17,18-Epoxyeicosatetraenoic acid | 1283063-45-5

• 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: 17,18-Epoxyeicosatetraenoic acid
• 英文别名: 17,18-EpETE；17,18-EEQ；17(18)-EpETE；(5Z,8Z,11Z,14Z)-16-(3-ethyloxiran-2-yl)hexadeca-5,8,11,14-tetraenoic acid
• CAS: 1283063-45-5
• 化学式: C₂₀H₃₀O₃
• 分子量: 318.456
• InChiKey: GPQVVJQEBXAKBJ-JPURVOHMSA-N

物化性质

• 沸点：
  464.6±33.0 °C(Predicted)
• 密度：
  0.996±0.06 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  17,18-Epoxyeicosatetraenoic acid 在 porcine 12-lipoxygenase 作用下， 以 aq. buffer 为溶剂， 反应 13.17h， 生成
  参考文献：
  名称：

  Eicosapentaenoic acid is converted via ω‐3 epoxygenation to the anti‐inflammatory metabolite 12‐hydroxy‐17,18‐epoxyeicosatetraenoic acid

  摘要：

  Eicosapentaenoic acid (EPA) has beneficial effects in many inflammatory disorders. In this study, dietary EPA was converted to 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) by -3 epoxygenation in the mouse peritoneal cavity. Mediator lipidomics revealed a series of novel oxygenated metabolites of 17,18-EpETE, and one of the major metabolites, 12-hydroxy-17,18-epoxyeicosatetraenoic acid (12-OH-17,18-EpETE), displayed a potent anti-inflammatory action by limiting neutrophil infiltration in murine zymosan-induced peritonitis. 12-OH-17,18-EpETE inhibited leukotriene B-4-induced neutrophil chemotaxis and polarization in vitro in a low nanomolar range (EC50 0.6 nM). The complete structures of two natural isomers were assigned as 12S-OH-17R,18S-EpETE and 12S-OH-17S,18R-EpETE, using chemically synthesized stereoisomers. These natural isomers displayed potent anti-inflammatory action, whereas the unnatural stereoisomers were essentially devoid of activity. These results demonstrate that 17,18-EpETE derived from dietary EPA is converted to a potent bioactive metabolite 12-OH-17,18-EpETE, which may generate an endogenous anti-inflammatory metabolic pathway.Kubota, T., Arita, M., Isobe, Y., Iwamoto, R., Goto, T., Yoshioka, T., Urabe, D., Inoue, M., Arai, H. Eicosapentaenoic acid is converted via -3 epoxygenation to the anti-inflammatory metabolite 12-hydroxy-17,18-epoxyeicosatetraenoic acid.

  DOI：

  10.1096/fj.13-236224
• 作为产物：
  描述：

  全顺式二十碳五烯酸 在 human recombinant cytochrome P₄₅₀ 1A₁ 作用下， 以100%的产率得到17,18-Epoxyeicosatetraenoic acid
  参考文献：
  名称：

  Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450

  摘要：

  Cytochromes P450 (CYPs) metabolize polyunsaturated long-chain fatty acids (PUFA-LC) to several classes of oxygenated metabolites. Through use of human recombinant CYPs, we recently showed that CYP1A1, -2C19, -2D6, -2E1, and -3A4 are mainly hydroxylases, whereas CYP1A2, -2C8, -2C9, and -2J2 are mainly epoxygenases of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), respectively. It is worth noting that the last double bond of these PUFAs, i.e., omega 6 in AA or omega 3 in EPA and DHA, respectively, was preferentially epoxidized. In this study, we have characterized the stereoselectivity of this epoxidation reaction by comparison with the PUFA-LC epoxide stereoisomers obtained from the enantioselective bacterial CYP102A1 F87V. The stereoselectivity of the epoxidation of the last olefin of AA (omega 6), EPA (omega 3), or DHA (omega 3) differed between the CYP isoforms but was similar for EPA and DHA. These data give additional insight into the PUFA-LC epoxide enantiomers generated by the hepatic CYPs.-Lucas, D., S. Goulitquer, J. Marienhagen, M. Fer, Y. Dreano, U. Schwaneberg, Y. Amet, and L. Corcos. Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450. J. Lipid Res. 2010. 51: 1125-1133.

