15-氧代-5,8,11-顺式-13-反式-二十碳四烯酸 | 81416-72-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 15-氧代-5,8,11-顺式-13-反式-二十碳四烯酸
• 英文名称: 15-oxo-ETE
• 英文别名: 15-oxoeicosatetraenoic acid；(5Z,8Z,11Z,13E)-15-oxoicosa-5,8,11,13-tetraenoic acid
• CAS: 81416-72-0
• 化学式: C₂₀H₃₀O₃
• 分子量: 318.456
• InChiKey: YGJTUEISKATQSM-USWFWKISSA-N

物化性质

• 沸点：
  495.0±45.0 °C(Predicted)
• 密度：
  0.980±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：可混溶； DMSO：可混溶；乙醇：可混溶； PBS pH 7.2：0.8 mg/mL
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  23
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  -20°C，密闭保存，干燥条件

制备方法与用途

15-氧代ETE是由15-羟基15-HETE经过氧化生成的。

反应信息

• 作为反应物：
  描述：

  15-氧代-5,8,11-顺式-13-反式-二十碳四烯酸 在 phosphate buffer 、 硼氘化钠 作用下， 以 氯仿 为溶剂， 反应 0.08h， 以80%的产率得到(15-2H,5Z,8Z,11Z,13E)-15-hydroxy-5,8,11,13-eicosatetraenoic acid
  参考文献：
  名称：

  用Fenton试剂对15-（S）-羟基二十碳四烯酸进行自由基氧化：从七三烯基自由基途径表征环氧-醇和具有细胞毒性的4-羟基-2E-壬烯醛。

  摘要：

  用Fenton试剂（Fe2 + / EDTA / H2O2）氧化（5Z，8Z，11Z，13E，15S）-15-羟基-5,8,11,13-二十碳四烯酸（15-（S）-HETE，1a） ）进行了调查。在pH 7.4的磷酸盐缓冲液中，反应进行1小时后消耗了75％的底物，得到了一种混合物，其中一种被鉴定为（2E，4S）-4-hydroxy-2-nonenal（3a，收率18％ ）。将混合物与重氮甲烷甲基化，可以分离出另一种主要产物，该产物可以鉴定为（5Z，8Z，13E）-11,12-反式环氧-15-羟基-5,8,13-二十碳三烯酸甲酯（2a甲基酯， 8％的产率）。在（15-（2）H）-15-HETE（1b）上进行的类似氧化反应表明标记完全保留在2b甲酯和3b中，与氧化路径有关，该路径涉及C为H原子的主要事件-10。全面的，

  DOI：

  10.1016/j.chemphyslip.2006.02.015
• 作为产物：
  描述：

  (15S,5Z,8Z,11Z,13E)-15-羟基二十碳四烯酸 在 2-碘酰基苯甲酸 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以95%的产率得到15-氧代-5,8,11-顺式-13-反式-二十碳四烯酸
  参考文献：
  名称：

  用Fenton试剂对15-（S）-羟基二十碳四烯酸进行自由基氧化：从七三烯基自由基途径表征环氧-醇和具有细胞毒性的4-羟基-2E-壬烯醛。

  摘要：

  用Fenton试剂（Fe2 + / EDTA / H2O2）氧化（5Z，8Z，11Z，13E，15S）-15-羟基-5,8,11,13-二十碳四烯酸（15-（S）-HETE，1a） ）进行了调查。在pH 7.4的磷酸盐缓冲液中，反应进行1小时后消耗了75％的底物，得到了一种混合物，其中一种被鉴定为（2E，4S）-4-hydroxy-2-nonenal（3a，收率18％ ）。将混合物与重氮甲烷甲基化，可以分离出另一种主要产物，该产物可以鉴定为（5Z，8Z，13E）-11,12-反式环氧-15-羟基-5,8,13-二十碳三烯酸甲酯（2a甲基酯， 8％的产率）。在（15-（2）H）-15-HETE（1b）上进行的类似氧化反应表明标记完全保留在2b甲酯和3b中，与氧化路径有关，该路径涉及C为H原子的主要事件-10。全面的，

