(11R)-<11-(2)H>octadeca-9(Z),12(Z)-dienoic acid | 144401-59-2

• 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: (11R)-<11-(2)H>octadeca-9(Z),12(Z)-dienoic acid
• 英文别名: 11(R)-deutero linoleic acid；(11R)-(11-(2)H)octadeca-9(Z),12(Z)-dienoic acid
• CAS: 144401-59-2
• 化学式: C₁₈H₃₂O₂
• 分子量: 281.443
• InChiKey: OYHQOLUKZRVURQ-GPIQSODVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.88
• 重原子数：
  20.0
• 可旋转键数：
  14.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  37.3
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 (11R)-<11-(2)H>octadeca-9(Z),12(Z)-dienoic acid 以 乙醚 为溶剂， 以81%的产率得到methyl (11R)-<11-(2)H>octadeca-9(Z),12(Z)-dienoate
  参考文献：
  名称：

  Synthesis of linoleic acid with chiral isotopic labelling at a flanking and a medial allylic methylene: the (8R,9Z,12Z)-[8-2H] and (11R,9Z,12Z)-[11-2H]-stereoisomers, and (Z)-[2,2-2H2]non-3-enal

  摘要：

  [1-H-2]Oct-2-ynal is converted by fermenting bakers' yeast into (1S)-[1-H-2]oct-2-yn-l-ol with an enantiomeric purity of > 96% as measured by Mosher's MTPA method. The alcohol, as its tosyl ester, was then converted by copper-catalysed coupling with the di-Grignard of dec-9-ynoic acid and catalytic semi-hydrogenation, into (11R)-[11-H-2]linoleic acid having less than 2% E-material and >95 atom %D. Provision for (11S)-[11-H-2]linoleic acid was made by configurational inversion of (1R) - [1-H-2]oct-2-yn-1-ol using Mitsunobu chemistry. (8R)-[8-H-2]Linoleic acid is made by a similar approach, the labelled chiral centre being formed on (8S)-8-hydroxy-[8-H-2]octanoic acid (> 96% ee). Reaction of the corresponding tosate with lithium acetylide-ethylenediamine complex gave, with configurational inversion, (8R)-[8-H-2]dec-9-ynoic acid, built into (8R)-[8-H-2]linoleic acid. A degradative circuit is applied to estimate the extent of configurational inversion in the displacement. Mitsunobu inversion of the (8S)-8-hydroxy compound provides access to (8S)-[8-H-2]linoleic acid. (Z)-Non-3-enal, a labile aldehyde from the enzymic degradation of linoleic acid, is made in [2,2-H-2(2)]-labelled form by a synthesis which uses, as a key step, the reaction between triheptynylborane and deuteriodiazoacetic ester.

  DOI：

  10.1039/p19920001929
• 作为产物：
  描述：

  9-癸炔酸 在 喹啉 、 Lindlar's catalyst 、 copper(I) bromide dimethylsulfide complex 乙基溴化镁 、 氢气 作用下， 以 正己烷 为溶剂， 反应 10.83h， 生成 (11R)-<11-(2)H>octadeca-9(Z),12(Z)-dienoic acid
  参考文献：
  名称：

  Synthesis of linoleic acid with chiral isotopic labelling at a flanking and a medial allylic methylene: the (8R,9Z,12Z)-[8-2H] and (11R,9Z,12Z)-[11-2H]-stereoisomers, and (Z)-[2,2-2H2]non-3-enal

