohexanone
  参考文献：
  名称：

  Curcumin-like diarylpentanoid analogues as melanogenesis inhibitors

  摘要：

  对47种合成的姜黄素样二芳基戊烷类类似物进行了抗黑色素生成筛选，结果显示其中一些对B16黑色素瘤细胞的黑色素生成具有强抑制作用。这些作用主要被认为是通过抑制酪氨酸酶活性、抑制酪氨酸酶表达和降解黑色素色素实现的。还讨论了那些抑制黑色素生成和酪氨酸酶活性的姜黄素样二芳基戊烷类类似物的结构-活性关系。在测试的化合物中，（2E,6E）-2,6-双（2,5-二甲氧基苄叉）环己酮显示了最强的抗黑色素生成效果，其机制被认为是在B16黑色素瘤细胞中降解黑色素色素，既不影响酪氨酸酶活性也不影响酪氨酸酶表达。

  DOI：

  10.1007/s11418-011-0568-0

文献信息

• Inhibitor of CBP Histone Acetyltransferase Downregulates p53 Activation and Facilitates Methylation at Lysine 27 on Histone H3
  作者：Adam Vincek、Jigneshkumar Patel、Anbalagan Jaganathan、Antonia Green、Valerie Pierre-Louis、Vimal Arora、Jill Rehmann、Mihaly Mezei、Ming-Ming Zhou、Michael Ohlmeyer、Shiraz Mujtaba

  DOI：10.3390/molecules23081930

  日期：——

  small molecules with potential to downregulate the activation of p53 could minimize pathology emerging from anticancer therapies. Acetylation of p53 by the histone acetyltransferase (HAT) domain is the hallmark of coactivator CREB-binding protein (CBP) epigenetic function. During genotoxic stress, CBP HAT-mediated acetylation is essential for the activation of p53 to transcriptionally govern target genes

  肿瘤抑制因子 p53 导向的细胞凋亡会引发正常细胞的丢失，从而导致抗癌疗法的副作用。因此，具有下调 p53 激活潜力的小分子可以最大限度地减少抗癌治疗中出现的病理。组蛋白乙酰转移酶 (HAT) 域对 p53 的乙酰化是共激活因子 CREB ​​结合蛋白 (CBP) 表观遗传功能的标志。在基因毒性应激期间，CBP HAT 介导的乙酰化对于激活 p53 以转录控制靶基因（控制细胞反应）至关重要。在这里，我们提出了一种小分子 NiCur，它可以阻断 CBP HAT 的活性并在基因毒性应激时下调 p53 的激活。计算模型显示 NiCur 停靠在 CBP HAT 的活性位点。在 CDKN1A 启动子上，NiCur 减少了 p53 和 RNA 聚合酶 II 的募集以及组蛋白 H3 的乙酰化水平。具体来说，NiCur 降低组蛋白 H3 上赖氨酸 27 的乙酰化水平，这同时增加了赖氨酸 27 的三甲基化水平。
• Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents
  作者：Guang Liang、Lili Shao、Yi Wang、Chengguang Zhao、Yanhui Chu、Jian Xiao、Yu Zhao、Xiaokun Li、Shulin Yang

  DOI：10.1016/j.bmc.2008.10.044

  日期：2009.3

  Curcumin has a surprisingly wide range of chemo-preventive and chemo-therapeutic activities and is under investigation for the treatment of various human cancers. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Although a number of synthetic modi. cations of curcumin have been studied intensively in order to develop a molecule with enhanced bioactivities, few synthetic studies were done for the improvement of pharmacokinetic profiles. In the present study, a series of mono-carbonyl analogues of curcumin were designed and synthesized by deleting the reactive beta-diketone moiety, which was considered to be responsible for the pharmacokinetic limitation of curcumin. The results of the in vitro stability studies and in vivo pharmacokinetic studies indicated that the stability of these mono-carbonyl analogues was greatly enhanced in vitro and their pharmacokinetic profiles were also significantly improved in vivo. Furthermore, the cytotoxic activities of mono-carbonyl analogues were evaluated in seven different tumor cell lines by MTT assay and the structure-activity relation (SAR) was discussed and concluded. The results suggest that the five-carbon linker-containing analogues of curcumin may be favorable for the curcumin-based drug development both pharmacokinetically and pharmacologically. (C) 2009 Published by Elsevier Ltd.
• Ag/P-Stereogenic Phosphine-Catalyzed Enantioselective 1,3-Dipolar Cycloadditions: A Method to Optically Active Pyrrolidines
  作者：Mengna Zhi、Zhenjie Gan、Rong Ma、Hao Cui、Er-Qing Li、Zheng Duan、François Mathey

  DOI：10.1021/acs.orglett.9b00926

  日期：2019.5.3

  A Ag/P-stereogenic phosphine-complex-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with electron-deficient olefins is reported. In this reaction, highly functionalized pyrrolines with a spiro-quaternary stereogenic center were obtained in good yields (up to 99%) with excellent levels of diastereo- (up to >20:1 dr) and enantioselectivities (up to >99% ee). The chirality of adducts was controlled

  报道了Ag / P-立体异构的膦复合物催化的偶氮甲亚胺的1,3-偶极环加成与缺电子的烯烃。在该反应中，获得了具有螺四元立体构型中心的高度官能化的吡咯啉，收率好（高达99％），非对映体（高达> 20：1 dr）和对映体选择性（高达> 99％ee） 。加合物的手性主要受P-立体生成的膦所控制。
• Curcumin-like diarylpentanoid analogues as melanogenesis inhibitors
  作者：Takahiro Hosoya、Asami Nakata、Fumie Yamasaki、Faridah Abas、Khozirah Shaari、Nordin Hj Lajis、Hiroshi Morita

  DOI：10.1007/s11418-011-0568-0

  日期：2012.1

  Anti-melanogenesis screening of 47 synthesized curcumin-like diarylpentanoid analogues was performed to show that some had a potent inhibitory effect on the melanogenesis in B16 melanoma cells. Their actions were considered to be mostly due to tyrosinase inhibition, tyrosinase expression inhibition, and melanin pigment degradation. The structure–activity relationships of those curcumin-like diarylpentanoid analogues which inhibited the melanogenesis and tyrosinase activity were also discussed. Of those compounds assayed, (2E,6E)-2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone showed the most potent anti-melanogenesis effect, the mechanism of which is considered to be the degradation of the melanin pigment in B16 melanoma cells, affecting neither the tyrosinase activity nor tyrosinase expression.

  对47种合成的姜黄素样二芳基戊烷类类似物进行了抗黑色素生成筛选，结果显示其中一些对B16黑色素瘤细胞的黑色素生成具有强抑制作用。这些作用主要被认为是通过抑制酪氨酸酶活性、抑制酪氨酸酶表达和降解黑色素色素实现的。还讨论了那些抑制黑色素生成和酪氨酸酶活性的姜黄素样二芳基戊烷类类似物的结构-活性关系。在测试的化合物中，（2E,6E）-2,6-双（2,5-二甲氧基苄叉）环己酮显示了最强的抗黑色素生成效果，其机制被认为是在B16黑色素瘤细胞中降解黑色素色素，既不影响酪氨酸酶活性也不影响酪氨酸酶表达。