2-(3,4-二羟基苯基)乙基丁酸酯 | 644985-85-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 2-(3,4-二羟基苯基)乙基丁酸酯
• 英文名称: hydroxytyrosol butyrate
• 英文别名: hydroxytyrosyl butyrate；2-(3,4-Dihydroxyphenyl)ethyl butanoate
• CAS: 644985-85-3
• 化学式: C₁₂H₁₆O₄
• 分子量: 224.257
• InChiKey: FWSMIAYDVSAALB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-二羟基苯乙酸 在 硫酸 、 erbium(III) triflate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 23.0h， 生成 2-(3,4-二羟基苯基)乙基丁酸酯
  参考文献：
  名称：

  Lipophilic Hydroxytyrosol Esters: Fatty Acid Conjugates for Potential Topical Administration

  摘要：

  Hydroxytyrosol is a potent antioxidant natural molecule isolated from olive leaves and fruits. The presence of three hydroxy groups in its structure poses a limit for the topical application of this lead compound. A set of hydroxytyrosol conjugates with fatty acids at different molecular weights were synthesized under mild conditions. The topical delivery features of this new set of antioxidant molecules were evaluated as a function of their permeation profiles through the human stratum corneum and viable epidermis membranes. A dependence on their partition coefficients, their molecular weights, and their isometric configurations was then postulated. Encouraging results prompt further investigations on the polyfunctional role that hydroxytyrosol conjugates could have as agents in both anti-inflammatory and antioxidant therapies.

  DOI：

  10.1021/np200405s

文献信息

• Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
  作者：Efres Belmonte-Reche、Marta Martínez-García、Pablo Peñalver、Verónica Gómez-Pérez、Ricardo Lucas、Francisco Gamarro、José María Pérez-Victoria、Juan Carlos Morales

  DOI：10.1016/j.ejmech.2016.04.047

  日期：2016.8

  Existing treatments have considerable side effects and increase resistance of the parasites. We have measured antitrypanosomal and antileishmanial activity of natural phenols, tyrosol (TYR) and hydroxytyrosol (HT) and several of their esters and metabolites. We found significant IC50 values against Trypanosoma brucei for HT decanoate ester and HT dodecanoate ester (0.6 and 0.36 μM, respectively). This represents

  锥虫病和利什曼病一直是非洲国家健康和发展的真正挑战。现有疗法具有相当大的副作用并增加了寄生虫的抵抗力。我们已经测量了天然酚，酪醇（TYR）和羟基酪醇（HT）以及它们的一些酯和代谢物的抗胰锥虫和抗疟疾活性。我们发现针对布鲁氏锥虫的有效IC 50值用于HT癸酸酯和HT十二酸酯（分别为0.6和0.36μM）。这表示相对于HT的活性大大增加（分别为79和132倍）。此外，两种化合物均对非肿瘤性人类细胞系MRC-5（分别为118和106）表现出高选择性。然后，我们合成了一个有针对性的化合物库，以探索结构活性。我们发现HT癸酸酯和HT十二酸酯的醚和硫脲类似物在低微摩尔范围内也显示出针对布鲁氏杆菌的IC 50值。总之，二邻苯酚环和中等大小的烷基链对于活性至关重要，而它们之间化学键的性质似乎不太重要。
• Chemoenzymatic synthesis of hydroxytyrosol monoesters and their suppression effect on nitric oxide production stimulated by lipopolysaccharides
  作者：Ayaka Sakakura、Martin Pauze、Atsuhiro Namiki、Megumi Funakoshi-Tago、Hiroomi Tamura、Kengo Hanaya、Shuhei Higashibayashi、Takeshi Sugai

  DOI：10.1080/09168451.2018.1530970

  日期：2019.2.1

  over phenolic hydroxy group in tyrosol, and 2-iodoxybenzoic acid (IBX)-mediated hydroxylation adjacent to the remaining free phenolic hydroxy group. Examination of their suppression effects on nitric oxide production stimulated by lipopolysaccharides in RAW264.7 cells showed that hydroxytyrosol butyrate exhibited the highest inhibition (IC50 7.0 μM) among the tested compounds.

