2-(2-methylbenzyl)-3-oxo-butyric acid methyl ester | 1203476-26-9

• 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: 2-(2-methylbenzyl)-3-oxo-butyric acid methyl ester
• CAS: 1203476-26-9
• 化学式: C₁₃H₁₆O₃
• 分子量: 220.268
• InChiKey: TWRRJHFQHUYZDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.92
• 重原子数：
  16.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  43.37
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-(2-methylbenzyl)-3-oxo-butyric acid methyl ester 在 1,1,1-trifluoro-N-((trifluoromethyl)sulfonyl)methanesulfonamide compound with (S)-3,3-bis(3,5-dimethylphenyl)-1-phenyltetrahydro-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborole (1:1) 、 4-乙酰氨基苯磺酰叠氮 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (S)-1-methoxy-1-oxo-3-(o-tolyl)propan-2-yl benzoate
  参考文献：
  名称：

  重氮杂酸酯与手性恶唑硼烷鎓离子活化的羧酸的催化对映选择性质子化/亲核加成反应

  摘要：

  引入了一种新的手性布朗斯台德酸，其衍生自羧酸和手性恶唑硼烷鎓离子（COBI）作为活化剂。该酸已成功地用作重氮酸酯与羧酸的高度对映选择性质子化/亲核加成的催化剂。

  DOI：

  10.1002/anie.201612655
• 作为产物：
  描述：

  乙酰乙酸甲酯 、 2-甲基苄溴 在 potassium tert-butylate 、 叔丁醇 作用下， 以 四氢呋喃 为溶剂， 反应 0.83h， 以65%的产率得到2-(2-methylbenzyl)-3-oxo-butyric acid methyl ester
  参考文献：
  名称：

  Cyclization of Arylacetoacetates to Indene and Dihydronaphthalene Derivatives in Strong Acids. Evidence for Involvement of Further Protonation of O,O-Diprotonated β-Ketoester, Leading to Enhancement of Cyclization

  摘要：

  The chemical features, such as substrate stability, product distribution, and substrate generality, and the reaction mechanism of Bronsted superacid-catalyzed cyclization reactions of aromatic ring-containing acetoacetates (beta-ketoesters) were examined in detail. While two types of carbonyl cyclization are possible, i.e., keto cyclization and ester cyclization, the former was found to take place exclusively. The reaction constitutes an efficient method to synthesize indene and 3,4-dihydronapthalene derivatives. Acid-base titration monitored with C-13 NMR spectroscopy showed that the acetoacetates are fully O-1,O-3-diprotonated at H-0 = -11. While the five-membered ring cyclization of the arylacetoacetates proceeded slowly at H-0 = -11, a linear increase in the rate of the cyclization was found with increasing acidity in the high acidity region of H-0 = -11.8 to -13.3. Therefore, the O-1,O-3-diprotonated acetoacetates exhibited some cyclizing reactivity, but they are not the reactive intermediates responsible for the acceleration of the cyclization in the high acidity region. The reactive cationic species might be formed by further protonation (or protosolvation) of the O-1,O-3-diprotonated acetoacetates; i.e., they may be tricationic species. Thermochemical data on the acid-catalyzed cyclization of the arylacetoacetates showed that the activation energy is decreased significantly as compared with that of the related acid-catalyzed cyclization reaction of a compound bearing a single functional group, such as a ketone. These findings indicate that intervention of the trication contributes to the activation of the cyclization of arylacetoacetates in strong acid, and the electron-withdrawing nature of the O-protonated ester functionality significantly increases the electrophilicity of the ketone moiety.

  DOI：

  10.1021/ja908749u

文献信息

• Desymmetrizing Asymmetric Ring Expansion of Cyclohexanones with α-Diazoacetates Catalyzed by Chiral Aluminum Lewis Acid
  作者：Takuya Hashimoto、Yuki Naganawa、Keiji Maruoka

  DOI：10.1021/ja202070j

  日期：2011.6.15

  in a 2:1 ratio was found to promote novel catalytic asymmetric ring expansion of cyclohexanone with α-substituted α-diazoacetates to give seven-membered rings with an all-carbon quaternary center. Application of this strategy to 4-substituted cyclohexanones opened up a novel way for the catalytic desymmetrizing asymmetric construction of cycloheptanones bearing remote α,δ-chiral centers.

