12-hydroxydodecanoate | 17449-94-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: 12-hydroxydodecanoate
• 英文别名: 12-Hydroxylaurate
• CAS: 17449-94-4
• 化学式: C₁₂H₂₃O₃
• 分子量: 215.313
• InChiKey: ZDHCZVWCTKTBRY-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  15
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  12-hydroxydodecanoate 在 N-氯代丁二酰亚胺 、 2,2,6,6-四甲基哌啶氧化物 、 palladium 10% on activated carbon 、 四丁基溴化铵 、 甲酸铵 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 methyl 12-aminododecanoate
  参考文献：
  名称：

  [EN] PREPARATION OF AMINO ACIDS AND AMINO ACID DERIVATIVES
  [FR] PRÉPARATION D'ACIDES AMINÉS ET DE DÉRIVÉS D'ACIDES AMINÉS

  摘要：

  这项发明涉及一种合成氨基酸或氨基酸衍生物的方法，包括功能化烯烃的交叉复分解以及串联氨基化-还原过程。氨基酸和氨基酸衍生物具有许多有趣的物理和化学性质，在汽车、燃料、电子和纺织工业中找到了许多用途。

  公开号：

  WO2018057290A1
• 作为产物：
  描述：

  12-羟基十二酸 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 0.42h， 生成 12-hydroxydodecanoate
  参考文献：
  名称：

  Lactones. 2. Enthalpies of hydrolysis, reduction, and formation of the C4-C13 monocyclic lactones. Strain energies and conformations

  摘要：

  The enthalpies of hydrolysis of the monocyclic lactones from gamma-butyrolactone to tridecanolactone were determined calorimetrically, and the acyclic ethyl esters having the same number of atoms were studied in the same fashion. The enthalpies of reduction of the lactones to the corresponding alpha,omega-alkanediols with lithium triethylborohydride also were determined. The enthalpies of formation of the lactones and the ethyl esters were derived from these data. They were converted to values for the gas phase by measuring the enthalpies of vaporization of ethyl esters and of lactones. In the cases of gamma-butyrolactone and delta-valerolactone, the enthalpies of formation were in good accord with the previously reported values determined via combustion calorimetry. The strain energies of the lactones were obtained via isodesmic reactions. Valerolactone had a strain energy of 11 kcal/mol, and the largest strain energy was found with octanolactone (13 kcal/mol). The conformations of gamma-butyrolactone and delta-valerolactone were studied via MP2/6-31G* geometry optimizations, and the conformations of the other lactones were studied with use of the molecular mechanics program MM3. The energies of the lactones estimated via molecular mechanics were compared with the experimental results.

  DOI：

  10.1021/ja00020a036

文献信息

• Retinoids, ω-hydroxyfatty acids and cytotoxic aldehydes as physiological substrates, and H₂-receptor antagonists as pharmacological inhibitors, of human class IV alcohol dehydrogenase
  作者：Abdellah Allali-Hassani、Josep M Peralba、Sı́lvia Martras、Jaume Farrés、Xavier Parés

  DOI：10.1016/s0014-5793(98)00374-3

  日期：1998.4.24

  Kinetic constants of human class IV alcohol dehydrogenase (σσ‐ADH) support a role of the enzyme in retinoid metabolism, fatty acid ω‐oxidation, and elimination of cytotoxic aldehydes produced by lipid peroxidation. Class IV is the human ADH form most efficient in the reduction of 4‐hydroxynonenal (k cat/K m: 39 500 mM−1 min−1). Class IV shows high activity with all‐trans‐retinol and 9‐cis‐retinol,

  人类 IV 类酒精脱氢酶 (σσ-ADH) 的动力学常数支持该酶在类视黄醇代谢、脂肪酸 ω-氧化和消除脂质过氧化产生的细胞毒性醛中的作用。IV 类是还原 4-羟基壬烯醛最有效的人类 ADH 形式（k cat/K m：39 500 mM-1 min-1）。IV类对全反式-视黄醇和9-顺-视黄醇显示出高活性，而13-顺-视黄醇不是底物而是抑制剂。全反式视黄酸和 13-顺式视黄酸都是视黄醇氧化的有效竞争性抑制剂 (K i: 3–10 μM)，可作为调节视黄酸生成和 13 -顺式异构体。乙醇对 IV 类视黄醇氧化的抑制 (K i: 6-10 mM) 可能是乙醇毒性和致畸作用的起源。
• Characterization of pig kidney microsomal cytochrome <i>P</i>-450 catalysing 25-hydroxylation of vitamin D3 and C27 steroids
  作者：T Bergman、H Postlind

