5(S)-羟化二十烷四烯酸 | 330796-62-8

• 物质功能分类: 生物 - 细胞培养 - 添加剂
• 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: 5(S)-羟化二十烷四烯酸
• 英文名称: 5(S)-HETE
• 英文别名: 5-HETE；5-hydroxyeicosatetraenoic acid；5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid；5S-hydroxyeicosatetraenoic acid；(5S,6E,8Z,11Z,14Z)-5-hydroxyicosa-6,8,11,14-tetraenoic acid
• CAS: 330796-62-8；70608-72-9
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: KGIJOOYOSFUGPC-JGKLHWIESA-N

物化性质

• 沸点：
  487.7±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
• 物理描述：
  Solid
• 碰撞截面：
  188.21 Ų [M+Na]+ [CCS Type: DT, Method: stepped-field]

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 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

反应信息

• 作为反应物：
  描述：

  5(S)-羟化二十烷四烯酸 在 苯酚 Tris-HCl buffer 、 hematin 、 human COX-2 作用下， 以 甲醇 为溶剂， 反应 0.08h， 生成 5S,15S-dihydroxy-9S,11R;8S,12S-diperoxy-6E,13E-eicosadienoic acid
  参考文献：
  名称：

  Convergent Oxygenation of Arachidonic Acid by 5-Lipoxygenase and Cyclooxygenase-2

  摘要：

  5-Lipoxygenase and cyclooxygenase-2 (COX-2) initiate the biosynthesis of distinct families of mediators from arachidonic acid (leukotrienes and prostaglandins, respectively) and are each the target of anti-inflammatory medications. Here we show that the product of 5-lipoxygenase, 5S-hydroxyeicosatetraenoic acid, is selectively and efficiently triply oxygenated by COX-2, implicating a cross-pathway interaction. The product is a unique diendoperoxide, potentially representing the parent compound of a novel group of lipid mediators.

  DOI：

  10.1021/ja056517y
• 作为产物：
  描述：

  花生四烯酸 在 脂肪氧化酶 、 三苯基膦 作用下， 生成 5(S)-羟化二十烷四烯酸
  参考文献：
  名称：

  COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes

  摘要：

  Biosynthesis of 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) in leukocytes involves consecutive oxygenation of arachidonic acid by 5-lipoxygenase (LOX) and 15-LOX in either order. Here, we analyzed the contribution of cyclooxygenase (COX)-2 to the biosynthesis of 5,15-di-HETE and 5,11-diHETE in isolated human leukocytes activated with lipopolysaccharide and calcium ionophore A23187. Transformation of arachidonic acid was initiated by 5-LOX providing 5S-HETE as a substrate for COX-2 forming 5S,15S-diHETE, 5S,15R-diHETE, and 5S,11R-di-HETE as shown by LC/MS and chiral phase HPLC analyses. The levels of 5,15-diHETE were 0.45 +/- 0.2 ng/10(6) cells (mean +/- SEM, n = 6), reaching about half the level of LTB(4) (1.3 +/- 0.5 ng/10(6) cells, n = 6). The COX-2 specific inhibitor NS-398 reduced the levels of 5,15-diHETE to below 0.02 ng/10(6) cells in four of six samples. Similar reduction was achieved by MK-886, an inhibitor of 5-LOX activating protein but the above differences were not statistically significant. Aspirin treatment of the activated cells allowed formation of 5,15-diHETE (0.1 +/- 0.05 ng/10(6) cells, n = 6) but, as expected, abolished formation of 5,11-diHETE. The mixture of activated cells also produced 5S,12S-diHETE with the unusual 6E,8Z,10E double bond configuration, implicating biosynthesis by 5-LOX and 12-LOX activity rather than by hydrolysis of the leukotriene A(4)-epoxide. Exogenous octadeuterated 5S-HETE and 15S-HETE were converted to 5,15-diHETE, implicating that multiple oxygenation pathways of arachidonic acid occur in activated leukocytes. The contribution of COX-2 to the biosynthesis of dihydroxylated derivatives of arachidonic acid provides evidence for functional coupling with 5-LOX in activated human leukocytes.-Tejera, N., W. E. Boeglin, T. Suzuki, and C. Schneider. COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes. J. Lipid Res. 2012. 53: 87-94.

  DOI：

  10.1194/jlr.m017822

文献信息

• Improved Sensitivity Mass Spectrometric Detection of Eicosanoids by Charge Reversal Derivatization
  作者：James G. Bollinger、Wallace Thompson、Ying Lai、Rob C. Oslund、Teal S. Hallstrand、Martin Sadilek、Frantisek Turecek、Michael H. Gelb

  DOI：10.1021/ac100720p

  日期：2010.8.15

  eicosanoids to a cationic AMPP amide improves sensitivity of detection by 10- to 20-fold compared to negative mode electrospray ionization detection of underivatized analytes. This charge reversal derivatization allows detection of cations rather than anions in the electrospray ionization mass spectrometer, which enhances sensitivity. Another factor is that AMPP amides undergo considerable collision-induced dissociation

