ethyl (3S,4E)-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pent-4-enoate | 1007220-96-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (3S,4E)-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pent-4-enoate
• 英文别名: Ethyl (3S,4E)-3-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pent-4-enoate；ethyl (E,3S)-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pent-4-enoate
• CAS: 1007220-96-3
• 化学式: C₁₄H₂₅BO₄
• 分子量: 268.161
• InChiKey: ZPRMXENZYRKDPF-ANYFNZRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.76
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (3S,4E)-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pent-4-enoate 、 2-[(1E,3E)-4-iodo-3-methylbuta-1,3-dien-1-yl]-1,3,3-trimethylcyclohex-1-ene 在 四(三苯基膦)钯 氢氧化铊(Ⅰ) 作用下， 以 四氢呋喃 为溶剂， 反应 2.08h， 以54%的产率得到ethyl (13S)-13,14-dihydroretinoate
  参考文献：
  名称：

  Stereospecificity of Retinol Saturase:  Absolute Configuration, Synthesis, and Biological Evaluation of Dihydroretinoids

  摘要：

  Retinol saturase carries out a stereospecific saturation of the C13-C14 double bond of all-trans-retinol to generate (13R)-all-trans-13,14-dihydroretinol. This compound is found in cells expressing mouse or zebrafish retinol saturase and in the livers of mice fed retinyl palmitate. All-trans-13,14-dihydroretinol is oxidized in vivo to all-trans-13,14-dihydroretinoic acid, a highly selective agonist of the retinoic acid receptor. The naturally occurring (13R)-all-trans-13,14-dihydroretinoic acid is a weaker agonist than the (13S) enantiomer, indicating enantioselective recognition by the ligand-binding pocket of this receptor. Consequently the (13S) enantiomer, acting through the retinoic acid receptor, also inhibits adipose differentiation more potently than the (13R) enantiomer.

  DOI：

  10.1021/ja710487q
• 作为产物：
  描述：

  (S)-ethyl 3-methyl-4-oxobutanoate 、 频哪醇(二氯甲基)硼酸酯 在 chromium dichloride 、 lithium iodide 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 以65%的产率得到ethyl (3S,4E)-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pent-4-enoate
  参考文献：
  名称：

  Stereospecificity of Retinol Saturase:  Absolute Configuration, Synthesis, and Biological Evaluation of Dihydroretinoids

  摘要：

  Retinol saturase carries out a stereospecific saturation of the C13-C14 double bond of all-trans-retinol to generate (13R)-all-trans-13,14-dihydroretinol. This compound is found in cells expressing mouse or zebrafish retinol saturase and in the livers of mice fed retinyl palmitate. All-trans-13,14-dihydroretinol is oxidized in vivo to all-trans-13,14-dihydroretinoic acid, a highly selective agonist of the retinoic acid receptor. The naturally occurring (13R)-all-trans-13,14-dihydroretinoic acid is a weaker agonist than the (13S) enantiomer, indicating enantioselective recognition by the ligand-binding pocket of this receptor. Consequently the (13S) enantiomer, acting through the retinoic acid receptor, also inhibits adipose differentiation more potently than the (13R) enantiomer.

  DOI：

  10.1021/ja710487q

文献信息

• Methods for treating obesity or an obesity related condition
  申请人：Case Western Reserve University

  公开号：US08889660B2

  公开（公告）日：2014-11-18

  In one aspect of the present invention, a pharmaceutical composition for treating a metabolic disease in a mammalian subject includes a therapeutically effective amount of (R)-all-trans-13,14-dihydroretinol and a pharmaceutically acceptable carrier or diluent. In another aspect of the present invention, pharmaceutical composition for treating a metabolic disease in a mammalian subject includes a therapeutically effective amount of (S)-all-trans-13,14-dihydroretinol and a pharmaceutically acceptable carrier or diluent. In a further aspect of the present invention, a method is provided for treating a metabolic disease in a mammalian subject. The method includes administering to the subject a pharmaceutical composition comprising at least one all-trans-13,14-dihydroretinoid, all-trans-13,14-dihydroretinoid derivative, or agent capable of modulating the level of at least one all-trans-13,14-dihydroretinoid or all-trans-13,14-dihydroretinoid derivative in the subject.

