2-(4-bromophenoxy)-2-methylbutanoic acid | 1229447-55-5

• 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-(4-bromophenoxy)-2-methylbutanoic acid
• 英文别名: (2R)-2-(4-bromophenoxy)-2-methylbutanoic acid
• CAS: 1229447-55-5
• 化学式: C₁₁H₁₃BrO₃
• 分子量: 273.126
• InChiKey: JNWUSQKIABEOIC-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甲醇 、 2-(4-bromophenoxy)-2-methylbutanoic acid 在 硫酸 作用下， 反应 3.0h， 以94%的产率得到(+)-R-methyl 2-(4-bromo-phenoxy)-2-methylbutanoate
  参考文献：
  名称：

  Structural Insight into Peroxisome Proliferator-Activated Receptor γ Binding of Two Ureidofibrate-Like Enantiomers by Molecular Dynamics, Cofactor Interaction Analysis, and Site-Directed Mutagenesis

  摘要：

  Molecular dynamics simulations were performed on two ureidofibrate-like enantiomers to gain insight into their different potency and efficacy against PPAR gamma. The partial agonism of the Senantiomer seems to be due to its capability to stabilize different regions of the receptor allowing the interaction with both coactivators and corepressors as shown by fluorescence resonance energy transfer (FRET) assays. The recruitment of the corepressor N-CoR1 by the S enantiomer on two different responsive elements of PPAR gamma regulated promoters was confirmed by chromatin immunoprecipitation assays. Cell-based transcription assays show that PPAR gamma coactivator 1 alpha (PGC-1 alpha) and cAMP response element binding protein-binding protein (CBP) enhance the basal and ligand-stimulated receptor activity acting as coactivators of PPAR gamma, whereas the receptor interacting protein 140 (RIP140) and the nuclear corepressor 1 (N-CoR1) repress the transcriptional activity of PPAR gamma. We also tested the importance of the residue Q286 on the transcriptional activity of the receptor by site-directed mutagenesis and confirmed its key role in the stabilization of helix 12. Molecular modeling studies were performed to provide a molecular explanation for the different behavior of the mutants.

  DOI：

  10.1021/jm9013899
• 作为产物：
  描述：

  t-butyl 2-(4-bromophenoxy)-2-methyl-3-oxobutanoate 在 吡啶 、 sodium tetrahydroborate 、 tetrabutylammonium borohydride 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 9.17h， 生成 2-(4-bromophenoxy)-2-methylbutanoic acid
  参考文献：
  名称：

  在叔立体碳上用酚类合成威廉姆森醚：β-酮基酯的形式对映选择性苯氧基化

  摘要：

  首次描述了α-芳氧基-β-酮酸酯的对映选择性形成。路易斯酸催化β-酮酯的对映选择性氯化，随后与酚进行S N 2反应，生成ee高达96％的α-芳氧基-β-酮酯 。还发现α-氯-β-酮基酯的Favorskii重排产生1,2-二酯，其对映体纯度略有降低。

  DOI：

  10.1002/chem.201502042

文献信息

• 10.1016/j.ejmech.2024.116567
  作者：Laghezza, Antonio、Cerchia, Carmen、Genovese, Massimo、Montanari, Roberta、Capelli, Davide、Wackerlig, Judith、Simic, Stefan、Falbo, Emanuele、Pecora, Lucia、Leuci, Rosalba、Brunetti, Leonardo、Piemontese, Luca、Tortorella, Paolo、Biswas, Abanish、Singh, Ravi Pratap、Tambe, Suhas、Sudeep、Pattnaik, Ashok Kumar、Jayaprakash, Venkatesan、Paoli, Paolo、Lavecchia, Antonio、Loiodice, Fulvio

  DOI：10.1016/j.ejmech.2024.116567

  日期：——

  New analogs of the PPAR pan agonist AL29-26 encompassed ligand ()- showing potent activation of PPARα and -γ subtypes as a partial agonist. In vitro experiments and docking studies in the presence of PPAR antagonists were performed to help interpretation of biological data and investigate the main interactions at the binding sites. Further in vitro experiments showed that ()- induced anti-steatotic

