(8Z,11Z,13E,15R)-15-羟基-8,11,13-二十碳三烯酸 | 92693-02-2

• 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: (8Z,11Z,13E,15R)-15-羟基-8,11,13-二十碳三烯酸
• 英文名称: 15(S)-HETrE
• 英文别名: 15(S)-hydroxyeicosatrienoic acid；15S-hydroxy-8Z,11Z,13E-eicosatrienoic acid；(8Z,11Z,13E,15S)-15-hydroxyicosa-8,11,13-trienoic acid
• CAS: 92693-02-2
• 化学式: C₂₀H₃₄O₃
• 分子量: 322.488
• InChiKey: IUKXMNDGTWTNTP-OAHXIXLCSA-N

物化性质

• 沸点：
  487.4±40.0 °C(Predicted)
• 密度：
  0.971±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

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  23
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2918199090
• 储存条件：
  -20°C，密闭保存，置于干燥处

制备方法与用途

(15-S)-HETrE是人中性粒细胞PMNL中的5-LO抑制剂，其IC50值为4.6 μM。

反应信息

• 作为反应物：
  描述：

  L-赖氨酸 、 (8Z,11Z,13E,15R)-15-羟基-8,11,13-二十碳三烯酸 以 甲醇 、 乙酸乙酯 为溶剂， 生成 15-(S)-HETrE L-lysine salt
  参考文献：
  名称：

  [EN] PHARMACEUTICALLY ACCEPTABLE SALTS OF POLYUNSATURATED HYDROXY FATTY ACIDS
  [FR] SELS ACCEPTABLES SUR LE PLAN PHARMACEUTIQUE D'ACIDES GRAS HYDROXYLÉS POLYINSATURÉS

  摘要：

  本公开提供了15-脂氧合酶产物的药用可接受的稳定盐形式，例如15-HETrE赖氨酸盐，包括相同盐的组合物以及制备和使用相同盐的方法。

  公开号：

  WO2015071766A1
• 作为产物：
  描述：

  顺式-8,11,14-二十烷三烯酸甲酯 在 硼酸三钠 、 L-半胱氨酸 、 氧气 作用下， 以 水 为溶剂， 5.0 ℃ 、250.0 kPa 条件下， 反应 2.0h， 生成 (8Z,11Z,13E,15R)-15-羟基-8,11,13-二十碳三烯酸
  参考文献：
  名称：

  [EN] PHARMACEUTICALLY ACCEPTABLE SALTS OF POLYUNSATURATED HYDROXY FATTY ACIDS
  [FR] SELS ACCEPTABLES SUR LE PLAN PHARMACEUTIQUE D'ACIDES GRAS HYDROXYLÉS POLYINSATURÉS

  摘要：

  本公开提供了15-脂氧合酶产物的药用可接受的稳定盐形式，例如15-HETrE赖氨酸盐，包括相同盐的组合物以及制备和使用相同盐的方法。

  公开号：

  WO2015071766A1

文献信息

• Asymmetric synthesis of unnatural (Z,Z,E)-octadecatrienoid and eicosatrienoid by lipoxygenase-catalyzed oxygenation
  作者：S. Nanda、J.S. Yadav

  DOI：10.1016/s0957-4166(03)00369-0

  日期：2003.7

  The asymmetric synthesis of unnatural 13-hydroxy-(6Z,9Z,11E,13S)-octadecatrienoid and 15-hydroxy-(8Z,11Z,13E,15S)-eicosatrienoid is described using a biomimetic oxidation route. The main highlights of this synthesis are the asymmetric hydroxylation of the substrate with soybean lipoxygenase and cis selective Wittig olefination.

  使用仿生氧化描述了不自然的13-羟基-（6 Z，9 Z，11 E，13 S）-十八碳三烯化合物和15-羟基-（8 Z，11 Z，13 E，15 S）-二十碳三烯化合物的不对称合成路线。该合成的主要亮点是大豆脂氧合酶对底物的不对称羟基化和顺式选择性维蒂希烯化。
• METHODS OF MAKING 15-HYDROXY FATTY ACID DERIVATIVES
  申请人：Dignity Sciences Limited

  公开号：US20150119593A1

  公开（公告）日：2015-04-30

  The present disclosure provides methods of making 15-hydroxy fatty acid derivatives, such as 15-(S)-hydroxyeicosatrienoic acid (HETrE or 15-(S)-HETrE) or 15(S)-hydroxyeicosapentaenoic acid (HEPE or 15(S)-HEPE) from the corresponding fatty acid (e.g., dihomo-γ-linolenic acid (DGLA) or eicosapentaenoic acid (EPA), respectively). In some embodiments, the method comprises contacting the fatty acid with an oxidizing agent (e.g., a lipoxygenase and oxygen) in the presence of a reducing agent (e.g., cysteine) to form the 15-hydroxy fatty acid derivatives in a single reaction vessel.