  在本发明的一个方面中，用于治疗哺乳动物主体代谢性疾病的制药组合物包括治疗有效量的（R）-全反式-13,14-二氢视黄醇和药学上可接受的载体或稀释剂。在本发明的另一个方面中，用于治疗哺乳动物主体代谢性疾病的制药组合物包括治疗有效量的（S）-全反式-13,14-二氢视黄醇和药学上可接受的载体或稀释剂。在本发明的进一步方面中，提供了一种用于治疗哺乳动物主体代谢性疾病的方法。该方法包括向主体注射至少一种全反式-13,14-二氢视黄醇、全反式-13,14-二氢视黄醇衍生物或能够调节主体中至少一种全反式-13,14-二氢视黄醇或全反式-13,14-二氢视黄醇衍生物水平的药物组合物。
• COMPOSITIONS AND METHODS FOR TREATING METABOLIC DISEASES
  申请人：CASE WESTERN RESERVE UNIVERSITY

  公开号：US20130072555A1

  公开（公告）日：2013-03-21

  In one aspect of the present invention, a pharmaceutical composition for treating a metabolic disease in a mammalian subject includes a therapeutically effective amount of (R)-all-trans-13,14-dihydroretinol and a pharmaceutically acceptable carrier or diluent. In another aspect of the present invention, pharmaceutical composition for treating a metabolic disease in a mammalian subject includes a therapeutically effective amount of (S)-all-trans-13,14-dihydroretinol and a pharmaceutically acceptable carrier or diluent. In a further aspect of the present invention, a method is provided for treating a metabolic disease in a mammalian subject. The method includes administering to the subject a pharmaceutical composition comprising at least one all-trans-13,14-dihydroretinoid, all-trans-13,14-dihydroretinoid derivative, or agent capable of modulating the level of at least one all-trans-13,14-dihydroretinoid or all-trans-13,14-dihydroretinoid derivative in the subject.

  在本发明的一个方面中，用于治疗哺乳动物主体的代谢疾病的药物组合物包括(R)-全反式-13,14-二氢视黄醇的治疗有效量和药学上可接受的载体或稀释剂。在本发明的另一方面中，用于治疗哺乳动物主体的代谢疾病的药物组合物包括(S)-全反式-13,14-二氢视黄醇的治疗有效量和药学上可接受的载体或稀释剂。在本发明的进一步方面中，提供了一种用于治疗哺乳动物主体的代谢疾病的方法。该方法包括向主体注射至少一种全反式-13,14-二氢视黄醇、全反式-13,14-二氢视黄醇衍生物或能够调节主体内至少一种全反式-13,14-二氢视黄醇或全反式-13,14-二氢视黄醇衍生物水平的药物组合物。
• Stereospecificity of Retinol Saturase:  Absolute Configuration, Synthesis, and Biological Evaluation of Dihydroretinoids
  作者：Alexander R. Moise、Marta Domínguez、Susana Alvarez、Rosana Alvarez、Michael Schupp、Ana G. Cristancho、Philip D. Kiser、Angel R. de Lera、Mitchell A. Lazar、Krzysztof Palczewski

  DOI：10.1021/ja710487q

  日期：2008.1.30

  Retinol saturase carries out a stereospecific saturation of the C13-C14 double bond of all-trans-retinol to generate (13R)-all-trans-13,14-dihydroretinol. This compound is found in cells expressing mouse or zebrafish retinol saturase and in the livers of mice fed retinyl palmitate. All-trans-13,14-dihydroretinol is oxidized in vivo to all-trans-13,14-dihydroretinoic acid, a highly selective agonist of the retinoic acid receptor. The naturally occurring (13R)-all-trans-13,14-dihydroretinoic acid is a weaker agonist than the (13S) enantiomer, indicating enantioselective recognition by the ligand-binding pocket of this receptor. Consequently the (13S) enantiomer, acting through the retinoic acid receptor, also inhibits adipose differentiation more potently than the (13R) enantiomer.