Γ-十八碳三烯酸 | 463-40-1

• 物质功能分类: 食品添加剂 - 营养强化剂 - 脂肪酸类
• 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: Γ-十八碳三烯酸
• 中文别名: alpha-亚麻酸；α-亚麻酸；亚麻酸；9,12,15-十八碳三烯酸；a-亚麻酸；亚麻油酸；亚麻子油酸；全顺式-9,12,15-十八碳三烯酸；顺-9,12,15-十八碳三烯酸
• 英文名称: (9Z,12Z,15Z)-octadeca-9-12,15-trienoic acid
• 英文别名: linolenic Acid；α-linolenic acid；alpha-linolenic acid；(Z,Z,Z)-9,12,15-octadecatrienoic acid；ALA；9,12,15-octadecatrienoic acid；9,12,15-octadecatrienoic acid, (Z,Z,Z)-；(Z,Z,Z)-octadeca-9,12,15-trienoic acid；9Z,12Z,15Z-octadecatrienoic acid；γ-linolenic acid；octadecatrienoic acid；9Z,12Z,15Z-α-linolenic acid；α-LA；(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid
• CAS: 463-40-1；68424-45-3
• 化学式: C₁₈H₃₀O₂
• 分子量: 278.435
• InChiKey: DTOSIQBPPRVQHS-PDBXOOCHSA-N

物化性质

• 熔点：
  -11 °C(lit.)
• 沸点：
  230-232 °C1 mm Hg(lit.)
• 密度：
  0.914 g/mL at 25 °C(lit.)
• 闪点：
  >230 °F
• 溶解度：
  可溶于氯仿、乙酸乙酯（少许）、甲醇（少许）
• LogP：
  6.52
• 物理描述：
  Linolenic acid is a clear colorless liquid. (NTP, 1992)
• 蒸汽压力：
  0.05 mm Hg at 257 °F (NTP, 1992)
• 碰撞截面：
  170.7 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]
• 保留指数：
  2122;2102;2120;2113;2115

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  20
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

毒理性

• 毒性总结

α-亚麻酸或ALA被认为是一种必需脂肪酸，因为它对人类健康至关重要，但人类自身无法合成。它实际上是一种植物来源的脂肪酸。人类可以从ALA合成其他欧米茄-3脂肪酸，包括二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）。EPA是3系列前列腺素的先驱，5系列白三烯和3系列血栓素的前体。这些二十烷酸具有抗炎和抗动脉粥样硬化的特性。ALA的代谢物也可能抑制促炎二十烷酸前列腺素E2（PGE2）和白三烯B4（LTB4）以及促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的产生。欧米茄-3脂肪酸如ALA及其副产品可以调节许多基因的表达，包括那些与脂肪酸代谢和炎症有关的基因。它们通过影响转录因子的活性来调节基因表达，包括NF-κB和过氧化物酶体增殖物激活受体（PPAR）家族成员。ALA及其代谢物整合到细胞膜中可以影响膜流动性，可能在抗炎活性、抑制血小板聚集以及ALA的抗增殖作用中发挥作用。ALA首先通过delta6去饱和酶代谢为硬脂酸。

Alpha Linolenic Acid or ALA is considered an essential fatty acid because it is required for human health, but cannot be synthesized by humans. It is in fact a plant-derived fatty acid. Humans can synthesize other omega-3 fatty acids from ALA, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA is a precursor of the series-3 prostaglandins, the series-5 leukotrienes and the series-3 thromboxanes. These eicosanoids have anti-inflammatory and anti-atherogenic properties. ALA metabolites may also inhibit the production of the pro-inflammatory eicosanoids, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), as well as the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Omega-3 fatty acids like ALA and its byproducts can modulate the expression of a number of genes, including those involved with fatty acid metabolism and inflammation. They regulate gene expression through their effects on the activity of transcription factors including NF-kappa B and members of the peroxisome proliferator-activated receptor (PPAR) family. Incorporation of ALA and its metabolites in cell membranes can affect membrane fluidity and may play a role in anti-inflammatory activity, inhibition of platelet aggregation and possibly in anti-proliferative actions of ALA. ALA is first metabolized by delta6 desaturease into steridonic acid.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

未列入国际癌症研究机构(IARC)的清单。

Not listed by IARC.

