D-alpha-生育酚醋酸酯 | 52225-20-4

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: D-alpha-生育酚醋酸酯
• 中文别名: D-α-生育酚乙酸酯；维生素E油；(+)-α-生育酚醋酸酯；D-维生素E乙酸酯；D-Alpha-生育酚乙酸酯；D-α-生育酚醋酸酯；D-Α-生育酚乙酸；醋酸生育酚；乙酸维生素E；α-生育酚乙酸酯；alpha-生育酚乙酸酯；维生素E醋酸酯
• 英文名称: RRR-α-tocopheryl acetate
• 英文别名: vitamin E acetate；tocopheryl acetate；α-tocopherol acetate；tocopherol acetate；α-tocopheryl acetate；DL‑α‑tocopheryl acetate；DL-α-tocopherol acetate；D-α-tocopherol acetate；acetate α-tocopherol；alpha-tocopheryl acetate；R,R,R-α-tocopherol acetate；d-alpha-Tocopheryl acetate；Alpha-Tocopherol Acetate；[(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] acetate
• CAS: 52225-20-4；58-95-7
• 化学式: C₃₁H₅₂O₃
• 分子量: 472.752
• InChiKey: ZAKOWWREFLAJOT-CEFNRUSXSA-N

物化性质

• 熔点：
  -27.5°
• 沸点：
  bp0.01 184°; bp0.025 194°; bp0.3 224°
• 密度：
  0.96 g/mL at 20 °C(lit.)
• 闪点：
  9℃
• 溶解度：
  可溶于氯仿、乙醇（少量）、甲醇（少量）
• 物理描述：
  D-alpha-tocopheryl acetate appears as odorless off-white crystals. Darkens at 401° F. (NTP, 1992)
• 保留指数：
  3131;3132

计算性质

• 辛醇/水分配系数(LogP)：
  10.8
• 重原子数：
  34
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

除了任何后续信息外，由于d-α-生育酚醋酸酯与α-生育酚醋酸酯的化学性质密切相关，请参考α-生育酚醋酸酯的药品信息页面以获取更多数据。肝脏的。

_In addition to any following information, owing to d-alpha-Tocopherol acetate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._ Hepatic.

来源:DrugBank

代谢

α-生育酚的主要肝脏代谢始于内质网，通过CYP4F2/CYP3A4依赖的ω-羟基化作用在脂肪族侧链上，形成13'-羟基色醇（13'-OH）代谢物。接下来，过氧化物酶体的ω-氧化作用产生13'-羧基色醇（13'-COOH）。这两个步骤之后是五个连续的β-氧化反应，目的是缩短α-生育酚代谢物侧链。这些β-氧化反应的第一个仍然发生在过氧化物酶体环境中，生成羧基二甲基癸基羟基色醇（CDMDHC，11'-COOH）。然后，在线粒体中，第二个β-氧化步骤形成羧基甲基辛基羟基色醇（CDMOHC，9'-COOH）代谢物。由于CDMDHC和CDMOHC的侧链长度在13到9个碳单位之间，它们被认为是长链代谢物。这些长链代谢物的疏水性意味着它们不会通过尿液排出，但已经在人类微粒体、血清和粪便中找到。接下来的两个β-氧化反应，仍然在线粒体环境中，产生两个中等链长度的代谢物：羧基甲基己基羟基色醇（CDMHHC，7'-COOH），接着是羧基甲基丁基羟基色醇（CMBHC，5'-COOH）。这两个中等链长度的代谢物在人类血浆、粪便和尿液中都有发现。最后，最后的线粒体β-氧化生成了α-生育酚代谢的分解终产物：羧基乙基-羟基色烷（CEHC，3'-COOH），它被认为是一种短链代谢物。CEHC在人类血浆、血清、尿液和粪便中都有观察到。

