15S-hydroperoxy-11Z,13E-eicosadienoic acid

• 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: 15S-hydroperoxy-11Z,13E-eicosadienoic acid
• 英文别名: 15-(S)-HPEDA；15(S)-HpEDE；(11Z,13E,15S)-15-hydroperoxyicosa-11,13-dienoic acid
• 化学式: C₂₀H₃₆O₄
• 分子量: 340.503
• InChiKey: KEXNVBSLXJLOPR-XMSPSUPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  24
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  15S-hydroperoxy-11Z,13E-eicosadienoic acid 在 sodium tetrahydroborate 作用下， 生成 15-(S)-HEDA
  参考文献：
  名称：

  Structural requirements for the inhibition of 5-lipoxygenase by 15-hydroxyeicosa-5,8,11,13-tetraenoic acid analogs

  摘要：

  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.

  DOI：

  10.1021/jm00385a005
• 作为产物：
  描述：

  高-gamma-亚油酸 在 硫酸氢铵 作用下， 生成 15S-hydroperoxy-11Z,13E-eicosadienoic acid
  参考文献：
  名称：

  Structural requirements for the inhibition of 5-lipoxygenase by 15-hydroxyeicosa-5,8,11,13-tetraenoic acid analogs

  摘要：

  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.

  DOI：

  10.1021/jm00385a005

文献信息

• 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。
• US9670126B2
  申请人：——

  公开号：US9670126B2

  公开（公告）日：2017-06-06
• 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.