Methyl (5E,7Z,10Z,13Z,16Z,19Z)-4-oxo-5,7,10,13,16,19-docosahexaenoate | 845673-73-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: Methyl (5E,7Z,10Z,13Z,16Z,19Z)-4-oxo-5,7,10,13,16,19-docosahexaenoate
• 英文别名: methyl (5E,7Z,10Z,13Z,16Z,19Z)-4-oxodocosa-5,7,10,13,16,19-hexaenoate；4-oxo-docosa-5,7,10,13,16,19-hexaenoic acid methyl ester
• CAS: 845673-73-6
• 化学式: C₂₃H₃₂O₃
• 分子量: 356.505
• InChiKey: LFPDUKVPMXDRGO-MVWYYRFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  26
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Methyl (5E,7Z,10Z,13Z,16Z,19Z)-4-oxo-5,7,10,13,16,19-docosahexaenoate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以65%的产率得到methyl (6E,8E,10Z,13Z,16Z,19Z)-4-oxodocosa-6,8,10,13,16,19-hexaenoate
  参考文献：
  名称：

  Synthesis of docosahexaenoic acid derivatives designed as novel PPARγ agonists and antidiabetic agents

  摘要：

  To discover novel peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists that Could be used as antidiabetic agents, we designed docosahexacnoic acid (DHA) derivatives (2 and 3), which have a hydrophilic substituent at the C(4)-position, based on the crystal structure of the ligand-binding pocket of PPAR gamma. These compounds were synthesized via iodolactolic as a key intermediate. We found that both DHA derivatives (2 and 3) showed PPAR gamma transactivation higher than, or comparable to, that of pioglitazone, which is a TZD derivative used as an antidiabetic agent. DHA derivatives related to these potent Compounds 2 and 3 were also synthesized to study structure-activity relationships. Furthermore, 4-OH DHA 2, which shows strong PPAR gamma transcriptional activity, was separated as an optically pure form. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.074
• 作为产物：
  描述：

  二十二碳六烯酸 在 2,6-二甲基吡啶 、 碘 、 戴斯-马丁氧化剂 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 41.0h， 生成 Methyl (5E,7Z,10Z,13Z,16Z,19Z)-4-oxo-5,7,10,13,16,19-docosahexaenoate
  参考文献：
  名称：

  新型氧杂二十烷酸受体1激动剂的合成，分子模型研究和生物学评价

  摘要：

  氧杂二十烷酸受体1（OXER1）是G蛋白偶联受体（GPCR）家族的成员，并参与炎症过程和致癌作用。因此，它是药理学干预的有吸引力的靶标。本研究旨在使用与天然激动剂5-oxo-ETE相关的化学探针阐明OXER1调控的分子基础。第一步，通过进行简洁，高产的合成，获得了5-oxo-ETE及其密切相关的衍生物（5-oxo-EPE和4-oxo-DHA）。根据效力（EC 50）和功效（E max）进行逮捕。最后，通过分子建模和模拟研究了5-氧代-ETE及其衍生物的结合特性，以合理化生物活性。我们的数据表明，经过测试的5-oxo-ETE衍生物（i）快速插入膜中；（ii）通过跨膜螺旋（TMs）5和6从膜侧进入受体，并且（iii）通过差异来驱动药效和功效与TM5和7相互作用。最重要的是，我们发现5-氧-ETE（1a）的甲酯显示出比天然激动剂（1）更高的最大响应。相反，将5-oxo基团移至4位会导致非活性化合物（4-oxo

  DOI：

  10.1016/j.bmc.2018.05.036

文献信息

• Identification of putative metabolites of docosahexaenoic acid as potent PPARγ agonists and antidiabetic agents
  作者：Keiko Yamamoto、Toshimasa Itoh、Daijiro Abe、Masato Shimizu、Tomoatsu Kanda、Takatoshi Koyama、Masazumi Nishikawa、Tadakazu Tamai、Hiroshi Ooizumi、Sachiko Yamada

  DOI：10.1016/j.bmcl.2004.11.053

  日期：2005.2

  We found that putative metabolites of docosahexaenoic acid (DHA) are strong PPARgamma activators and potential antidiabetic agents. We designed DHA derivatives based on the crystal structure of PPARgamma, synthesized them and evaluated their activities in vitro and in vivo. The efficacy of 5E-4-hydroxy-DHA 2a as a PPARgamma activator was about fourfold stronger than that of pioglitazone. Further-more, the 4-keto derivative (10b) showed antidiabetic activity in animal models without producing undesirable effects such as obesity and hepatotoxicity. (C) 2004 Elsevier Ltd. All rights reserved.
• SYNTHESIS OF RESOLVINS AND INTERMEDIATES, COMPOUNDS PREPARED THEREBY, AND USES THEREOF
  申请人：Rodriguez Ana