  由 Me(3)Al 和 3,3'-双(三甲基甲硅烷基)-BINOL 以 2:1 的比例组成的手性铝路易斯酸催化剂被发现可促进环己酮与 α-取代的 α-重氮乙酸酯的新型催化不对称扩环，得到具有全碳四元中心的七元环。将该策略应用于 4-取代环己酮为带有远程 α,δ-手性中心的环庚酮的催化去对称不对称结构开辟了一条新途径。
• Design, Synthesis, and Structure‐Activity Relationship Study of Pyrazolones as Potent Inhibitors of Pancreatic Lipase
  作者：Jing Zhang、Yang Yang、Xing‐Kai Qian、Pei‐Fang Song、Yi‐Shu Zhao、Xiao‐Qing Guan、Li‐Wei Zou、Xiaoze Bao、Hong Wang

  DOI：10.1002/cmdc.202000850

  日期：2021.5.18

  mixed-competitive inhibitor of PL (IC50=0.30 μM). In addition, P32 displayed some selectivity over other known serine hydrolases. A molecular docking study for P32 demonstrated that the inhibitory activity of P32 towards PL could be attributed to the π-π interactions of 2-naphthyl unit (R1) and hydrophobic interactions of phenyl moiety (R3) with the active site of PL. Thus, P32 could serve as promising lead

  胰脂肪酶（PL）是预防和治疗肥胖的关键靶点，在膳食脂肪的水解和吸收中起着至关重要的作用。本研究合成了一系列吡唑啉酮类药物，并以4-甲基伞形酮油酸酯（4-MUO）作为PL的光学底物测定了它们对PL的抑制作用。这些吡唑啉酮类的综合构效关系分析使我们设计并合成了一种新型化合物P32 (5-(naphthalen-2-yl)-2-phenyl-4-(thiophen-2-ylmethyl)-2,4-dihydro- 3 H -pyrazol-3-one) 作为 PL 的有效混合竞争性抑制剂 (IC 50 =0.30 μM)。此外，P32对其他已知的丝氨酸水解酶具有一定的选择性。P32的分子对接研究证明P32对PL的抑制活性可归因于2-萘基单元（R 1）的π-π相互作用和苯基部分（R 3）与PL活性位点的疏水相互作用。因此，P32可以作为有前途的先导化合物，用于开发更有效和选择性的吡唑啉酮类 PL 抑制剂，用于生物医学应用。
• Discovery of pyrazolones as novel carboxylesterase 2 inhibitors that potently inhibit the adipogenesis in cells
  作者：Xing-Kai Qian、Jing Zhang、Pei-Fang Song、Yi-Su Zhao、Hong-Ying Ma、Qiang Jin、Dan-Dan Wang、Xiao-Qing Guan、Shi-Yang Li、XiaoZe Bao、Li-Wei Zou

  DOI：10.1016/j.bmc.2021.116187

  日期：2021.6

  kinetic study demonstrated that compound 27 inhibited the hydrolysis of CES2-fluorescein diacetate (FD) through non-competitive inhibition. In addition, the molecular docking showed that the core of pyrazolone, the cyclohexane moiety, 4-methylbenzyl and 4-methylphenyl groups in compound 27 all played important roles with the amino acid residues of CSE2. Also, compound 27 could inhibit adipocyte adipogenesis

  羧酸酯酶 2 (CES2) 是羧酸酯酶家族中最重要的 I 期药物代谢酶之一。它在口服酯类前药的生物利用度和一些抗癌药物如伊立替康 (CPT11) 和卡培他滨的治疗效果中起着至关重要的作用。除了众所周知的 CES2 在异生物质代谢中的作用外，该酶还参与内源性代谢和脂质的产生。在这项研究中，我们合成了一系列吡唑啉酮并在体外测定了它们对 CES2 的抑制作用。这些吡唑啉酮的构效关系分析表明，4-甲基苯基单元（R 1）、4-甲基苄基（R 2）和环己基（R 3) 部分有利于 CES2 抑制。根据这些 SARs 结果，设计并合成了1-cyclohexyl-4-(4-methylbenzyl)-3-p-tolyl-1H-pyrazol-5(4H)-one ( 27 )。进一步的研究表明，化合物27表现出更强的CES2抑制活性，IC 50值更低（0.13 μM）。抑制动力学研究表明，化合物27通过非竞争性抑制来抑制