  摘要：

  [1-H-2]Oct-2-ynal is converted by fermenting bakers' yeast into (1S)-[1-H-2]oct-2-yn-l-ol with an enantiomeric purity of > 96% as measured by Mosher's MTPA method. The alcohol, as its tosyl ester, was then converted by copper-catalysed coupling with the di-Grignard of dec-9-ynoic acid and catalytic semi-hydrogenation, into (11R)-[11-H-2]linoleic acid having less than 2% E-material and >95 atom %D. Provision for (11S)-[11-H-2]linoleic acid was made by configurational inversion of (1R) - [1-H-2]oct-2-yn-1-ol using Mitsunobu chemistry. (8R)-[8-H-2]Linoleic acid is made by a similar approach, the labelled chiral centre being formed on (8S)-8-hydroxy-[8-H-2]octanoic acid (> 96% ee). Reaction of the corresponding tosate with lithium acetylide-ethylenediamine complex gave, with configurational inversion, (8R)-[8-H-2]dec-9-ynoic acid, built into (8R)-[8-H-2]linoleic acid. A degradative circuit is applied to estimate the extent of configurational inversion in the displacement. Mitsunobu inversion of the (8S)-8-hydroxy compound provides access to (8S)-[8-H-2]linoleic acid. (Z)-Non-3-enal, a labile aldehyde from the enzymic degradation of linoleic acid, is made in [2,2-H-2(2)]-labelled form by a synthesis which uses, as a key step, the reaction between triheptynylborane and deuteriodiazoacetic ester.

  DOI：

  10.1039/p19920001929

文献信息

• Topological Study of Mechanistic Diversity in Conjugated Fatty Acid Biosynthesis
  作者：Palash Bhar、Darwin W. Reed、Patrick S. Covello、Peter H. Buist

  DOI：10.1002/anie.201202080

  日期：2012.7.2

  Variations on an oxidative theme: The precision with which FAD2‐type desaturases carry out CH activation reactions on flexible lipidic substrates is astonishing. The conformational space available within the active site of these enzymes has been explored using deuterium‐labeled substrates, and evidence for a novel quasi‐eclipsed conformer has been uncovered. The scheme shows some prototypical substrate

  氧化主题的变化：FAD2型去饱和酶在柔性脂质底物上进行CH活化反应的精度令人惊讶。已经使用氘标记的底物探索了这些酶活性位点中可用的构象空间，并且已经发现了新的半蚀构象异构体的证据。该方案显示了一些原型底物构象。
• Mutations of Triad Determinants Changes the Substrate Alignment at the Catalytic Center of Human ALOX5
  作者：Igor Ivanov、Alexey B. Golovanov、Cristián Ferretti、Miquel Canyelles-Niño、Dagmar Heydeck、Sabine Stehling、José M. Lluch、Àngels González-Lafont、Hartmut Kühn

  DOI：10.1021/acschembio.9b00674

  日期：2019.12.20

  arachidonic acid mainly to 5(S)-hydroperoxyeicosatetraenoic acid (HpETE). In contrast, 15(S)- and 8(S)-H(p)ETE were formed by the mutant enzyme. In addition to arachidonic acid, wild-type ALOX5 accepted eicosapentaenoic acid (EPA) as substrate, but C18 fatty acids were not oxygenated. The quadruple mutant also accepted linoleic acid and α- and γ-linolenic acid as substrate. Structural analysis of the

  对于不同哺乳动物的ALOX15直系同源物的特异性，氨基酸Phe353，Ile418，Met419和Ile593（“三联决定簇”）的几何形状很重要，这些残基的诱变改变了这些酶的反应特异性。在这里，我们在Sf9昆虫细胞中表达了野生型人ALOX5及其F359W / A424I / N425M / A603I突变体，并表征了这两种酶变体的催化差异。我们发现野生型ALOX5主要将花生四烯酸转化为5（S）-氢过氧二十碳四烯酸（HpETE）。相反，由突变酶形成15（S）-和8（S）-H（p）ETE。除花生四烯酸外，野生型ALOX5还接受二十碳五烯酸（EPA）作为底物，但C18脂肪酸未被氧化。该四重突变体还接受亚油酸以及α-和γ-亚麻酸作为底物。氧化产物的结构分析和立体定向标记的11（S）-和11（R）-氘代亚油酸的动力学研究表明了活性位点上底物取向的替代方法。在计算机对接研究中，分子动力学模拟和量子力学/分子力学（QM