Primary hepatic metabolism of alpha-tocopherol begins in the endoplasmic reticulum with CYP4F2/CYP3A4 dependent ω-hydroxylation of the aliphatic side-chain, which forms the 13’-hydroxychromanol (13’-OH) metabolite. Next, peroxisome ω-oxidation results in 13’-carboxychromanol (13’-COOH). Following these two steps are five consecutive β-oxidation reactions which serve to shorten the alpha-tocopherol metabolite side-chains. The first of these β-oxidations occurs still in the peroxisome environment, generating carboxydimethyldecylhydroxychromanol (CDMDHC, 11’-COOH). Then, in the mitochondrion, the second β-oxidation step forms the carboxymethyloctylhydroxychromanol (CDMOHC, 9’-COOH) metabolite. Since both CDMDHC and CDMOHC possess a side-chain length of between 13 to 9 carbon units, they are considered long-chain metabolites. The hydrophobicity of these long-chain metabolites means they are not excreted in the urine but have been found in human microsomes, serum, and feces. The next two β-oxidation reactions, still within the mitochondrion environment, produce two intermediate chain metabolites: carboxymethylhexylhydroxychromanol (CDMHHC, 7’-COOH), followed by carboxymethylbutylhydroxychromanol (CMBHC, 5’-COOH). Both of these intermediate chain metabolites are found in human plasma, feces, and urine. Finally, the last mitochrondrion β-oxidation generates the catabolic end product of alpha-tocopherol metabolism: carboxyethyl-hydroxychromans (CEHC, 3'-COOH), which is considered a short-chain metabolite. CEHC has been observed in human plasma, serum, urine, and feces.

来源:DrugBank

毒理性

• 蛋白质结合

除了任何后续信息外，由于d-α-生育酚醋酸与α-生育酚醋酸在化学性质上密切相关，请参考α-生育酚醋酸的药物信息页面以获取更多数据。在血液中与β-脂蛋白结合。

_In addition to any following information, owing to d-alpha-Tocopherol acetate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._ Bound to beta-lipoproteins in blood.

来源:DrugBank

毒理性

• 蛋白质结合

目前无法轻松获取有关α-生育酚与蛋白质结合的数据。实际上，除了肝脏之外的组织中是否存在α-生育酚结合蛋白这一问题正在持续研究中。

Data regarding the protein binding of alpha-tocopherol is not readily accessible at the moment. In fact, the existence of alpha-tocopherol binding proteins in tissues other than the liver is involved in ongoing investigations.

来源:DrugBank

吸收、分配和排泄

• 吸收

除了任何后续信息外，由于d-α-生育酚醋酸酯与α-生育酚醋酸酯的化学性质密切相关，请参考α-生育酚醋酸酯的药品信息页面以获取更多数据。从胃肠道吸收率为50%至80%。

_In addition to any following information, owing to d-alpha-Tocopherol acetate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._ 50 to 80% absorbed from gastrointestinal tract.

来源:DrugBank

吸收、分配和排泄

• 消除途径

除了任何后续信息外，由于d-α-生育酚醋酸酯与α-生育酚醋酸酯的化学性质密切相关，请也参考α-生育酚醋酸酯的药品信息页面以获取更多数据。

_In addition to any following information, owing to d-alpha-Tocopherol acetate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._

来源:DrugBank

吸收、分配和排泄

• 分布容积

除了任何后续信息外，由于d-α-生育酚醋酸酯与α-生育酚醋酸酯的化学性质密切相关，请也参考α-生育酚醋酸酯的药品信息页面以获取更多数据。

_In addition to any following information, owing to d-alpha-Tocopherol acetate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._

来源:DrugBank

吸收、分配和排泄

• 清除

除了任何后续信息外，由于d-α-生育酚醋酸酯与α-生育酚醋酸酯的化学性质密切相关，请也参考α-生育酚醋酸酯的药品信息页面以获取更多数据。

_In addition to any following information, owing to d-alpha-Tocopherol acetate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data._