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  1
• 海关编码：
  2916190090
• 危险品运输编号：
  UN1170 - class 3 - PG 2 - Ethanol
• 危险标志：
  GHS02,GHS07
• 危险性描述：
  H225,H319
• 危险性防范说明：
  P210,P305 + P351 + P338,P370 + P378,P403 + P235

制备方法与用途

这段文字详细介绍了γ-亚麻酸的生产方法。主要提到了四种不同的生产方法：

1. 月见草油法：首先将月见草油皂化、提取脂肪酸，然后通过尿素包合法富集γ-亚麻酸。

2. 月见草种子榨油法：从月见草种子中分离油脂，进行分馏制得γ-亚麻酸。这种方法较为传统。

3. 微生物发酵法：利用丝状菌毛霉、深黄被孢霉等微生物发酵后提取干燥菌丝体中的脂肪酸，再精制得到γ-亚麻酸。这种方法具有较高的效率，但需要控制生产环境以防止其氧化。

4. 尿素包合法：此方法适用于多烯不饱和脂肪酸的富集，并可用于α-亚麻酸乙酯、γ-亚麻酸等化合物的制备。

每种方法都有其特点和适用范围。在实际生产中，可以根据具体情况选择合适的生产工艺。为了确保产品质量和稳定性，在生产过程中应注意防止氧化等问题。

反应信息

• 作为反应物：
  描述：

  Γ-十八碳三烯酸 在 cyclopentadienylruthenium(II) trisacetonitrile hexafluorophosphate 、 重水 作用下， 以 氘代丙酮 为溶剂， 反应 24.0h， 生成 11,11,14,14,D4-linolenic acid
  参考文献：
  名称：

  特定位置的氘代多不饱和烯烃的氘代

  摘要：

  药物和生物学相关分子的选择性氘化在制药行业中变得越来越重要。多不饱和脂肪酸（PUFA）在其双烯丙基位点的位点选择性同位素增强已被认为是防止这些分子氧化损伤的一种独特方法，这种氧化损伤与神经元和视网膜疾病，动脉粥样硬化和衰老有关。用于制备位点选择性氘代PUFA的典型方法需要相当长，费力且昂贵的合成。在这份报告中，我们公开了非常有效的催化方案，用于在特殊动力学控制下对PUFA和类似聚烯烃进行位点特异性氘化。氧化氘（D 2O）不仅被认为是氘源，而且在整个反应机制中也起着至关重要的作用，该机制负责避免形成热力学上有利的副产物。

  DOI：

  10.1021/acs.joc.7b02169
• 作为产物：
  描述：

  亚麻酸乙酯 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 Γ-十八碳三烯酸
  参考文献：
  名称：

  Linolenic acid-modified PEG-PCL micelles for curcumin delivery

  摘要：

  In this study, a novel linolenic acid-modified poly(ethylene glycol)-b-poly(epsilon-caprolactone) copolymer was prepared through radical addition, ring-opening polymerization, and N-acylation reactions. Its structure was characterized by H-1 NMR and GPC. Micelles were developed by thin-film hydration and used as a delivery system for curcumin with high drug loading capacity of 12.80% and entrapment efficiency of 98.53%. The water solubility of curcumin was increased to 2.05 mg/mL, which was approximately 1.87 x 10(5) times higher than that of free curcumin. The micelles were spherical shape with an average diameter of 20.8 +/- 0.8 nm. X-ray diffraction and FT-IR studies suggested that curcumin existed in the polymeric matrices under pi-pi conjugation and hydrogen bond interaction with the copolymer. In vitro drug release studies indicated that the curcumin release from linolenic acid-modified copolymer micelles met controlled release, and its release rate was less than that from the linolenic acid-unmodified copolymer micelles. Cytotoxicities against Hela and A-549cells demonstrated that the additional pi-pi conjugation could affect curcumin's anticancer activity through reducing its release from micelles. Hemolysis test and intravenous irritation test results revealed that the linolenic acid-modified copolymer was safe for intravenous injection. The plasma AUC(0-infinity) and MRT0-infinity of curcumin-loaded linolenic acid-conjugated poly(ethylene glycol)-b-poly(epsilon-caprolactone) copolymer micelles were 2.75- and 3.49-fold higher than that of control solution, respectively. The CLz was also decreased by 2.75-fold. So, this linolenic acid-modified copolymer might be a carrier candidate for curcumin delivery. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ijpharm.2014.05.059
• 作为试剂：
  描述：

  维A酸 在 Γ-十八碳三烯酸 、 二乙烯三胺五醋酸 、 lipoxygenase-2 、 Na phosphate buffer 作用下， 生成 all-trans-5,6-Epoxyretinoic acid
  参考文献：
  名称：

  大豆脂氧合酶-2和-3的全反式视黄酸的5,6-Epoxidation。

  摘要：

  以全反式视黄酸为共底物，研究了高纯度大豆脂氧合酶-2和-3的共氧化活性。在亚油酸的存在下，两种同工酶都能迅速降解维甲酸，但脂氧合酶2的共氧化活性比脂氧合酶3的高。在共氧化过程中，形成了5，6-环氧维甲酸作为主要产物。手性相（Ceramospher Chiral RU-1）上的HPLC发现环氧化合物的外消旋混合物，表明它是由过氧自由基的氧化攻击形成的。

  DOI：

  10.1271/bbb.58.140

文献信息

• SUBSTITUTED ARYL AND HETEROARYL CARBOXYLIC ACID HYDRAZIDES OR SALTS THEREOF AND USE THEREOF TO INCREASE STRESS TOLERANCE IN PLANTS
  申请人：BAYER CROPSCIENCE AKTIENGESELLSCHAFT

  公开号：US20180206495A1

  公开（公告）日：2018-07-26

  Substituted aryl- and heteroarylcarbonyl hydrazides The invention relates to substituted aryl- and heteroarylcarbonyl hydrazides of the general formula (I) or salts thereof where the radicals of the formula (I) are each as defined in the description for enhancing stress tolerance in plants to abiotic stress, and for enhancing plant growth and/or for increasing plant yield.

