18-hydroxyeicosatetraenoic acid | 133268-58-3

• 物质功能分类: 生物化工 - 生化试剂
• 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: 18-hydroxyeicosatetraenoic acid
• 英文别名: 18-hydroxyarachidonic acid；18-HETE；(5Z,8Z,11Z,14Z)-18-Hydroxyicosa-5,8,11,14-tetraenoic acid
• CAS: 133268-58-3
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: PPCHNRUZQWLEMF-XBOCNYGYSA-N

物化性质

• 沸点：
  477.3±45.0 °C(Predicted)
• 密度：
  0.984±0.06 g/cm3(Predicted)
• 溶解度：
  0.1 M Na2CO3：2 mg/mL； DMF：可混溶； DMSO：可混溶；乙醇：可混溶； PBS（pH 7.2）：0.8 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

18-烃基二十烷酸是花生酸的一种已知人类代谢物。

18-HETE is a known human metabolite of arachidonic acid.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  18-hydroxyeicosatetraenoic acid 在 吡啶 、 sodium azide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.5h， 生成 (5Z,8Z,11Z,14Z)-18-azidoeicosa-5,8,11,14-tetraenoic acid
  参考文献：
  名称：

  Synthesis of (5Z,8Z,11Z,14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-3H8]-analogues through a common synthetic route

  摘要：

  Total synthesis of (5Z,8Z, 11Z, 14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-H-3(8)]-analogues via the corresponding p-toluenesulphonates is reported. This synthetic approach allows the preparation of radioactively labelled arachidonic acid derivatives following a common synthetic route. Activity assays indicated that 15-lipoxygenases may tolerate the azido group in the substrate binding pocket and thus, radioactively labelled azido compounds may be used as photo-affinity probes to investigate mechanistic features of eicosanoid biosynthesis. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

  DOI：

  10.1016/j.chemphyslip.2004.02.008
• 作为产物：
  描述：

  1-氯-3-戊醇 在 吡啶 、 喹啉 、 sodium hydroxide 、 copper(l) iodide 、 正丁基锂 、 四溴化碳 、 四丁基氟化铵 、 氢气 、 potassium carbonate 、 三苯基膦 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 苯 为溶剂， 反应 47.58h， 生成 18-hydroxyeicosatetraenoic acid
  参考文献：
  名称：

  Total synthesis of (5Z,8Z,11Z,14Z)-18- and 19-oxoeicosa-5,8,11,14-tetraenoic acids

  摘要：

  8-oxo-ETE was synthesized via the corresponding tetraacetylenic precursor, which was prepared by cross-coupling of three key synthons: methyl 5-hexynoate, the bisfunctional C-7-C-13 fragment-7-bromo-2,5-heptadiyne-l-ol and rac-3-(benzoyloxy)hept-6-yn. The carbonyl function was introduced at the last synthesis step. 19-oxo-ETE was synthesized by coupling of acid anhydride, prepared from monomethyl ester of(5Z,8Z,l IZ,14Z)-nonadeca-5,8,11,14-tetraen-1,19-dioic acid, either with lithium dimethylcuprate or methylcuprate in a one-step procedure. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(02)01029-3

文献信息

• Repurposing Resveratrol and Fluconazole To Modulate Human Cytochrome P450-Mediated Arachidonic Acid Metabolism
  作者：Ahmed A. El-Sherbeni、Ayman O. S. El-Kadi

  DOI：10.1021/acs.molpharmaceut.5b00873

  日期：2016.4.4

  Cytochrome P450 (P450) enzymes metabolize arachidonic acid (AA) to several biologically active epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs). Repurposing clinically-approved drugs could provide safe and readily available means to control EETs and HETEs levels in humans. Our aim was to determine how to significantly and selectively modulate P450-AA metabolism in humans by