  PPAR 全激动剂 AL29-26 的新类似物包含配体 ()-，作为部分激动剂，可有效激活 PPARα 和 -γ 亚型。在 PPAR 拮抗剂存在的情况下进行体外实验和对接研究，以帮助解释生物学数据并研究结合位点的主要相互作用。进一步的体外实验表明，()-诱导抗脂肪变性作用并增强葡萄糖摄取。后一种效应可能部分归因于线粒体丙酮酸载体的显着抑制，表明 ()- 也通过不依赖胰岛素​​的机​​制发挥作用。体内实验表明，该化合物可降低糖尿病小鼠模型的血糖和血脂水平，且对骨骼、肾脏和肝脏没有毒性。据我们所知，这是 PPARα/γ 双重部分激动剂的第一个例子，显示了这些联合作用，因此，代表了治疗血脂异常 2 型糖尿病新药的潜在先导。
• Williamson Ether Synthesis with Phenols at a Tertiary Stereogenic Carbon: Formal Enantioselective Phenoxylation of β‐Keto Esters
  作者：Kazutaka Shibatomi、Manato Kotozaki、Nozomi Sasaki、Ikuhide Fujisawa、Seiji Iwasa

  DOI：10.1002/chem.201502042

  日期：2015.9.28

  The enantioselective formation of α‐aryloxy‐β‐keto esters is described for the first time. Lewis acid catalyzed enantioselective chlorination of β‐keto esters and subsequent SN2 reactions with phenols yielded α‐aryloxy‐β‐keto esters with up to 96 % ee. Favorskii rearrangement of α‐chloro‐β‐keto esters was also found to give 1,2‐diesters with slightly reduced enantiopurity.

  首次描述了α-芳氧基-β-酮酸酯的对映选择性形成。路易斯酸催化β-酮酯的对映选择性氯化，随后与酚进行S N 2反应，生成ee高达96％的α-芳氧基-β-酮酯 。还发现α-氯-β-酮基酯的Favorskii重排产生1,2-二酯，其对映体纯度略有降低。
• Structural Insight into Peroxisome Proliferator-Activated Receptor γ Binding of Two Ureidofibrate-Like Enantiomers by Molecular Dynamics, Cofactor Interaction Analysis, and Site-Directed Mutagenesis
  作者：Giorgio Pochetti、Nico Mitro、Antonio Lavecchia、Federica Gilardi、Neva Besker、Elena Scotti、Massimiliano Aschi、Nazzareno Re、Giuseppe Fracchiolla、Antonio Laghezza、Paolo Tortorella、Roberta Montanari、Ettore Novellino、Fernando Mazza、Maurizio Crestani、Fulvio Loiodice

  DOI：10.1021/jm9013899

  日期：2010.6.10

  Molecular dynamics simulations were performed on two ureidofibrate-like enantiomers to gain insight into their different potency and efficacy against PPAR gamma. The partial agonism of the Senantiomer seems to be due to its capability to stabilize different regions of the receptor allowing the interaction with both coactivators and corepressors as shown by fluorescence resonance energy transfer (FRET) assays. The recruitment of the corepressor N-CoR1 by the S enantiomer on two different responsive elements of PPAR gamma regulated promoters was confirmed by chromatin immunoprecipitation assays. Cell-based transcription assays show that PPAR gamma coactivator 1 alpha (PGC-1 alpha) and cAMP response element binding protein-binding protein (CBP) enhance the basal and ligand-stimulated receptor activity acting as coactivators of PPAR gamma, whereas the receptor interacting protein 140 (RIP140) and the nuclear corepressor 1 (N-CoR1) repress the transcriptional activity of PPAR gamma. We also tested the importance of the residue Q286 on the transcriptional activity of the receptor by site-directed mutagenesis and confirmed its key role in the stabilization of helix 12. Molecular modeling studies were performed to provide a molecular explanation for the different behavior of the mutants.