  公开号：US20100159540A1

  公开（公告）日：2010-06-24

  Methods are disclosed for the preparation of a new class of lipid mediators known as resolvins, with Resolvin D6 (4,17-dihydroxy-5E,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid) being exemplary. Also disclosed are methods for the efficient synthesis of key intermediates in the preparation of such resolvins, such as isotopically labeled ω-3 fatty acid metabolites, and derivatives and analogs thereof. The invention likewise extends to the intermediates so prepared, and to the resolvins prepared with their use.
• [EN] SYNTHESIS OF RESOLVINS AND INTERMEDIATES, COMPOUNDS PREPARED THEREBY, AND USES THEREOF<br/>[FR] SYNTHÈSE DE RÉSOLVINES ET D'INTERMÉDIAIRES, COMPOSÉS PRÉPARÉS PAR CETTE SYNTHÈSE ET LEURS UTILISATIONS
  申请人：UNIV NEW JERSEY MED

  公开号：WO2008118457A2

  公开（公告）日：2008-10-02

  [EN] Methods are disclosed for the preparation of a new class of lipid mediators known as resolvins, with Resolvin D6 (4,17-dihydroxy-5E,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid) being exemplary. Also disclosed are methods for the efficient synthesis of key intermediates in the preparation of such resolvins, such as isotopically labeled ?-3 fatty acid metabolites, and derivatives and analogs thereof. The invention likewise extends to the intermediates so prepared, and to the resolvins prepared with their use.
  [FR] L'invention concerne des procédés de préparation d'une nouvelle classe de médiateurs lipides nommés résolvines, la résolvine D6 (acide 4,17-dihydroxy-5E,7Z,10Z,13Z,15E,19Z-docosahexaénoïque) en étant un exemple. L'invention concerne également des procédés efficaces de synthèse d'intermédiaires clés pour la préparation de telles résolvines, par exemple les métabolites d'acide gras ?-3 isotopiquement marqués et leurs dérivés et analogues. L'invention concerne également les intermédiaires ainsi préparés et les résolvines préparées en les utilisant.
• Synthesis, molecular modelling studies and biological evaluation of new oxoeicosanoid receptor 1 agonists
  作者：Tomasz Maciej Stepniewski、Mariona Torrens-Fontanals、Ismael Rodríguez-Espigares、Toni Giorgino、Karoline G. Primdahl、Anders Vik、Yngve Stenstrøm、Jana Selent、Trond Vidar Hansen

  DOI：10.1016/j.bmc.2018.05.036

  日期：2018.7

  conducting concise and high-yielding syntheses. The biological activity of obtained compounds was assessed in terms of potency (EC50) and efficacy (Emax) for arrestin recruitment. Finally, molecular modelling and simulation were used to explore binding characteristics of 5-oxo-ETE and derivatives with the aim to rationalize biological activity. Our data suggest that the tested 5-oxo-ETE derivatives (i) insert

  氧杂二十烷酸受体1（OXER1）是G蛋白偶联受体（GPCR）家族的成员，并参与炎症过程和致癌作用。因此，它是药理学干预的有吸引力的靶标。本研究旨在使用与天然激动剂5-oxo-ETE相关的化学探针阐明OXER1调控的分子基础。第一步，通过进行简洁，高产的合成，获得了5-oxo-ETE及其密切相关的衍生物（5-oxo-EPE和4-oxo-DHA）。根据效力（EC 50）和功效（E max）进行逮捕。最后，通过分子建模和模拟研究了5-氧代-ETE及其衍生物的结合特性，以合理化生物活性。我们的数据表明，经过测试的5-oxo-ETE衍生物（i）快速插入膜中；（ii）通过跨膜螺旋（TMs）5和6从膜侧进入受体，并且（iii）通过差异来驱动药效和功效与TM5和7相互作用。最重要的是，我们发现5-氧-ETE（1a）的甲酯显示出比天然激动剂（1）更高的最大响应。相反，将5-oxo基团移至4位会导致非活性化合物（4-oxo
• Synthesis of docosahexaenoic acid derivatives designed as novel PPARγ agonists and antidiabetic agents
  作者：Toshimasa Itoh、Itsuki Murota、Kazuyoshi Yoshikai、Sachiko Yamada、Keiko Yamamoto

  DOI：10.1016/j.bmc.2005.07.074

  日期：2006.1

  To discover novel peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists that Could be used as antidiabetic agents, we designed docosahexacnoic acid (DHA) derivatives (2 and 3), which have a hydrophilic substituent at the C(4)-position, based on the crystal structure of the ligand-binding pocket of PPAR gamma. These compounds were synthesized via iodolactolic as a key intermediate. We found that both DHA derivatives (2 and 3) showed PPAR gamma transactivation higher than, or comparable to, that of pioglitazone, which is a TZD derivative used as an antidiabetic agent. DHA derivatives related to these potent Compounds 2 and 3 were also synthesized to study structure-activity relationships. Furthermore, 4-OH DHA 2, which shows strong PPAR gamma transcriptional activity, was separated as an optically pure form. (c) 2005 Elsevier Ltd. All rights reserved.