  DOI：10.1042/bj2700345

  日期：1990.9.1

  The cytochrome P-450 enzyme which catalyses 25-hydroxylation of vitamin D3 (cytochrome P-450(25] from pig kidney microsomes [Postlind & Wikvall (1988) Biochem. J. 253, 549-552] has been further purified. The specific content of cytochrome P-450 was 15.0 nmol.mg of protein-1, and the protein showed a single spot with an apparent isoelectric point of 7.4 and an Mr of 50,500 upon two-dimensional isoelectric-focusing/SDS/PAGE. The 25-hydroxylase activity towards vitamin D3 was 124 pmol.min-1.nmol of cytochrome P-450-1 and towards 1 alpha-hydroxyvitamin D3 it was 1375 pmol.min-1.nmol-1. The preparation also catalysed the 25-hydroxylation of 5 beta-cholestane-3 alpha,7 alpha-diol at a rate of 1000 pmol.min-1.nmol of cytochrome P-450-1 and omega-1 hydroxylation of lauric acid at a rate of 200 pmol.min-1.nmol of cytochrome P-450-1. A monoclonal antibody raised against the 25-hydroxylating cytochrome P-450, designated mAb 25E5, was prepared. After coupling to Sepharose, the antibody was able to bind to cytochrome P-450(25) from kidney as well as from pig liver microsomes, and to immunoprecipitate the activity for 25-hydroxylation of vitamin D3 and 5 beta-cholestane-3 alpha,7 alpha-diol when assayed in a reconstituted system. The hydroxylase activity towards lauric acid was not inhibited by the antibody. By SDS/PAGE and immunoblotting with mAb 25E5, cytochrome P-450(25) was detected in both pig kidney and pig liver microsomes. These results indicate a similar or the same species of cytochrome P-450 in pig kidney and liver microsomes catalysing 25-hydroxylation of vitamin D3 and C27 steroids. The N-terminal amino acid sequence of the purified cytochrome P-450(25) from pig kidney microsomes differed from those of hitherto isolated mammalian cytochromes P-450.

  细胞色素P-450酶催化维生素D3的25-羟化（来自猪肾微粒体的细胞色素P-450（25）[Postlind＆Wikvall（1988）Biochem.J.253,549-552]已被进一步纯化。细胞色素P-450的特异含量为15.0 nmol.mg-1蛋白质，并且该蛋白质在二维等电聚焦/SDS/PAGE上显示出一个明显的等电点为7.4，分子量为50,500的单一斑点。对于维生素D3的25-羟化酶活性为124 pmol.min-1.nmol细胞色素P-450-1，对于1α-羟基维生素D3的酶活性为1375 pmol.min-1.nmol-1。该制剂还催化了5β-胆甾烷-3α,7α-二醇的25-羟化，速率为1000 pmol.min-1.nmol细胞色素P-450-1，以及月桂酸的ω-1羟化，速率为200 pmol.min-1.nmol细胞色素P-450-1。制备了一种针对25-羟化细胞色素P-450的单克隆抗体，称为mAb 25E5。将抗体偶联到Sepharose后，抗体能够结合到肾脏以及猪肝微粒体的细胞色素P-450（25），并在重构系统中免疫沉淀维生素D3和5β-胆甾烷-3α,7α-二醇的25-羟化活性。抗体未抑制对月桂酸的羟化活性。通过SDS/PAGE和mAb 25E5的免疫印迹，检测到细胞色素P-450（25）存在于猪肾和猪肝微粒体中。这些结果表明，在猪肾和肝微粒体中存在相似或相同的细胞色素P-450物种，可催化维生素D3和C27类固醇的25-羟化。从猪肾微粒体中纯化的细胞色素P-450（25）的N末端氨基酸序列与迄今为止分离的哺乳动物细胞色素P-450的氨基酸序列不同。
• Expression and Characterization of CYP4V2 as a Fatty Acid ω-Hydroxylase
  作者：Mariko Nakano、Edward J. Kelly、Allan E. Rettie