  DOI：

  10.1016/j.chemphyslip.2006.02.015

文献信息

• Formation of a Cyclopropyl Epoxide via a Leukotriene A Synthase-related Pathway in an Anaerobic Reaction of Soybean Lipoxygenase-1 with 15S-Hydroperoxyeicosatetraenoic Acid
  作者：Yuxiang Zheng、Alan R. Brash

  DOI：10.1074/jbc.m109.084632

  日期：2010.4

  The further conversion of an arachidonic acid hydroperoxide to a leukotriene A (LTA) type epoxide by specific lipoxygenase (LOX) enzymes constitutes a key step in inflammatory mediator biosynthesis. Whereas mammalian 5-LOX transforms its primary product (5S-hydroperoxyeicosatetraenoic acid; 5S-HPETE) almost exclusively to LTA(4), the model enzyme, soybean LOX-1, normally produces no detectable leukotrienes

  通过特定的脂氧合酶 (LOX) 将花生四烯酸氢过氧化物进一步转化为白三烯 A (LTA) 型环氧化物是炎症介质生物合成的关键步骤。尽管哺乳动物 5-LOX 将其主要产物（5S-氢过氧二十碳四烯酸；5S-HPETE）几乎完全转化为 LTA(4)，但模型酶大豆 LOX-1 通常不会产生可检测到的白三烯，而是进一步氧化其主要产物 15S- HPETE 为 5,15- 和 8,15-二氢过氧化物。哺乳动物 15-LOX-1 显示这两种类型的活性。我们推断，LOX 活性位点内分子氧的可用性有利于氧合作用，而 O(2) 的缺乏则促进 LTA 环氧化物的合成。为了测试这一点，我们在厌氧条件下使 15S-HPETE 与大豆 LOX-1 反应，并通过高压液相色谱、紫外、质谱和核磁共振鉴定产物。在这些产品中，我们鉴定了一对具有全反式共轭三烯的 8,15-二羟基非对映体，它们在 C-8 处从 H(2)(18)O
• Lipoxin compounds
  申请人：The Brigham & Women's Hospital, Inc.

  公开号：EP1657233A1

  公开（公告）日：2006-05-17

  Compounds having the active site of natural lipoxins, but a longer tissue half-life are disclosed. These small molecules are useful for treating vasoconstrictive, inflammatory, myeloid suppressive, cardiovascular, and gastroinestinal diseases.

  已公开的化合物具有天然脂毒素的活性位点，但组织半衰期更长。这些小分子化合物可用于治疗血管收缩性疾病、炎症性疾病、骨髓抑制性疾病、心血管疾病和胃肠道疾病。
• NOVEL ANTI-INFLAMMATORY COMPOUNDS
  申请人：The University of Tokyo

  公开号：EP2415748A1

  公开（公告）日：2012-02-08

  An object of the present invention is to provide a compound having a novel structure for overcoming the defects of conventional steroid agents and NSAIDs. It is found that the particular dihydroxy bodies of eicosapentaenoic acid and docosahexaenoic acid, which have not conventionally been known (11,18-dihydoxy eicosapentaenoic acid (11,18-diHEPE), 17,18-dihydroxy eicosapentaenoic acid (17,18-diHEPE) etc.), have activity of inhibiting neutrophil, thereby solving the object. The present invention unexpectedly remarkably inhibits infiltration into a tissue of, and activation of neutrophil found out at acute inflammation. The compound of the present invention is a compound which has not conventionally been known. Therefore, utility as a new therapeutic is provided.