  羟基酪醇[2-（3,4-二羟基苯基）乙醇]的脂肪酸单酯是由酪醇（4-羟基苯基乙醇）分两步通过连续念珠菌南极脂肪酶B催化酚基羟基上的伯脂族羟基的化学选择性酰化反应而合成的。酪醇和2-碘氧基苯甲酸（IBX）介导的羟基化反应，与剩余的游离酚羟基相邻。检查其对RAW264.7细胞中脂多糖刺激的一氧化氮产生的抑制作用，结果表明丁酸羟基酪醇显示出最高的抑制作用（IC50 7.0μM）。
• The potential of hydroxytyrosol fatty acid esters to enhance oral bioavailabilities of hydroxytyrosol and fatty acids: Continuous and slow-release ability in small intestine and blood
  作者：Xinmiao Wang、Qian Wang、Jinghan Yu、Xu Guo、Peiyong Tong、Fawen Yin、Xiaoyang Liu、Dayong Zhou

  DOI：10.1016/j.foodchem.2023.136246

  日期：2023.10

  models indicated that hydroxytyrosol fatty acid esters (HTy-Es) could be hydrolyzed by pancreatic lipase to slow-release of free fatty acids (FAs) and HTy. Meanwhile, the HTy-Es, the liberated FAs and the HTy could cross the membrane and were transported into blood circulation. HTy-Es were further hydrolyzed by carboxylesterase in in vitro rat plasma hydrolysis model, which also showed slow-release of

  大鼠外翻肠囊的 HPLC-UV 分析和体外模拟消化模型表明，羟基酪醇脂肪酸酯 (HTy-Es) 可被胰脂肪酶水解，从而缓慢释放游离脂肪酸 (FAs) 和 HTy。同时，HTy-Es、游离的 FAs 和 HTy 可以穿过细胞膜进入血液循环。HTy-Es 在体外被羧酸酯酶进一步水解大鼠血浆水解模型，也显示 FAs (C1-C4) 和 HTy 的缓慢释放。特别是，随着烷基链长度的增加，水解和转运速率先升高后降低。此外，直链HTy-Es的上述速率大于其支链异构体的速率。因此，上述 FAs 和 HTy 在小肠和血液中的持续和缓慢释放清楚地表明 HTy-Es 将是提高游离脂肪酸和羟基酪醇口服生物利用度的有效方法。
• Synthesis of Bioactive Hydroxytyrosol Esters via Multienzyme Cascade on Electroactive Melanin Lignin Nanoparticles: A One‐Pot Approach without Extra Reducing Agents
  作者：Davide Piccinino、Valentina Ubertini、Eliana Capecchi、Elisabetta Tomaino、Valeria Gigli、Raffaele Saladino

  DOI：10.1002/cctc.202300533

  日期：2023.7.21

  A one‐pot strategy for the synthesis of bioactive hydroxytyrosol esters from tyrosol and lipophilic carboxylic acids has been developedviamultienzyme cascade immobilized on electroactive melanin lignin nanoparticles. The novel catalyst involved the co‐immobilization of lipase and tyrosinase on the polyphenolic support and was operative in the presence of sustainable 2‐methyltetrahydrofuran as organic reaction solvent. The system did not require the use of extra reducing agents for the selective synthesis of catechols. Optoelectronic and electrochemical studies suggested the role played by melanin lignin nanoparticles in the regeneration of the active site of tyrosinase from unproductivemet‐form to reversibledeoxy/oxy‐form. This effect improved the overall activity of tyrosinase in the multienzyme cascade favouring the reduction of undesired quinones to corresponding catechols.

  摘要 开发了一种以酪醇和亲脂性羧酸为原料合成生物活性羟基酪醇酯的单锅策略，该策略是将多酶级联固定在具有电活性的黑色素木质素纳米颗粒上。这种新型催化剂将脂肪酶和酪氨酸酶共同固定在多酚载体上，并可在可持续的 2-甲基四氢呋喃作为有机反应溶剂的情况下工作。该系统在选择性合成儿茶酚时无需使用额外的还原剂。光电和电化学研究表明，黑色素木质素纳米颗粒在将酪氨酸酶的活性位点从非生产性的金属形式再生为可逆的乙氧基/氧形式方面发挥了作用。这种作用提高了酪氨酸酶在多酶级联中的整体活性，有利于将不需要的醌还原为相应的儿茶酚。
• Hydroxytyrosol lipophilic analogues: Enzymatic synthesis, radical scavenging activity and DNA oxidative damage protection
  作者：Salvatore Grasso、Laura Siracusa、Carmela Spatafora、Marcella Renis、Corrado Tringali

  DOI：10.1016/j.bioorg.2006.09.003

  日期：2007.4

  The olive oil phenol hydroxytyrosol (3), as well its metabolite homovanillic alcohol (4), were subjected to chemoselective lipase-catalysed acylations, affording with good yield 10 derivatives (5-14) bearing C-2, C-3, C-4, C-10 and C-18 acyl chains at C-1. Hydroxytyrosol (3) and its lipophilic derivatives showed very good DPPH radical scavenging activity. Compounds 3, 4 and their lipophilic analogues 5-14 were subjected to the atypical Comet test on whole blood cells: 3 and its analogues 5 and 6, with little hydrophobic character (logP <= 1.20), showed a good protective effect against H2O2 induced oxidative DNA damage. The homovanillic alcohol 4 and its analogues 10-14 resulted scarcely effective both as radical scavengers and antioxidant agents. (c) 2006 Elsevier Inc. All rights reserved.