来源:DrugBank

吸收、分配和排泄

• 吸收

当维生素E被摄入时，肠道的吸收在限制其生物利用度方面起着主要作用。众所周知，维生素E是一种脂溶性维生素，它遵循其他亲脂性分子和脂质的肠道吸收、肝脏代谢和细胞摄取过程。因此，维生素E的肠道吸收需要富含脂质的食物的存在。特别是，稳定的α-生育酚醋酸酯在胰腺中通过胆酸依赖性脂肪酶或通过肠粘膜酯酶进行水解。随后在小肠吸收，通过从乳状脂肪小球转移到由磷脂和胆酸组成的水溶性多和单层囊泡和混合微胶中。由于维生素E进入肠细胞与其他类型的脂质相比效率较低，这可能是维生素E相对生物利用度较低的原因。α-生育酚醋酸酯本身嵌入在其水解和肠细胞摄取明显低于混合微胶的基质中。随后，维生素E从混合微胶进入肠细胞的摄取原则上遵循两种不同的途径：（a）通过被动扩散，和（b）通过受体介导的转运，包括各种细胞转运，如清道夫受体B类1型、尼曼-皮克C1样蛋白、ATP结合盒（ABC）转运体ABCG5/ABCG8或ABCA1等。维生素E从肠腔的吸收依赖于胆汁和胰液分泌、微胶形成、进入肠细胞和乳糜微粒分泌。在任何步骤中的缺陷都可能导致吸收受损。乳糜微粒分泌是维生素E吸收所必需的，是高效吸收的重要因素。所有各种形式的维生素E在肠道吸收和随后的乳糜微粒分泌中表现出相似的外观效率。在乳糜微粒分解过程中，部分维生素E被分配到所有循环脂蛋白中。含有新吸收的维生素E的乳糜微粒残骸随后被肝脏摄取。维生素E以极低密度脂蛋白（VLDLs）的形式从肝脏分泌。血浆维生素E浓度取决于维生素E从肝脏的分泌，只有一种形式的维生素E，即α-生育酚，总是被肝脏优先重新分泌。因此，肝脏负责区分生育酚，并优先使血浆富含α-生育酚。在肝脏中，α-生育酚转移蛋白（alpha-TTP）可能负责区分功能，其中RRR-或d-α-生育酚对alpha-TTP具有最大的亲和力。然而，人们认为实际吸收的维生素E只有很小一部分。在两名患有胃癌和淋巴细胞性白血病的患者中，淋巴管中的分数吸收仅分别为含有α-生育酚和α-生育酚醋酸酯的餐食中标记的21%和29%。此外，在给一组健康男性分别喂食125毫克、250毫克和500毫克三个单独剂量的实验中，观察到的血浆峰浓度（ng/mL）分别为1822 +/- 48.24、1931.00 +/- 92.54和2188 +/- 147.61。

When vitamin E is ingested, intestinal absorption plays a principal role in limiting its bioavailability. It is known that vitamin E is a fat-soluble vitamin that follows the intestinal absorption, hepatic metabolism, and cellular uptake processes of other lipophilic molecules and lipids. The intestinal absorption of vitamin E consequently requires the presence of lipid-rich foods. In particular, stable alpha-tocopherol acetate undergoes hydrolysis by bile acid-dependant lipase in the pancreas or by an intestinal mucosal esterase. Subsequent absorption in the duodenum occurs by way of transfer from emulsion fat globules to water-soluble multi- and unilamellar vesicles and mixed micelles made up of phospholipids and bile acids. As the uptake of vitamin E into enterocytes is less efficient compared to other types of lipids, this could potentially explain the relatively low bioavailability of vitamin E. Alpha-tocopherol acetate itself is embedded in matrices where its hydrolysis and its uptake by intestinal cells are markedly less efficient than in mixed micelles. Subsequently, the intestinal cellular uptake of vitamin E from mixed micelles follows in principle two different pathways across enterocytes: (a) via passive diffusion, and (b) via receptor-mediated transport with various cellular transports like scavenger receptor class B type 1, Niemann-Pick C1-like protein, ATP-binding cassette (ABC) transporters ABCG5/ABCG8, or ABCA1, among others. Vitamin E absorption from the intestinal lumen is dependent upon biliary and pancreatic secretions, micelle formation, uptake into enterocytes, and chylomicron secretion. Defects at any step can lead to impaired absorption.. Chylomicron secretion is required for vitamin E absorption and is a particularly important factor for efficient absorption. All of the various vitamin E forms show similar apparent efficiencies of intestinal absorption and subsequent secretion in chylomicrons. During chylomicron catabolism, some vitamin E is distributed to all the circulating lipoproteins. Chylomicron remnants, containing newly absorbed vitamin E, are then taken up by the liver. Vitamin E is secreted from the liver in very low density lipoproteins (VLDLs). Plasma vitamin E concentrations depend upon the secretion of vitamin E from the liver, and only one form of vitamin E, alpha-tocopherol, is ever preferentially resecreted by the liver. The liver is consequently responsible for discriminating between tocopherols and the preferential plasma enrichment with alpha-tocopherol. In the liver, the alpha-tocopherol transfer protein (alpha-TTP) likely is in charge of the discriminatory function, where RRR- or d-alpha-tocopherol possesses the greatest affinity for alpha-TTP. It is nevertheless believed that only a small amount of administered vitamin E is actually absorbed. In two individuals with gastric carcinoma and lymphatic leukemia, the respective fractional absorption in the lymphatics was only 21 and 29 percent of label from meals containing alpha-tocopherol and alpha-tocopheryl acetate, respectively. Additionally, after feeding three separate single doses of 125 mg, 250 mg, and 500 mg to a group of healthy males, the observed plasma peak concentrations (ng/mL) were 1822 +/- 48.24, 1931.00 +/- 92.54, and 2188 +/- 147.61, respectively.