  液相色谱-电喷雾电离-串联质谱联用 (LC-ESI-MS/MS) 是一种分析多不饱和脂肪酸（包括类二十烷酸）含氧代谢物的强大方法。这里我们描述了一种新的衍生化试剂N的合成-(4-氨基甲基苯基)吡啶鎓 (AMPP)，可通过酰胺键以定量产率与类二十烷酸偶联。与未衍生化分析物的负模式电喷雾电离检测相比，将类二十烷酸的羧酸转化为阳离子 AMPP 酰胺可将检测灵敏度提高 10 到 20 倍。这种电荷反转衍生允许在电喷雾电离质谱仪中检测阳离子而不是阴离子，从而提高灵敏度。另一个因素是 AMPP 酰胺在分析物部分而不是仅在阳离子标签部分发生相当大的碰撞诱导解离，这使得同量异位衍生物可以通过串联质谱法进行区分，这进一步提高了灵敏度和特异性。这种简单的衍生方法允许前列腺素，2、白三烯B 4、羟基二十碳四烯酸异构体和花生四烯酸在复杂生物样品中定量，定量限在200-900 fg范围内。可以预期，AMPP 衍生化
• Pharmacokinetics and Metabolism of Selective Oxoeicosanoid (OXE) Receptor Antagonists and Their Effects on 5-Oxo-6,8,11,14-eicosatetraenoic Acid (5-Oxo-ETE)-Induced Granulocyte Activation in Monkeys
  作者：Chantal Cossette、Shishir Chourey、Qiuji Ye、Chintam Nagendra Reddy、Vivek Gore、Sylvie Gravel、Irina Slobodchikova、Dajana Vuckovic、Joshua Rokach、William S. Powell

  DOI：10.1021/acs.jmedchem.6b00895

  日期：2016.11.23

  rodents. We previously reported that the indole 230 is a potent human OXE receptor antagonist. The objective of the present study was to determine whether the monkey would be a suitable animal model to investigate its pharmaceutical potential. We found that monkey leukocytes synthesize and respond to 5-oxo-ETE and that 230 is a potent antagonist of the OXE receptor in monkey eosinophils. Pharmacokinetic

  有效的嗜酸性粒细胞趋化剂5-oxo-6,8,11,14-二十碳四烯酸（5-oxo-ETE）是一种5-脂氧合酶产物，其通过选择性OXE受体起作用，该受体存在于许多物种中，但不包括啮齿类动物。我们先前曾报道过吲哚230是一种有效的人类OXE受体拮抗剂。本研究的目的是确定猴子是否适合作为研究其药物潜力的动物模型。我们发现猴子白细胞合成并响应5-oxo-ETE，而230是猴子嗜酸性粒细胞中OXE受体的有效拮抗剂。药代动力学研究表明230口服后迅速出现在血液中。使用化学合成的标准品，我们确定了230个主要的微粒体和血浆代谢物为烷基侧链的ω2-羟基化产物。这些研究表明，猴子是研究OXE受体拮抗剂潜在药物的有前途的动物模型。
• Reagent and method for detection of carboxylic acids by mass spectrometry
  申请人：Gelb Michael H.

  公开号：US09045421B2

  公开（公告）日：2015-06-02

  Method and reagent for converting a carboxylic acid to a positively charge amide are described. The method and reagent facilitate positive ion mass spectral analysis of carboxylic acids. The method includes reacting a carboxylic acid with a compound having formula I: wherein A and B are aromatic rings, ring A includes a quaternized nitrogen and has n additional ring atoms, each additional ring atom optionally substituted with an RA group, and n is an integer from 4 to 10, and ring B includes a carbon atom and has m additional ring atoms, each additional ring atom optionally substituted with an RB group, and m is an integer from 4 to 10. The compound includes at least one RA or RB group, and the at least one RA and RB group is -L-N(Z)H; and X− is a counterion.

  描述了将羧酸转化为带正电荷的酰胺的方法和试剂。该方法和试剂有助于对羧酸进行正离子质谱分析。该方法包括将羧酸与具有以下式I的化合物反应：其中A和B为芳香环，环A包括一个季铵氮，并且具有n个额外的环原子，每个额外的环原子可选择地被RA基取代，n为4至10之间的整数，环B包括一个碳原子，并具有m个额外的环原子，每个额外的环原子可选择地被RB基取代，m为4至10之间的整数。该化合物包括至少一个RA或RB基，至少一个RA和RB基为-L-N(Z)H；X-为一个对离子。
• A General Strategy for the Synthesis of Monohydroxy-eicosatetraenoic Acids: Total Synthesis of 5(<i>S</i>)-Hydroxy-6(<i>E</i>),8,11,14(<i>Z</i>)-eicosatetraenoic Acid (5-HETE) and 12(<i>S</i>)-Hydroxy-5,8,14(<i>Z</i>), 10(<i>E</i>)-eicosatetraenoic Acid (12-HETE)
  作者：K. C. Nicolaou、T. Ladduwahetty、I. M. Taffer、R. E. Zipkin

  DOI：10.1055/s-1986-31612

  日期：——

  Stereocontrolled total syntheses of 5(S)-hydroxy-6(E),8, 11,14(Z)-eicosatetraenoic acid (5-HETE) and 12(S)hydroxy-5,8,14 (Z), 10(E)-eicosatetraenoic acid (12-HETE) via palladium(0)-copper(I) coupling technology are described.

  通过钯(0)-铜(I)耦合技术合成5(S)-羟基-6(E),8, 11,14(Z)-二十碳四烯酸（5-HETE）和12(S)-羟基-5,8,14(Z), 10(E)-二十碳四烯酸（12-HETE）的立体选择性全合成过程被描述。
• Stereospecific Total Synthesis of Dimorphecolic Acid, 5(S)-HETE, and 12(S)-HETE
  作者：Toshiyuki Shimazaki、Yuichi Kobayashi、Fumie Sato

  DOI：10.1246/cl.1988.1785

  日期：1988.10.5

  First enantiospecific synthesis of dimorphecolic acid is accomplished via an efficient and stereocontrolled route. The convenient synthesis of 5(S)-HETE and 12(S)-HETE is also described.

  二吗啡酸的首次对映特异性合成是通过一种有效且立体控制的途径完成的。还描述了 5(S)-HETE 和 12(S)-HETE 的方便合成。