potassium 4-(4-chlorophenyl)-2-oxo-but-3-enoate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: potassium 4-(4-chlorophenyl)-2-oxo-but-3-enoate
• 英文别名: potassium;(E)-4-(4-chlorophenyl)-2-oxobut-3-enoate
• 化学式: C₁₀H₆ClO₃*K
• 分子量: 248.707
• InChiKey: OSEMXBBUFWNZHP-ZIKNSQGESA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.32
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  potassium 4-(4-chlorophenyl)-2-oxo-but-3-enoate 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (E)-4-(4-chlorophenyl)-2-oxo-N-phenethylbut-3-enamide
  参考文献：
  名称：

  Structure–Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family

  摘要：

  The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists of five members, which are involved in the Ca2+-independent production of N-acylphosphatidylethanolamines (NAPEs). NAPEs are lipid precursors for bioactive N-acylethanolamines (NAEs) that are involved in various physiological processes such as food intake, pain, inflammation, stress, and anxiety. Recently, we identified alpha-ketoamides as the first pan-active PLAAT inhibitor scaffold that reduced arachidonic acid levels in PLAAT3-overexpressing U2OS cells and in HepG2 cells. Here, we report the structure-activity relationships of the alpha-ketoamide series using activity-based protein profiling. This led to the identification of LEI-301, a nanomolar potent inhibitor for the PLAAT family members. LEI-301 reduced the NAE levels, including anandamide, in cells overexpressing PLAAT2 or PLAAT5. Collectively, LEI-301 may help to dissect the physiological role of the PLAATs.

  DOI：

  10.1021/acs.jmedchem.0c00522
• 作为产物：
  描述：

  4-氯苯甲醛 、 丙酮酸 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 生成 potassium 4-(4-chlorophenyl)-2-oxo-but-3-enoate
  参考文献：
  名称：

  2-羟基-3-烯酸钾可作为NHC催化的不对称反应中α，β-不饱和醛的有效且多用途的替代物

  摘要：

  2-羟基-3-烯酸钾很容易大规模制备并易于储存，已被发现是NHC催化的不对称反应中α，β-不饱和醛的有效且多用途的替代物。这些易处理的固体盐在手性N-杂环卡宾与LiCl的共同作用下可以释放出CO 2，然后通过同烯酸酯和α，β-不饱和酰基偶氮中间体发生不对称反应。反应具有高对映选择性的广泛的底物范围。

  DOI：

  10.1002/adsc.201701413

文献信息

• Bimetallic Catalytic Asymmetric Tandem Reaction of β‐Alkynyl Ketones to Synthesize 6,6‐Spiroketals
  作者：Shulin Ge、Weidi Cao、Tengfei Kang、Bowen Hu、Hang Zhang、Zhishan Su、Xiaohua Liu、Xiaoming Feng

  DOI：10.1002/anie.201812842

  日期：2019.3.18

  The enantioselective tandem reaction of β,γ‐unsaturated α‐ketoesters with β‐alkynyl ketones was realized by a bimetallic catalytic system of achiral AuΙΙΙ salt and chiral N,N′‐dioxide‐MgΙΙ complex. The cycloisomerization of β‐alkynyl ketone and asymmetric intermolecular [4+2] cycloaddition with β,γ‐unsaturated α‐ketoesters subsequently occurred, providing an efficient and straightforward access to

  β的对映选择性串联反应，具有β -炔基酮γ不饱和α酮酯是由非手性Au的双金属催化剂体系实现ΙΙΙ盐和手性Ñ，Ñ '二氧化物-镁ΙΙ复杂。随后发生了β-炔基酮的环异构化和不对称分子间[4 + 2]与β，γ-不饱和α-酮酸酯的加成反应，可高效，直接地获得手性多功能6,6-螺缩酮，产率高达97％，94 ％ee和> 19/1 dr此外，基于控制实验的结果，提出了一个催化循环。
• Facile synthesis of substituted diaryl sulfones <i>via</i> a [3 + 3] benzannulation strategy
  作者：Xiang-zheng Tang、Lang Tong、Hua-ju Liang、Jie Liang、Yong Zou、Xue-jing Zhang、Ming Yan、Albert S. C. Chan

  DOI：10.1039/c8ob00662h

  日期：——

  base-mediated [3 + 3] benzannulation strategy for the conversion of 1,3-bis(sulfonyl)propenes and β,γ-unsaturated α-ketoesters to diaryl sulfones has been developed. This method provides facile, metal-free and efficient access to highly substituted diaryl sulfones in good to excellent yields. In addition, the sulfonyl group could be easily removed or converted to other functional groups via an organostannane