来源:DrugBank

安全信息

• WGK Germany：
  1
• 海关编码：
  29362800
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

DL-α-生育酚醋酸酯是维生素E的衍生物，常被用于肠内营养中。

体内研究

DL-α-生育酚醋酸酯（α-TA）能增加肝脏、大脑、睾丸和心脏等组织中的胆固醇水平。在调整蛋白质含量后，大脑中的胆固醇水平明显高于其他组织。此外，DL-α-生育酚醋酸酯还能提高小鼠肝、脑和睾丸中脂质过氧化水平。

反应信息

• 作为反应物：
  描述：

  D-alpha-生育酚醋酸酯 在 potassium hydroxide 、 盐酸 作用下， 以 乙醇 、 乙基-异丙基醚 、 水 为溶剂， 反应 1.0h， 生成 天然维生素E
  参考文献：
  名称：

  迈向维生素E的现代定义-醌假说的证据

  摘要：

  我们报告了生育酚醌天然产物α-生育酚醌（ATQ）的合成，生物学和药理活性；α-生育酚的氧化代谢产物。ATQ是一种有效的抗氧化应激的细胞保护剂，其生物活性取决于其经历可逆的两电子氧化还原循环的能力。ATQ具有口服生物利用度，具有良好的药代动力学特征，并已证明对Friedreich共济失调患者具有有益的临床反应。ATQ是维生素E衍生的醌类代谢产物的更广泛成员之一，其全部或部分归因于维生素E的活性。

  DOI：

  10.1016/j.bmcl.2011.10.117
• 作为产物：
  描述：

  天然维生素E 生成 D-alpha-生育酚醋酸酯
  参考文献：
  名称：

  Process for the preparation of tocol acylates and tocopherol acylates

  摘要：

  本发明涉及一种制备生育酚酰化物或生育醇酰化物的方法，其步骤如下：a) 将生育酚或生育醇与酰化剂混合形成反应混合物；b) 用微波能量辐射反应混合物以形成生育酚酰化物或生育醇酰化物；c) 从反应混合物中分离出生育酚酰化物或生育醇酰化物。

  公开号：

  US20020017451A1
• 作为试剂：
  描述：

  三甲基氢醌 、 盐酸 、 异植物醇 在 氯化锌 水 、 甲苯 、 氯化钠 、 magnesium sulfate 、 D-alpha-生育酚醋酸酯 、 乙酸异丁酯 作用下， 以 乙酸异丁酯 为溶剂， 反应 5.0h， 以whereby 67.0 g of the title compound was obtained as a brown oil (yield: 98.6%, GLC purity: 98.6%, α-tocopheryl acetate content: 0.2%, isobutyl acetate recovery rate: 92%)的产率得到天然维生素E
  参考文献：
  名称：

  Process for the preparation of .alpha.-tocopherol

  摘要：

  提供一种制备α-生育酚的方法。根据该方法，在以下任一溶剂的存在下，对三甲基羟基苯醌和特定的叶绿素衍生物或异叶绿素进行缩合反应：（i）碳酸酯；（ii）由以下公式表示的低级脂肪酸酯：R.sup.1 COOR.sup.2，其中R.sup.1表示具有1-4个碳原子的低级烷基基团，R.sup.2表示具有1-5个碳原子的低级烷基基团，但乙酸甲酯和乙酸乙酯除外；（iii）非极性溶剂和具有1-5个碳原子的低级醇的混合溶剂；和（iv）非极性溶剂和低级脂肪酸酯的混合溶剂。

  公开号：

  US06020505A1

文献信息

• [EN] PHENOTHIAZINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHÉNOTHIAZINE ET LEURS UTILISATIONS
  申请人：CAMP4 THERAPEUTICS CORP

  公开号：WO2019195789A1

  公开（公告）日：2019-10-10

  The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA).