  本公开提供制备15-羟基脂肪酸衍生物的方法，例如制备15-(S)-羟基二十碳三烯酸（HETrE或15-(S)-HETrE）或15(S)-羟基二十碳五烯酸（HEPE或15(S)-HEPE）从相应的脂肪酸（例如二十二碳六烯酸（DGLA）或二十碳五烯酸（EPA））。在某些实施例中，该方法包括在单个反应容器中将脂肪酸与氧化剂（例如脂肪酸过氧化酶和氧气）在还原剂（例如半胱氨酸）的存在下接触，以形成15-羟基脂肪酸衍生物。
• Differential diagnosis of liver disease
  申请人：The Regents of the University of California

  公开号：US10422786B2

  公开（公告）日：2019-09-24

  The present invention relates to the substantially non-invasive diagnosis of liver disease, especially to enable intervention in the progression of such disease at an early stage. This invention further relates to the use of plasma biomarkers to differentiate nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver (NAFL) and non-nonalcoholic fatty liver disease (NAFLD), and normal controls. Specifically, the invention relates to the use of free eicosanoids and other polyunsaturated fatty acid (PUFA) metabolite levels in plasma to differentiate NASH from NAFL and non-NAFLD normal controls.

  本发明涉及肝脏疾病的基本无创诊断，特别是能够在早期阶段对此类疾病的进展进行干预。本发明进一步涉及使用血浆生物标志物来区分非酒精性脂肪性肝炎（NASH）与非酒精性脂肪肝（NAFL）和非酒精性脂肪肝（NAFLD）以及正常对照组。具体来说，本发明涉及利用血浆中游离二十烷酸和其他多不饱和脂肪酸（PUFA）代谢物水平来区分非酒精性脂肪性肝炎（NASH）和非酒精性脂肪性肝病（NAFL）以及非酒精性脂肪性肝病（NAFLD）正常对照组。
• Compositions and methods for improving skin health and for the treatment and prevention of diseases, disorders and conditions associated with pathogenic microbes
  申请人：DermBiont, Inc.

  公开号：US11040077B2

  公开（公告）日：2021-06-22

  Disclosed herein are compositions and methods for using human-derived Janthinobacterium lividum. Compositions improve skin health. Methods may include applying human-derived Janthinobacterium lividum over a host or host area, such as skin or mucosa, to minimize the presence of one or more microbes, maximize therapeutic effects, and/or improve health. A method to minimize a pathogenic microbe may include applying to a surface a composition including human-derived Janthinobacterium lividum and an acceptable carrier. Compositions and methods may include a prebiotic to maximize growth and/or metabolites. Compositions and methods may include human-derived Janthinobacterium lividum metabolites, such as violacein, prodigiosin, indole-3-carboxaldehyde, and lantibiotics, and/or other Postbiotics.

  本文公开了使用源自人类的 Lividum Janthinobacterium 的组合物和方法。组合物可改善皮肤健康。方法可包括在宿主或宿主区域（如皮肤或粘膜）上施用源于人的生发的Lividum Janthinobacterium，以最大限度地减少一种或多种微生物的存在，最大限度地提高治疗效果，和/或改善健康状况。减少病原微生物的方法可包括向表面施用一种组合物，该组合物包括来源于人类的Janthinobacterium lividum和一种可接受的载体。组合物和方法可包括益生元，以最大限度地提高生长和/或代谢物。组合物和方法可包括来源于人的猪蓝细菌代谢物，如violacein、prodigiosin、吲哚-3-甲醛、兰特益生菌和/或其他后益生菌。
• Structural requirements for the inhibition of 5-lipoxygenase by 15-hydroxyeicosa-5,8,11,13-tetraenoic acid analogs
  作者：Fortuna Haviv、James D. Ratajczyk、Robert W. DeNet、Yvonne C. Martin、Richard D. Dyer、George W. Carter

  DOI：10.1021/jm00385a005

  日期：1987.2

  The structural requirements for inhibition of RBL-1 (rat basophilic leukemia) 5-lipoxygenase by 15-hydroxyeicosa-5,8,11,13-tetraenoic acid (15-HETE, 1) were studied by systematic chemical modifications of the molecule at the hydroxyl and carboxyl groups, the double bonds, and the carboxylate and omega side chains. The most potent inhibitors were analogues that contained a 5,8-cis,cis-diene system and acted as alternate substrates for the enzyme. However, several analogues in which the 5,8-diene had been reduced were also found to inhibit the enzyme. Inhibition of 5-lipoxygenase by 15-hydroxyeicosa-11,13-dienoic acid (15-HEDE) analogues was optimal in compounds that generally contained a free carboxyl group, a carboxylate side chain of nine carbons, an omega side chain of five or six carbons, a cis,trans- or trans,cis-11,13-diene or 11,13-diyne system, and a 15-hydroxyl group. Conversion of 15-HEDE to its 16-membered lactone reduced but did not eliminate 5-lipoxygenase inhibitory activity. In contrast, a 3- to 10-fold enhancement of activity occurred when 5,15-diHETE (58) or 5-HETE (56) were cyclized to their respective delta-lactones. Molecular modeling of 15-HEDE analogues, modified in the C11-C15 region, showed that inactive analogues protrude into regions in space not occupied by active analogues. These structural studies indicate that multiple regions are important for 5-lipoxygenase inhibition by both 15-HETE and 15-HEDE analogues and that no single region plays a predominant role in inhibition.