ethyl (2S,3R)-2-(4-chlorophenoxy)-3-hydroxybutanoate | 849704-24-1

• 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: ethyl (2S,3R)-2-(4-chlorophenoxy)-3-hydroxybutanoate
• CAS: 849704-24-1
• 化学式: C₁₂H₁₅ClO₄
• 分子量: 258.702
• InChiKey: YKDDRVBXECKGDI-KCJUWKMLSA-N

物化性质

• 沸点：
  382.5±27.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 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 (2S,3R)-2-(4-chlorophenoxy)-3-hydroxybutanoate 在 氢氧化钾 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以100%的产率得到(2S,3R)-2-(4-chlorophenoxy)-3-hydroxybutanoic acid
  参考文献：
  名称：

  Reaction of caesium 4-chlorophenate and chlorohydrins from threonines: synthesis of clofibrate analogues

  摘要：

  Clofibrate is a well-known peroxisome prolifierator-activated receptor-alpha (PPARalpha) agonist, used in the treatment of hyperlipaemias and atherosclerosis and to prevent heart failure. Herein, the preparation of the four enantiomerically pure stereoisomers of ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate as clofibrate analogues is described. Biological evaluation of these new compounds was performed by a transactivation assay in a transiently transfected monkey kidney fibroblast cell line. All four diastereomers were inactive even at 300 muM, where clofibrate showed an evident activity, suggesting that the designed clofibrate molecular structural modifications in the analogues caused the loss of peroxisome proliferator-activated receptor-alpha (PPARalpha) activity. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2005.01.006
• 作为产物：
  描述：

  caesium 4-chlorophenate 在 Trigonopsis variabilis DSM 70714 作用下， 以 乙醇 为溶剂， 反应 33.0h， 生成 ethyl (2S,3R)-2-(4-chlorophenoxy)-3-hydroxybutanoate
  参考文献：
  名称：

  Diastereo- and enantioselective bioreduction of ethyl 2-(4-chlorophenoxy)-3-oxobutanoate clofibrate analogues by Kluyveromyces marxianus and other whole cell biocatalysts

  摘要：

  Growing and resting cells of several yeasts, which catalyze the hydride transfer to a carbonyl, were screened and used in conditions to find out the suitable methodology to prepare clofibrate analogues. Clofibrate is an antilipidemic drug. In particular, the bioreduction of ethyl 2-(4-chlorophenoxy)-3-oxobutanoate 1 was investigated to separately prepare the four possible stereoisomers of the ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate 2. Compound (2R,3S)-2 was prepared with ee = 97% and 73% yield in the presence of Kluyveromyces marxianus; (2S,3S)-2 preparation with ee > 99% in 9% and 33% yield was mediated by Saccharomyces cerevisiae CBS 7336 and Trigonopsis variabilis, respectively. Diastereomeric excess values of all the reactions investigated were up to > 99%. Furthermore, enantiomeric excesses of the bioconversions varied between 2% and > 99% using growing cells and, 12% and > 99% using resting cells. The absolute configuration of (2R,3S)-2 was established by X-ray analysis of the corresponding acid 3. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.08.028

文献信息

• Baker’s yeast-mediated reduction of ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates intermediates for potential PPARα ligands
  作者：Maria Grazia Perrone、Ernesto Santandrea、Antonio Scilimati、Vincenzo Tortorella、Francesco Capitelli、Valerio Bertolasi

  DOI：10.1016/j.tetasy.2004.08.027

  日期：2004.11

  Several 2-(4-chlorophenoxy)-3-oxoesters were prepared in fair to good yields and then reduced in the presence of baker's yeast to the corresponding alcohols having de's up to 92% and ee's > 99%. The absolute configuration of nearly enantiomerically pure ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate was assigned by both comparison of the sign of the specific rotation and HPLC retention times of authentic samples prepared from threonines. Reduction of ethyl 2-(4-chlorophenoxy)-3-oxo-4-phenylbutanoate afforded only enantiomerically pure ethyl (2R,3S)-2-(4-chlorophenoxy)-3-hydroxy-4-phenylbutanoate (out of the four possible stereoisomers), whose absolute configuration was established by single crystal X-ray analysis. Furthermore, reduction of ethyl 2-methyl-2-(4-chlorophenoxy)-3-hydroxybutanoate with a quaternary stereogenic carbon (C-2) gave both of the two expected diastereoisomers with ee = 95% and 96%. Insight into the mechanism of baker's yeast-mediated reduction of prochiral ketoesters is also reported. (C) 2004 Elsevier Ltd. All rights reserved.
• Reaction of caesium 4-chlorophenate and chlorohydrins from threonines: synthesis of clofibrate analogues
  作者：Maria Grazia Perrone、Ernesto Santandrea、Leonardo Di Nunno、Antonio Scilimati、Vincenzo Tortorella、Francesco Capitelli、Valerio Bertolasi

  DOI：10.1016/j.tetasy.2005.01.006

  日期：2005.2

  Clofibrate is a well-known peroxisome prolifierator-activated receptor-alpha (PPARalpha) agonist, used in the treatment of hyperlipaemias and atherosclerosis and to prevent heart failure. Herein, the preparation of the four enantiomerically pure stereoisomers of ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate as clofibrate analogues is described. Biological evaluation of these new compounds was performed by a transactivation assay in a transiently transfected monkey kidney fibroblast cell line. All four diastereomers were inactive even at 300 muM, where clofibrate showed an evident activity, suggesting that the designed clofibrate molecular structural modifications in the analogues caused the loss of peroxisome proliferator-activated receptor-alpha (PPARalpha) activity. (C) 2005 Elsevier Ltd. All rights reserved.
• Diastereo- and enantioselective bioreduction of ethyl 2-(4-chlorophenoxy)-3-oxobutanoate clofibrate analogues by Kluyveromyces marxianus and other whole cell biocatalysts
  作者：Maria Grazia Perrone、Ernesto Santandrea、Antonio Scilimati、Christoph Syldatk、Vincenzo Tortorella、Francesco Capitelli、Valerio Bertolasi

  DOI：10.1016/j.tetasy.2004.08.028

  日期：2004.11

  Growing and resting cells of several yeasts, which catalyze the hydride transfer to a carbonyl, were screened and used in conditions to find out the suitable methodology to prepare clofibrate analogues. Clofibrate is an antilipidemic drug. In particular, the bioreduction of ethyl 2-(4-chlorophenoxy)-3-oxobutanoate 1 was investigated to separately prepare the four possible stereoisomers of the ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate 2. Compound (2R,3S)-2 was prepared with ee = 97% and 73% yield in the presence of Kluyveromyces marxianus; (2S,3S)-2 preparation with ee > 99% in 9% and 33% yield was mediated by Saccharomyces cerevisiae CBS 7336 and Trigonopsis variabilis, respectively. Diastereomeric excess values of all the reactions investigated were up to > 99%. Furthermore, enantiomeric excesses of the bioconversions varied between 2% and > 99% using growing cells and, 12% and > 99% using resting cells. The absolute configuration of (2R,3S)-2 was established by X-ray analysis of the corresponding acid 3. (C) 2004 Elsevier Ltd. All rights reserved.