ethyl 2-(4-chlorophenoxy)-3-hydroxypentanoate | 848890-32-4

• 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: ethyl 2-(4-chlorophenoxy)-3-hydroxypentanoate
• CAS: 848890-32-4
• 化学式: C₁₃H₁₇ClO₄
• 分子量: 272.729
• InChiKey: POFRPHHGYGSRLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-(4-chlorophenoxy)-3-hydroxypentanoate 在 氢氧化钾 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.5h， 以78%的产率得到2-(4-Chlorophenoxy)-3-hydroxypentanoic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of new clofibrate analogues as potential PPARα agonists

  摘要：

  Clofibrate is a lipid-profile modifying agent belonging to the fibrate class of drugs. Fibrates are known to exhibit their beneficial effects by activating peroxisome proliferator-activated receptor-alpha (PPARalpha) and used in the treatment of dyslipidemia and atherosclerosis and for the prevention of heart failure. Hereby, the preparation of two new sets of clofibrate analogues, ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates and ethyl 2-(4-chlorophenoxy)-3-hydroxyalkanoates is described starting from commercially available 3-oxoalkanoates in fair to good yields. Treatment of 3-oxoalkanoates with SO2Cl2 yielded the corresponding 2-chloro-3-oxoalkanoates, that were then converted into 2-(4-chlorophenoxy)-3-oxoalkanoates by reacting with sodium or caesium 4-chlorophenate. Reduction of the keto group with NaBH4 afforded the corresponding 2-(4-chlorophenoxy)-3-hydroxyalkanoates in very high yields and with variable diastereoselectivity. Biological evaluation of the compounds was performed by a transactivation assay in a transiently transfected monkey kidney fibroblast cell line. The newly synthesised clofibrate analogues failed to show noticeable levels of PPAR activation at concentrations where clofibrate showed an evident activity, suggesting that the structural modifications caused the loss of PPAR activity. (C) 2004 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2004.09.018
• 作为产物：
  描述：

  丙酰乙酸乙酯 在 sodium tetrahydroborate 、 磺酰氯 作用下， 以 甲醇 为溶剂， 反应 4.67h， 生成 ethyl 2-(4-chlorophenoxy)-3-hydroxypentanoate
  参考文献：
  名称：

  Synthesis and biological evaluation of new clofibrate analogues as potential PPARα agonists

  摘要：

  Clofibrate is a lipid-profile modifying agent belonging to the fibrate class of drugs. Fibrates are known to exhibit their beneficial effects by activating peroxisome proliferator-activated receptor-alpha (PPARalpha) and used in the treatment of dyslipidemia and atherosclerosis and for the prevention of heart failure. Hereby, the preparation of two new sets of clofibrate analogues, ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates and ethyl 2-(4-chlorophenoxy)-3-hydroxyalkanoates is described starting from commercially available 3-oxoalkanoates in fair to good yields. Treatment of 3-oxoalkanoates with SO2Cl2 yielded the corresponding 2-chloro-3-oxoalkanoates, that were then converted into 2-(4-chlorophenoxy)-3-oxoalkanoates by reacting with sodium or caesium 4-chlorophenate. Reduction of the keto group with NaBH4 afforded the corresponding 2-(4-chlorophenoxy)-3-hydroxyalkanoates in very high yields and with variable diastereoselectivity. Biological evaluation of the compounds was performed by a transactivation assay in a transiently transfected monkey kidney fibroblast cell line. The newly synthesised clofibrate analogues failed to show noticeable levels of PPAR activation at concentrations where clofibrate showed an evident activity, suggesting that the structural modifications caused the loss of PPAR activity. (C) 2004 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2004.09.018

文献信息

• Screening yeasts for the stereoselective reduction of oxoester clofibrate analogues
  作者：Maria Grazia Perrone、Ernesto Santandrea、Antonio Scilimati、Christoph Syldatk、Vincenzo Tortorella

  DOI：10.1016/j.tetasy.2005.02.010

  日期：2005.4

  Reduction of oxoesters 1b-d and 1fg in the presence of different yeast strains (Saccharomyces cerevisiae DSM 11285, S. cerevisiae CBS 7336, Cryptococcus curvatus ATCC 20509, Candida hombicola ATCC 22214, Trigonopsis variabilis DSM 70714, Kluyveromyces marxianus CBS 6556) affords hydroxy esters 2b-d and 2fg with diastereoisomeric excesses (de) up to > 99%. Hydrolytic enzyme(s) contained in the yeasts catalyzed to some extent the hydrolysis of the oxoesters to the corresponding acids, which undergo decarboxylation followed by reduction of the carbonyl moiety. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of new clofibrate analogues as potential PPARα agonists
  作者：Maria Grazia Perrone、Ernesto Santandrea、Natalina Dell’Uomo、Fabio Giannessi、Ferdinando Maria Milazzo、Anna Floriana Sciarroni、Antonio Scilimati、Vincenzo Tortorella

  DOI：10.1016/j.ejmech.2004.09.018

  日期：2005.2

  Clofibrate is a lipid-profile modifying agent belonging to the fibrate class of drugs. Fibrates are known to exhibit their beneficial effects by activating peroxisome proliferator-activated receptor-alpha (PPARalpha) and used in the treatment of dyslipidemia and atherosclerosis and for the prevention of heart failure. Hereby, the preparation of two new sets of clofibrate analogues, ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates and ethyl 2-(4-chlorophenoxy)-3-hydroxyalkanoates is described starting from commercially available 3-oxoalkanoates in fair to good yields. Treatment of 3-oxoalkanoates with SO2Cl2 yielded the corresponding 2-chloro-3-oxoalkanoates, that were then converted into 2-(4-chlorophenoxy)-3-oxoalkanoates by reacting with sodium or caesium 4-chlorophenate. Reduction of the keto group with NaBH4 afforded the corresponding 2-(4-chlorophenoxy)-3-hydroxyalkanoates in very high yields and with variable diastereoselectivity. Biological evaluation of the compounds was performed by a transactivation assay in a transiently transfected monkey kidney fibroblast cell line. The newly synthesised clofibrate analogues failed to show noticeable levels of PPAR activation at concentrations where clofibrate showed an evident activity, suggesting that the structural modifications caused the loss of PPAR activity. (C) 2004 Elsevier SAS. All rights reserved.