  DOI：10.1124/dmd.109.028530

  日期：2009.11

  Bietti's crystalline dystrophy is an ocular disease that is strongly associated with polymorphisms in the CYP4V2 gene. CYP4 enzymes are typically microsomal fatty acid ω-hydroxylases that function together with mitochondrial and peroxisomal β-oxidation enzymes to degrade cellular lipids. Indeed, ocular and peripheral cells cultured from patients with Bietti's have been reported to exhibit abnormal lipid metabolism. However, CYP4V2 possesses low sequence homology to other members of the CYP4 family. Therefore, we cloned and expressed CYP4V2 and analyzed the functional characteristics of this new cytochrome P450 enzyme. We find that CYP4V2 is a selective ω-hydroxylase of saturated, medium-chain fatty acids with relatively high catalytic efficiency toward myristic acid. Moreover, N -hydroxy- N ′-(4- n -butyl-2-methylphenyl formamidine) (HET0016) is a nanomolar inhibitor of the enzyme. Therefore, CYP4V2 exhibits catalytic functions typical of a human CYP4 enzyme, but with a distinctive chain-length selectivity coupled with high ω-hydroxylase specificity. Consequently, defective ω-oxidation of ocular fatty acids/lipids secondary to mutations in the CYP4V2 gene appears to be a plausible mechanism underlying Bietti's crystalline dystrophy.

  比蒂晶体营养不良症是一种眼部疾病，与 CYP4V2 基因的多态性密切相关。CYP4 酶是典型的微粒体脂肪酸ω-羟化酶，与线粒体和过氧化物酶β-氧化酶共同作用，降解细胞脂质。事实上，有报道称，从 Bietti's 症患者身上培养出的眼部和外周细胞表现出异常的脂质代谢。然而，CYP4V2 与 CYP4 家族其他成员的序列同源性较低。因此，我们克隆并表达了 CYP4V2，并分析了这种新细胞色素 P450 酶的功能特征。我们发现，CYP4V2 是饱和中链脂肪酸的选择性ω-羟化酶，对肉豆蔻酸的催化效率相对较高。此外，N-羟基-N ′-（4-正丁基-2-甲基苯基甲脒）（HET0016）是该酶的纳摩尔抑制剂。因此，CYP4V2 具有人类 CYP4 酶的典型催化功能，但具有独特的链长选择性和高ω-羟化酶特异性。因此，CYP4V2 基因突变导致的眼脂肪酸/脂质的ω-氧化缺陷似乎是导致比蒂晶体营养不良症的一个合理机制。
• Identification of CYP4A11 as the Major Lauric Acid ω-Hydroxylase in Human Liver Microsomes
  作者：Pnina K. Powell、Imre Wolf、Jerome M. Lasker

  DOI：10.1006/abbi.1996.0501

  日期：1996.11

  the major hepatic laurate omega-hydroxylase in humans. Western blotting with rat CYP4A1 antibodies was used to monitor a cross-reactive P450 protein (M(r) = 52 kDa) during its isolation from human liver microsomes. The purified enzyme (7.4 nmol P450/mg protein) had an NH2-terminal amino acid sequence identical to that predicted from the human CYP4A11 cDNA over the first 20 residues found. Upon reconstitution

  人肝微粒体能够在omega-1和omega-1位置氧化月桂酸（月桂酸酯）（一种模型中链脂肪酸），分别形成12-和11-羟基月桂酸酯。这些月桂酸酯羟基化反应显然是由不同的P450酶催化的。虽然已将负责人类肝脏中微粒体月桂酸酯omega-1羟基化的P450确定为CYP2E1，但催化ω-羟基化的酶的定义仍然不明确。为此，我们采用了常规的纯化和免疫化学技术来表征人体内主要的肝月桂酸酯ω-羟化酶。大鼠CYP4A1抗体的蛋白质印迹用于监测与人肝微粒体分离的交叉反应性P450蛋白（M（r）= 52 kDa）。纯化的酶（7。（4 nmol P450 / mg蛋白）在发现的前20个残基上具有与人CYP4A11 cDNA预测的相同的NH2末端氨基酸序列。用P450还原酶和细胞色素b5重构后，CYP4A11被证明是有效的月桂酸酯ω-羟化酶，其形成的周转率为45.7 nmol形成的12-羟基月桂酸酯/ min /
• Adas F.; Salauen J.P.; Berthou F., J Lipid Res, 1999, 0022-2275, 1990-7
  作者：Adas F.、Salauen J.P.、Berthou F.、Picart D.、Simon B.、Amet Y.

  DOI：——

  日期：——