  本发明提供了吩噻嗪化合物，其制备方法，包含该化合物的药物组合物，以及在治疗各种疾病或症状中使用该化合物或组合物，例如核糖体紊乱和核糖体病，例如钻石-布莱克范贫血（DBA）。
• Flavonoid derivative
  申请人：Buchholz Herwig

  公开号：US20070134172A1

  公开（公告）日：2007-06-14

  The invention relates to a novel flavonoid derivative, to an extract comprising the flavonoid derivative, to the cosmetic and pharmaceutical use thereof, to preparations comprising the flavonoid derivative or extract, and to a process for the preparation of the flavonoid derivative or extract.

  这项发明涉及一种新型黄酮衍生物，一种包含该黄酮衍生物的提取物，以及其在化妆品和药用方面的使用，包括含有该黄酮衍生物或提取物的制剂，以及一种制备该黄酮衍生物或提取物的方法。
• 4-Imidazol-1-yl-butane-1-sulfonic acid ionic liquid: Synthesis, structural analysis, physical properties and catalytic application as dual solvent-catalyst
  作者：Nader Ghaffari Khaligh、Taraneh Mihankhah、Mohd Rafie Johan、Joon Ching Juan

  DOI：10.1080/10426507.2018.1487426

  日期：2019.9.2

  Abstract 4-Imidazol-1-yl-butane-1-sulfonic acid (ImBu-SO3H) has been successfully synthetized and fully characterized by FT-IR and high-resolution NMR spectroscopy (1H, 13C). The “plausible” alternative structures of ImBu-SO3H were discussed on the basis of its NMR data. The ionic liquid showed interesting dual solvent-catalyst property, which was studied experimentally for the acetylation of a variety

  摘要 4-Imidazol-1-yl-butane-1-sulfonic acid (ImBu-SO3H) 已成功合成并通过 FT-IR 和高分辨率 NMR 光谱 (1H, 13C) 进行了充分表征。ImBu-SO3H 的“合理”替代结构在其 NMR 数据的基础上进行了讨论。离子液体显示出有趣的双溶剂-催化剂性质，实验研究了其乙酰化各种官能化的醇、酚、硫醇、胺和 α-生育酚 (α-CTP) 作为维生素 E 的最活性形式与乙酸酐并且在很短的反应时间内提供了良好的收率。ImBu-SO3H 通过产品萃取成功回收，随后 5 次运行的平均回收率为 82%。即使在连续五次运行后，回收的 ImBu-SO3H 的催化活性也几乎没有损失。图形概要
• [EN] HSD17B13 INHIBITORS AND USES THEREOF<br/>[FR] COMPOSÉS ET UTILISATIONS DE CEUX-CI
  申请人：INIPHARM INC

  公开号：WO2021211974A1

  公开（公告）日：2021-10-21

  Described herein are HSD17B13 inhibitors and pharmaceutical compositions comprising said inhibitors. The subject compounds and compositions are useful for the treatment of liver disease, metabolic disease, or cardiovascular disease, such as NAFLD or NASH, or drug induced liver injury (DILI).

  本发明涉及HSD17B13抑制剂及包含所述抑制剂的药物组合物。所述化合物和组合物可用于治疗肝病、代谢性疾病或心血管疾病，例如非酒精性脂肪肝病（NAFLD）或非酒精性脂肪肝炎（NASH），或药物诱导的肝损伤（DILI）。
• Rheology modifier/hair styling resin
  申请人：Drzewinski Michael

  公开号：US20060084586A1

  公开（公告）日：2006-04-20

  A rheology modifier/hair styling resin which is a crosslinked, linear poly(vinyl amide/polymerizable carboxylic acid) copolymer exhibits advantageous hair care properties of high viscosity and long-lasting curl retention.

  一种流变改性剂/头发造型树脂，它是一种交联的、线性的聚（乙烯酰胺/可聚合的羧酸）共聚物，展现出高粘度和持久卷曲保持性的优良护发特性。

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