  该发明涉及通式（I）的取代芳基和杂芳基羰基肼或其盐，其中通式（I）的基团如描述中所定义，用于增强植物对非生物胁迫的耐受性，促进植物生长和/或增加植物产量。
• HERBICIDAL AND FUNGICIDAL 5-OXY-SUBSTITUTED 3-PHENYLISOXAZOLINE-5-CARBOXAMIDES AND 5-OXY-SUBSTITUTED 3-PHENYLISOXAZOLINE-5-THIOAMIDES
  申请人：BAYER CROPSCIENCE AG

  公开号：US20150245616A1

  公开（公告）日：2015-09-03

  Herbicidally and fungicidally active 5-oxy-substituted 3-phenylisoxazoline-5-carboxamides and 5-oxy-substituted 3-phenylisoxazoline-5-thioamides of the formula (I) are described. In this formula (I), X, X 2 to X 6 , R 1 to R 4 are radicals such as hydrogen, halogen and organic radicals such as substituted alkyl. A is a bond or a divalent unit. Y is a chalcogen.

  具有除草和杀菌活性的5-氧代取代的3-苯基异噁唑啉-5-羧酰胺和5-氧代取代的3-苯基异噁唑啉-5-硫酰胺的化合物如下式（I）所述。 在这个式子（I）中，X，X2至X6，R1至R4是氢、卤素和有机基团，如取代烷基等。A是一个键或二价基团。Y是硫族元素。
• THIOL-ENE CLICK CHEMISTRY FOR DRUG CONJUGATES
  申请人：SYSCHEM, INC.

  公开号：US20130323169A1

  公开（公告）日：2013-12-05

  The present invention relates to linker molecules that readily conjugate cellular recognition ligand at one end and drug payload at the other, and are useful in treating or preventing cancer, an autoimmune disease, an inflammatory condition, a central nervous system disorder or an infection. The linker inker molecules of the invention are represented by Formula I, II and III; Linker-Drug compounds represented by Formula IV, V and VI; and Ligand-Linker-Drug conjugates represented by Formula VII, VIII and IX:

  本发明涉及易于在一端结合细胞识别配体和在另一端结合药物载荷的连接分子，并且在治疗或预防癌症、自身免疫疾病、炎症症状、中枢神经系统紊乱或感染方面具有用处。该发明的连接分子由公式I、II和III表示；由公式IV、V和VI表示的连接-药物化合物；以及由公式VII、VIII和IX表示的配体-连接-药物共轭物。
• [EN] QUINOLINE AND QUINAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS QUINOLÉINE ET QUINAZOLINE
  申请人：ACERTA PHARMA BV

  公开号：WO2016055982A1

  公开（公告）日：2016-04-14

  In some embodiments, the invention relates to quinazoline and quinoline compounds of Formula I: (I) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to quinazoline and quinoline compounds, pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of Bruton's tyrosine kinase (BTK) mediated disorders.

  在某些实施例中，该发明涉及式I的喹唑啉和喹啉化合物：(I)或其药用可接受盐，或者涉及包含这些化合物的药物组合物以及它们在治疗中的应用。具体而言，在某些实施例中，本发明涉及喹唑啉和喹啉化合物、其药物组合物以及这些化合物和药物组合物在治疗布鲁顿氨基酸激酶（BTK）介导的疾病中的应用。
• Bna Conjugates and Methods of Use
  申请人：James Kenneth D.

  公开号：US20080207505A1

  公开（公告）日：2008-08-28

  Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, decreasing arterial blood pressure and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, enteral, subcutaneous, pulmonary, and intravenous forms of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the hBNP compound are also disclosed, having an amino acid sequence that is other than the native sequence.

  本发明公开了改性利钠肽化合物及其共轭物。具体而言，提供了至少连接有一个修饰基团的hBNP的共轭形式。这些改性利钠肽化合物共轭物保留了刺激cGMP产生、结合NPR-A受体、降低动脉血压以及在某些实施例中相对于未经改性的对应利钠肽化合物具有改善的循环半衰期的活性。这些化合物和共轭物的口服、静脉注射、肠内、皮下、肺部和静脉形式可作为治疗和/或治疗心脏病症，特别是充血性心力衰竭的治疗。还公开了包含具有各种长度和构型的寡聚结构的修饰基团。此外，还公开了hBNP化合物的类似物，其氨基酸序列与天然序列不同。

表征谱图