  已开发出一种由碱介导的[3 + 3]苯环芳构化策略，可将1,3-双（磺酰基）丙烯和β，γ-不饱和α-酮酸酯转化为二芳基砜。该方法可以轻松，无金属且高效地获得高取代的二芳基砜，且收率良好。另外，磺酰基可通过有机锡烷中间体容易地除去或转化为其他官能团。
• Synthesis of Chiral Bispirotetrahydrofuran Oxindoles by Cooperative Bimetallic-Catalyzed Asymmetric Cascade Reaction
  作者：Meng-Meng Liu、Xiao-Chao Yang、Yuan-Zhao Hua、Jun-Biao Chang、Min-Can Wang

  DOI：10.1021/acs.orglett.9b00386

  日期：2019.4.5

  Under mild conditions, a broad range of bispirotetrahydrofuran oxindoles have been synthesized with excellent stereoselectivities through the cascade Michael/hemiketalization/Friedel–Crafts reaction of β,γ-unsaturated α-ketoamide and 2-hydroxy-1-indanone. The reaction can be performed on a gram scale with low catalyst loading (2 mol %) without impacting its efficiency.

  通过协同双核锌-AzePhenol催化剂描述了一种对映选择性构建双螺四氢呋喃羟吲哚的新的有效途径。在温和的条件下，通过β，γ-不饱和α-酮酰胺和2-羟基-1-茚满酮的级联迈克尔/半缩酮化/弗里德-克拉夫茨反应，合成了多种具有优良立体选择性的双螺四氢呋喃恶吲哚。该反应可以以克级进行，催化剂负载量低（2mol％），而不会影响其效率。
• Potassium 2-oxo-3-enoates as Effective and Versatile Surrogates for α, β-Unsaturated Aldehydes in NHC-Catalyzed Asymmetric Reactions
  作者：Yaru Gao、Yafei Ma、Chen Xu、Lin Li、Tianjian Yang、Guoqing Sima、Zhenqian Fu、Wei Huang

  DOI：10.1002/adsc.201701413

  日期：2018.2.1

  to be effective and versatile surrogates for α,β‐unsaturated aldehydes in NHC‐catalyzed asymmetric reactions. Promoted by chiral N‐heterocyclic carbenes combined with LiCl, these easy‐to‐handle solid salts could release of CO2 and then undergo asymmetric reactions via homoenolate and α, β‐unsaturated acyl azolium intermediate. The reactions have broad substrate scopes with high enantioselectivities.

  2-羟基-3-烯酸钾很容易大规模制备并易于储存，已被发现是NHC催化的不对称反应中α，β-不饱和醛的有效且多用途的替代物。这些易处理的固体盐在手性N-杂环卡宾与LiCl的共同作用下可以释放出CO 2，然后通过同烯酸酯和α，β-不饱和酰基偶氮中间体发生不对称反应。反应具有高对映选择性的广泛的底物范围。
• Diaryl Dihydropyrazole-3-carboxamides with Significant In Vivo Antiobesity Activity Related to CB1 Receptor Antagonism:  Synthesis, Biological Evaluation, and Molecular Modeling in the Homology Model
  作者：Brijesh Kumar Srivastava,*、Amit Joharapurkar、Saurin Raval、Jayendra Z. Patel、Rina Soni、Preeti Raval、Archana Gite、Amitgiri Goswami、Nisha Sadhwani、Neha Gandhi、Harilal Patel、Bhupendra Mishra、Manish Solanki、Bipin Pandey、Mukul R. Jain、Pankaj R. Patel

  DOI：10.1021/jm061490u

  日期：2007.11.1

  A number of analogues of diaryl dihydropyrazole-3-carboxamides have been synthesized. Their activities were evaluated for appetite suppression and body weight reduction in animal models. Depending on the chemical modification of the selected dihydropyrazole scaffold, the lead compounds-the bisulfate salt,of (+/-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 26 and the bisulfate salt of (-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole3-carboxylic acid morpholin-4-ylamide 30-showed significant body weight reduction in vivo, which is attributed to their CB1 antagonistic activity and exhibited a favorable pharmacokinetic profile. The molecular modeling studies also showed interactions of two isomers of (+/-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)4,5-dihydro- 1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 9 with CB I receptor in the homology model similar to those of N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxarnide (rimonabant) 1 and 4S-(-)-3-(4-chlorophenyl)-N-methyl-N'-[(4-chlorophenyl)-sulfonyl]-4-pheny1-4,5-dihydro-1H-pyrazole-1-carboxamidine (SLV-319) 2.