  DOI：

  10.1194/jlr.m003061

文献信息

• Lyophilized extracts from vegetable flours as valuable alternatives to purified oxygenases for the synthesis of oxylipins
  作者：Claudia Sanfilippo、Angela Paterna、Daniela M. Biondi、Angela Patti

  DOI：10.1016/j.bioorg.2019.103325

  日期：2019.12

  flour and oat flour have been used as valuable alternatives to purified oxygenase enzymes for the preparation of oxylipins derived from (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid (EPA). The lipoxygenase activity in the aqueous extracts of soybean (Glycine max. L.) flour was monitored with linoleic acid as substrate and compared with the commercially available purified enzyme (LOX-1). Oat flour extracts

  在这项工作中，大豆粉和燕麦粉的全部水提取物已用作纯化加氧酶的有价值的替代品，用于制备衍生自（5Z，8Z，11Z，14Z，17Z）-二十碳五烯酸（EPA）的脂蛋白。在大豆的水提取物中的脂氧化酶活性（甘氨酸最大。 L.）面粉用亚油酸作为底物监测，并与可商购的纯化酶（LOX-1）进行比较。燕麦粉提取物（燕麦）通过比较在油酸甲酯的环氧化中的不同酶制剂来评估它们的过氧化酶活性。已经发现，从这些植物粉中冻干水提取物在酶稳定性，可再现性和对制备性有机合成的适用性方面具有优势。测试冻干的酶制剂对EPA的氧官能化，并以令人满意的产率分离所形成的产物。在大豆冻干提取物的存在下，EPA得到15 S-羟基-（5 Z，8 Z，11 Z，13 E，17 Z对映体形式的）-二十碳五烯酸为独家产品。燕麦粉中的过氧化酶的选择性较低，并催化了EPA的不同环氧化物的形成。然而，在五个条件下，在受控条件下进行EPA的生物催化环氧化可得到旋光性（17
• NOVEL EICOSANOID DERIVATIVES
  申请人：Schunck Wolf-Hagen

  公开号：US20120122972A1

  公开（公告）日：2012-05-17

  The present invention provides compounds (n-3 PUFA derivatives) of formula (I) that modulate conditions associated with cardiac damage, especially cardiac arrhythmias.

  本发明提供了公式（I）的化合物（n-3 PUFA衍生物），该化合物调节与心脏损伤有关的病症，特别是心律失常。
• Stable analogs of CYP450 lipid metabolites and inhibitors of soluble epoxide hydrolase
  申请人：Massachusetts Eye and Ear Infirmary

  公开号：US10758511B2

  公开（公告）日：2020-09-01

  This disclosure relates to methods of reducing inflammation, angiogenesis, vascular leakage and neovascularization by administering to a subject in need thereof one or more stable analogs of CYP450 lipid metabolites (e.g., eicosanoids) and one or more inhibitors of a soluble epoxide hydrolase (sEH). This disclosure also relates to methods of treating disorders associated with inflammation, angiogenesis, vascular leakage and neovascularization by administering to a subject in need thereof one or more stable analogs of CYP450 lipid metabolites (e.g., eicosanoids) and one or more inhibitors of a soluble epoxide hydrolase (sEH). This disclosure further relates to pharmaceutical compositions and kits comprising at least one stable analog of CYP450 lipid metabolites (e.g., eicosanoids) and at least one inhibitor of a soluble epoxide hydrolase (sEH).

  本公开涉及通过向有需要的受试者施用一种或多种CYP450脂质代谢物（如二十烷酸）的稳定类似物和一种或多种可溶性环氧化物水解酶（sEH）的抑制剂来减少炎症、血管生成、血管渗漏和新生血管的方法。本公开还涉及通过向有需要的受试者施用一种或多种 CYP450 脂质代谢物（如二十烷酸）的稳定类似物和一种或多种可溶性环氧化物水解酶（sEH）抑制剂来治疗与炎症、血管生成、血管渗漏和新生血管有关的疾病的方法。本公开进一步涉及药物组合物和试剂盒，其中包含至少一种 CYP450 脂类代谢物（如二十烷酸）的稳定类似物和至少一种可溶性环氧化物水解酶（sEH）的抑制剂。
• Methods of inhibiting pain
  申请人：The Regents of the University of California

  公开号：US10813894B2

  公开（公告）日：2020-10-27

  Provided are methods and compositions for preventing, reducing, mitigating and treating pain, particularly neuropathic pain by the combined administration of an agent that increases EETs and an agent that reduces/inhibits endoplasmic reticulum (ER) stress.

  本文提供了通过联合施用增加 EETs 的制剂和减少/抑制内质网（ER）应激的制剂来预防、减少、减轻和治疗疼痛，特别是神经性疼痛的方法和组合物。
• EP2607358
  申请人：——

  公开号：——

  公开（公告）日：——