4-hydroxy,5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid γ-lactone | 825632-99-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 4-hydroxy,5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid γ-lactone
• 英文别名: 5-[(1E,3Z,6Z,9Z,12Z,15Z)-octadeca-1,3,6,9,12,15-hexaenyl]dihydro-2(3H)-furanone；5-((1E,3Z,6Z,9Z,12Z,15Z)-Octadeca-1,3,6,9,12,15-hexaen-1-yl)dihydrofuran-2(3H)-one；5-[(1E,3Z,6Z,9Z,12Z,15Z)-1,3,6,9,12,15-octadecahexaenyl]dihydro-2(3H)-furanone；5-[(1E,3Z,6Z,9Z,12Z,15Z)-octadeca-1,3,6,9,12,15-hexaenyl]oxolan-2-one
• CAS: 825632-99-3
• 化学式: C₂₂H₃₀O₂
• 分子量: 326.479
• InChiKey: WCLSJZFZJIIXNP-PQVBWYSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-hydroxy,5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid γ-lactone 在 二异丁基氢化铝 作用下， 生成 (5E,7Z,10Z,13Z,16Z,19Z)-docosa-5,7,10,13,16,16-hexaene-1,4-diol
  参考文献：
  名称：

  Identification of putative metabolites of docosahexaenoic acid as potent PPARγ agonists and antidiabetic agents

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2004.11.053
• 作为产物：
  描述：

  二十二碳六烯酸 在 2,6-二甲基吡啶 、 碘 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 31.0h， 生成 4-hydroxy,5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid γ-lactone
  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

• Synthesis of polyconjugated fatty acids
  申请人：Smith William

  公开号：US20050014826A1

  公开（公告）日：2005-01-20

  The present invention relates to fatty acids. In particular, the present invention provides polyconjugated fatty acids, and methods of their synthesis and their use.

  本发明涉及脂肪酸。具体来说，本发明提供了多共轭脂肪酸，以及它们的合成方法和用途。
• Synthesis of long chain n-3 and n-6 fatty acids having a photoactive conjugated tetraene group
  作者：Dmitry V. Kuklev、William L. Smith

  DOI：10.1016/j.chemphyslip.2004.02.006

  日期：2004.7

  Fatty acids of the n-3 and n-6 families containing a photoactive conjugated tetraene group near the carboxylate were prepared from several naturally occurring fatty acids by sequential iodolactonization and treatment with excess 1,8-diazabicyclo[5.4.0]undec-7-ene. The new conjugated fatty acids include 5E,7E,9E,11Z,14Z- and 5E,7E,9E,11E,14Z-eicosapentaenoic acids derived from arachidonic acid; 5E,7E

  通过顺序的碘代内酯化并用过量的1,8-二氮杂双环[5.4.0] undec-7-处理，由几种天然存在的脂肪酸制备n-3和n-6家族，其中的羧酸在羧酸酯附近包含一个光敏共轭四烯基团的脂肪酸。烯。新的共轭脂肪酸包括衍生自花生四烯酸的5E，7E，9E，11Z，14Z-和5E，7E，9E，11E，14Z-二十碳五烯酸。来自二十碳五烯酸的5E，7E，9E，11Z，14Z，17Z-和5E，7E，9E，11E，14Z，17Z-二十碳六烯酸; 和来自二十二碳六烯酸的4E，6E，8E，10Z，13Z，16Z，19Z-和4E，6E，8E，10E，13Z，16Z，19Z-二十二碳六烯酸。所有新合成的脂肪酸均通过UV，1H NMR和质谱进行了表征。这些新产品代表了亚甲基间断双键系统定向共轭的第一个例子。可以以克量和高产率（> 50％）合成产物。有趣的是，即使使用温和的条件和不同的合成方法，也无法合成在羧基附近具有
• THERAPEUTIC AGENT FOR ULCERATIVE COLITIS AND/OR CROHN'S DISEASE
  申请人：Yamamoto, Keiko

  公开号：EP1946754A1

  公开（公告）日：2008-07-23

  Disclosed is an agent for preventing or treating ulcerative colitis, Crohn's disease, and/or Behcet's disease. A therapeutic agent for ulcerative colitis, Crohn's disease, and/or Behcet's disease, comprising a polyunsaturated fatty acid derivative represented by the following formula (1) as an active ingredient.

  本发明公开了一种用于预防或治疗溃疡性结肠炎、克罗恩病和/或白塞氏病的制剂。一种治疗溃疡性结肠炎、克罗恩病和/或白塞氏病的药剂，由下式（1）代表的多不饱和脂肪酸衍生物作为活性成分组成。
• 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.
• EP1946754
  申请人：——

  公开号：——

  公开（公告）日：——