  本发明的目的是提供一种具有新型结构的化合物，以克服传统类固醇制剂和非甾体抗炎药的缺陷。本发明发现，传统上未知的二十碳五烯酸和二十二碳六烯酸的特定二羟基体（11,18-二羟基二十碳五烯酸（11,18-diHEPE）、17,18-二羟基二十碳五烯酸（17,18-diHEPE）等）具有抑制中性粒细胞的活性，从而解决了上述目的。本发明意外地显著抑制了急性炎症时发现的中性粒细胞对组织的浸润和活化。本发明的化合物是一种传统上不为人所知的化合物。因此，本发明可作为一种新疗法使用。
• Physcomitrella patens has lipoxygenases for both eicosanoid and octadecanoid pathways
  作者：Aldwin Anterola、Cornelia Göbel、Ellen Hornung、George Sellhorn、Ivo Feussner、Howard Grimes

  DOI：10.1016/j.phytochem.2008.11.012

  日期：2009.1

  Mosses have substantial amounts of long chain C20 polyunsaturated fatty acids, such as arachidonic and eicosapentaenoic acid, in addition to the shorter chain C18 alpha-linolenic and linoleic acids, which are typical substrates of lipoxygenases in flowering plants. To identify the fatty acid substrates used by moss lipoxygenases, eight lipoxygenase genes from Physcomitrella patens were heterologously expressed in Escherichia coli, and then analyzed for lipoxygenase activity using linoleic, alpha-linolenic and arachidonic acids as substrates. Among the eight moss lipoxygenases, only seven were found to be enzymatically active in vitro, two of which selectively used arachidonic acid as the substrate, while the other five preferred alpha-linolenic acid. Based on enzyme assays using a Clark-type oxygen electrode, all of the active lipoxygenases had an optimum pH at 7.0, except for one with highest activity at pH 5.0. HPLC analyses indicated that the two arachidonic acid lipoxygenases form (12S)-hydroperoxy eicosatetraenoic acid as the main product, while the other five lipoxygenases produce mainly (13S)-hydroperoxy octadecatrienoic acid from alpha-linolenic acid. These results suggest that mosses may have both C20 and C18 based oxylipin pathways. Published by Elsevier Ltd.
• Inhibitory and mechanistic investigations of oxo-lipids with human lipoxygenase isozymes
  作者：Michelle M. Armstrong、Giovanni Diaz、Victor Kenyon、Theodore R. Holman

  DOI：10.1016/j.bmc.2014.05.025

  日期：2014.8

  Oxo-lipids, a large family of oxidized human lipoxygenase (hLOX) products, are of increasing interest to researchers due to their involvement in different inflammatory responses in the cell. Oxo-lipids are unique because they contain electrophilic sites that can potentially form covalent bonds through a Michael addition mechanism with nucleophilic residues in protein active sites and thus increase inhibitor potency. Due to the resemblance of oxo-lipids to LOX substrates, the inhibitor potency of 4 different oxo-lipids; 5-oxo-6,8,11,14-(E,Z,Z,Z)-eicosatetraenoic acid (5-oxo-ETE), 15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE), 12-oxo-5,8,10,14-(Z,Z,E,Z)-eicosatetraenoic acid (12-oxo-ETE), and 13-oxo-9,11-(Z,E)-octadecadienoic acid (13-oxo-ODE) were determined against a library of LOX isozymes; leukocyte 5-lipoxygenase (h5-LOX), human reticulocyte 15-lipoxygenase-1 (h15-LOX-1), human platelet 12-lipoxygenase (h12-LOX), human epithelial 15-lipoxygenase-2 (h15-LOX-2), soybean 15-lipoxygenase-1 (s15-LOX-1), and rabbit reticulocyte 15-LOX (r15-LOX). 15-Oxo-ETE exhibited the highest potency against h12-LOX, with an IC50 = 1 +/- 0.1 mu M and was highly selective. Steady state inhibition kinetic experiments determined 15-oxo-ETE to be a mixed inhibitor against h12-LOX, with a K-ic value of 0.087 +/- 0.008 mu M and a K-iu value of 2.10 +/- 0.8 mu M. Time-dependent studies demonstrated irreversible inhibition with 12-oxo-ETE and h15-LOX-1, however, the concentration of 12-oxo-ETE required (K-i = 36.8 +/- 13.2 mu M) and the time frame (k(2) = 0.0019 +/- 0.00032 s(-1)) were not biologically relevant. These data are the first observations that oxo-lipids can inhibit LOX isozymes and may be another mechanism in which LOX products regulate LOX activity. (C) 2014 Elsevier Ltd. All rights reserved.