  细胞色素P450（P450）酶将花生四烯酸（AA）代谢为几种具有生物活性的环氧二十碳三烯酸（EET）和羟基二十碳四烯酸（HETE）。重新使用经过临床批准的药物可以为控制人类中的EET和HETE水平提供安全且容易获得的手段。我们的目标是确定如何通过临床批准的药物显着和选择性地调节人体内的P450-AA代谢。液相色谱-质谱法用于测定人重组P450酶以及人肝和肾微粒体形成的15种AA代谢产物。CYP2C19显示最高的EET形成活性，而CYP1B1和CYP2C8显示最高的中链HETE形成活性。CYP1A1和CYP4分别显示出最高的亚末端和20-HETE形成活性。与研究药物相比，白藜芦醇和氟康唑对肝P450-AA代谢产生了最有选择性和最显着的调节作用。蒙特卡洛模拟显示，每天服用2.5克后，有90％的人口在16-，18-和20-HETE形成中分别减少6-22％，16-39％和16-35％。白藜芦醇，氟康唑50
• LC–MS/MS analysis of epoxyalcohols and epoxides of arachidonic acid and their oxygenation by recombinant CYP4F8 and CYP4F22
  作者：T. Nilsson、I.V. Ivanov、E.H. Oliw

  DOI：10.1016/j.abb.2009.11.013

  日期：2010.2

  CYP4F22 and CYP4F8 are expressed in epidermis, and mutations of CYP4F22 are associated with lamellar ichthyosis. Epoxyalcohols (HEETs) and epoxides (EETs) of 20:4n-6 appear to be important for the water permeability barrier of skin. Our aim was to study the MS/MS spectra and fragmentation of these compounds and to determine whether they were oxidized by CYP4F22 or CYP4F8 expressed in yeast. HEETs were prepared from 1 5-hydroperoxyeicosatetraenoic acid (15-HPETE), 12-HPETE, and their- [H-2(8)]labeled isotopomers, and separated by normal phase-HPLC with MS/MS analysis. CYP4F22 oxygenated 20:4n-6 at C-I 8, whereas metabolites of HEETs could not be identified. CYP4F8 formed omega 3 hydroxy metabolites of HEETs derived from 12R-HPETE with 11,12-epoxy-10-hydroxy configuration, but not HEETs derived from 15S-HPETE. 8,9-EET and 11,12-EET were also subject to omega 3 hydroxylation by CYP4F8. We conclude that CYP4F8 and CYP4F22 oxidize 20:4n-6 and that CYP4F8 selectively oxidizes 8,9-EET, 11,12-EET, and 10, 11R, 12R-HEET at the omega 3 position. (C) 2010 Published by Elsevier Inc.
• General biochemical synthesis of oxygenated prostaglandins E
  作者：Charles J. Sih、Gabor Ambrus、Paul Foss、C. J. Lai

  DOI：10.1021/ja01041a065

  日期：1969.6
• Pseudomonas aeruginosa cytochrome P450 CYP168A1 is a fatty acid hydroxylase that metabolizes arachidonic acid to the vasodilator 19-HETE
  作者：Brian C. Tooker、Sylvie E. Kandel、Hannah M. Work、Jed N. Lampe

  DOI：10.1016/j.jbc.2022.101629

  日期：2022.3
• Synthesis of (5Z,8Z,11Z,14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-3H8]-analogues through a common synthetic route
  作者：Stepan G. Romanov、Igor V. Ivanov、Valery P. Shevchenko、Igor Yu. Nagaev、Alexandr A. Pushkov、Nikolai F. Myasoedov、Galina I. Myagkova、Hartmut Kuhn

  DOI：10.1016/j.chemphyslip.2004.02.008

  日期：2004.7

  Total synthesis of (5Z,8Z, 11Z, 14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-H-3(8)]-analogues via the corresponding p-toluenesulphonates is reported. This synthetic approach allows the preparation of radioactively labelled arachidonic acid derivatives following a common synthetic route. Activity assays indicated that 15-lipoxygenases may tolerate the azido group in the substrate binding pocket and thus, radioactively labelled azido compounds may be used as photo-affinity probes to investigate mechanistic features of eicosanoid biosynthesis. (C) 2004 Elsevier Ireland Ltd. All rights reserved.