tert-butyl 2-oxo-4-(p-tolyl)butanoate | 147485-06-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl 2-oxo-4-(p-tolyl)butanoate
• 英文别名: tert-butyl 2-oxo-4-(4-methylphenyl)butyrate；t-Butyl 2-oxo-4-(4-methylphenyl)-butanoate；tert-butyl 4-(4-methylphenyl)-2-oxobutanoate
• CAS: 147485-06-1
• 化学式: C₁₅H₂₀O₃
• 分子量: 248.322
• InChiKey: PAGFOTUDGKPNMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-oxo-4-(p-tolyl)butanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到4-(p-methylphenyl)-2-oxobutanoic acid
  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-甲基苯乙基溴 在 碘 、 magnesium 作用下， 以 乙醚 为溶剂， 反应 3.0h， 生成 tert-butyl 2-oxo-4-(p-tolyl)butanoate
  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

文献信息

• Dynamics in Catalytic Asymmetric Diastereoconvergent (3 + 2) Cycloadditions with Isomerizable Nitrones and α-Keto Ester Enolates
  作者：Tetsuya Ezawa、Yoshihiro Sohtome、Daisuke Hashizume、Masaya Adachi、Mai Akakabe、Hiroyuki Koshino、Mikiko Sodeoka

  DOI：10.1021/jacs.1c02833

  日期：2021.6.23

  Reaction design in asymmetric catalysis has traditionally been predicated on a structurally robust scaffold in both substrates and catalysts, to reduce the number of possible diastereomeric transition states. Herein, we present the stereochemical dynamics in the Ni(II)-catalyzed diastereoconvergent (3 + 2) cycloadditions of isomerizable nitrile-conjugated nitrones with α-keto ester enolates. Even in

  传统上，不对称催化中的反应设计基于底物和催化剂中结构坚固的支架，以减少可能的非对映异构过渡态的数量。在此，我们展示了 Ni(II) 催化的非对映会聚 (3 + 2) 环加成反应中的可异构化腈共轭硝酮与 α-酮酯烯醇化物的立体化学动力学。即使在存在多个平衡物种的情况下，催化协议也显示出广泛的底物范围，以访问一系列带有相邻立体中心的含 CN 构建块，具有高对映选择性和非对映选择性。我们的计算研究表明，在去质子化过程中形成 ( Z )-Ni-烯醇化物的过程中控制了对映选择性，而独特的合成 添加主要由硝酮和配体之间的弱非共价键相互作用控制。
• A Highly Diastereo- and Enantioselective Reaction for Constructing Functionalized Cyclohexanes: Six Contiguous Stereocenters in One Step
  作者：Dengjian Shi、Yinjun Xie、Han Zhou、Chungu Xia、Hanmin Huang

  DOI：10.1002/anie.201107495

  日期：2012.1.27

  Just mix to get six: Six contiguous stereocenters, including one quaternary stereocenter, and three CC bonds are created by a new copper‐catalyzed tandem reaction (see scheme). Rigid chiral diamine ligands enabled this asymmetric tandem reaction to proceed with excellent stereoselectivity (complete diastereoselectivity and high enantioselectivity) and high yield under mild reaction conditions.

  只需混合即可得到六个：六价连续的立体中心（包括一个四级立体中心）和三个CC键是通过新的铜催化串联反应生成的（请参见方案）。刚性手性二胺配体使这种不对称串联反应能够在温和的反应条件下以优异的立体选择性（完全的非对映选择性和高对映选择性）和高收率进行。
• Diastereo- and enantioselective conjugate addition of α-keto esters to nitroalkenes: Complete switch in the enantioselectivity by tuning the metal center or rigidity of the ligand
  作者：Xiangning Chen、Han Zhou、Hanmin Huang

  DOI：10.1016/s1872-2067(14)60199-6

  日期：2015.1

  been developed to control the dual enantioselectivity of the conjugate addition of α-keto esters to nitroalkenes. The use of the chiral diamine (1 S ,1’ S )-1,1′-biisoindoline as a chiral ligand with either (Cu(OAc) 2 ·H 2 O or Ni(OAc) 2 ·4H 2 O as the catalyst provide facile access to the respective enantiomers resulting from the conjugate addition reaction with high levels of enantioselectivity (94%

  摘要 已经开发了一系列有效的催化系统来控制 α-酮酯与硝基烯烃共轭加成的双重对映选择性。使用手性二胺 (1 S ,1' S )-1,1'-双异二氢吲哚作为手性配体，以 (Cu(OAc) 2 ·H 2 O 或 Ni(OAc) 2 ·4H 2 O 为催化剂)以高水平的对映选择性（94% ee vs 93% ee）轻松获得由共轭加成反应产生的各个对映异构体。此外，使用 Cu(OAc) 2 ·H 2 O 作为金属中心允许对映选择性通过调节手性二胺配体的刚性（94% ee vs 94% ee）来切换共轭加成反应。
• Catalytic Asymmetric Mono-Fluorination of α-Keto Esters: Synthesis of Optically Active β-Fluoro-α-Hydroxy and β-Fluoro-α-Amino Acid Derivatives
  作者：Shoko Suzuki、Yuki Kitamura、Sylvain Lectard、Yoshitaka Hamashima、Mikiko Sodeoka

  DOI：10.1002/anie.201201303

  日期：2012.5.7

  Enantioselective mono‐fluorination of α‐keto esters was achieved using a mildly basic palladium μ‐hydroxo complex as catalyst. Subsequent one‐pot reduction afforded optically active β‐fluoro‐α‐hydroxy esters. These compounds were then converted into β‐fluoro‐α‐amino esters, which are potentially useful in medicinal chemistry research.

  α-酮酸酯的对映选择性单氟化是通过使用温和碱性的钯μ-羟基络合物作为催化剂来实现的。随后的一锅还原得到旋光的β-氟-α-羟基酯。然后将这些化合物转化为β-氟-α-氨基酯，这可能在药物化学研究中有用。
• New Two-Step Synthesis of Azulene-1-carboxylic Esters Using Lithium Trimethylsilyldiazomethane
  作者：Toyohiko Aoyama、Yoshiyuki Hari、Shunkichi Tanaka、Yasuta Takuma

  DOI：10.1055/s-2003-42064

  日期：——

  hane successfully reacted with various ethyl or tert-butyl 4-aryl-2-oxobutanoates to yield 2,3-dihydroazulene-1-carboxylic esters via alkylidene carbene intermediates, and the resulting 2,3-dihydroazulenes were easily converted to the corresponding azulene-1-carboxylic esters by oxidation with chemical manganese dioxide.

  三甲基甲硅烷基重氮甲烷锂与各种乙基或叔丁基 4-芳基-2-氧代丁酸酯成功反应，通过亚烷基卡宾中间体生成 2,3-二氢茚-1-羧酸酯，所得 2,3-二氢茚烯很容易转化为相应的茚-1-羧酸酯通过化学二氧化锰氧化。