caffeic acid benzyl ester

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: caffeic acid benzyl ester
• 英文别名: benzyl caffeate；Benzyl (E)-3-(3,4-dihydroxyphenyl)acrylate；benzyl 3-(3,4-dihydroxyphenyl)prop-2-enoate
• 化学式: C₁₆H₁₄O₄
• 分子量: 270.285
• InChiKey: WWVKQTNONPWVEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  caffeic acid benzyl ester 在 manganese triacetate 作用下， 以 氯仿 为溶剂， 反应 3.0h， 生成 dibenzyl 6,9,10-trihydroxybenzo[k,l]xanthene-1,2-dicarboxylate
  参考文献：
  名称：

  苯并[k，l] x吨木脂素的合成，DNA / RNA相互作用和生物活性。

  摘要：

  通过一套分光光度法评估了两种新合成的和六种先前报道的苯并氧杂蒽木脂素（BXL）（稀有天然产物的类似物）与DNA / RNA，G-四链体和HSA的相互作用。苯并氧杂蒽核心上是否存在甲氧基和羟基，以及C-1 / C-2侧挂基上的微小修饰-苯环是否存在以及苯环上是否存在甲氧基和羟基-影响了荧光变化，对双链（ds-）和G-四链体结构的结合强度。通常，不具有苯环的化合物在结合时比苯基取代的BXL表现出更强的荧光变化。另一方面，具有未取代的苯环的BXL表现出G-四链体的最佳稳定效果。圆二色光谱结果表明，与ds-DNA / RNA的混合结合方式，凹槽结合和部分嵌入，以及最终堆叠至顶部或底部G-四联体，是BXL与这些靶标的主要结合方式。所有化合物均表现出对HSA的微摩尔结合亲和力和增加的蛋白质热稳定性。对于在苯并氧杂蒽核的C-6，C-9和C-10位置带有羟基的所有BXL，均观察到了中等至强的抗自由基清除活

  DOI：

  10.1016/j.bioorg.2020.104190
• 作为产物：
  描述：

  咖啡酸 在 氯化亚砜 、 盐酸胍 、 三乙胺 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 caffeic acid benzyl ester
  参考文献：
  名称：

  Antiproliferative, antiandrogenic and cytotoxic effects of novel caffeic acid derivatives in LNCaP human androgen-dependent prostate cancer cells

  摘要：

  Caffeic acid and its naturally occurring derivative caffeic acid phenethyl ester (CAPE) have antiproliferative and cytotoxic properties in a variety of cancer cell lines without displaying significant toxicity toward healthy cells, and are considered to be potential anticancer agents. However, little is known about their effects on prostate cancer cells. We synthesized and evaluated the effects of caffeic acid, CAPE (2) and 18 synthetic derivatives on cell viability and androgen-dependent cell proliferation, subcellular localisation and expression of androgen receptor (AR) and secretion of prostate-specific antigen (PSA) in LNCaP human hormone-dependent prostate cancer cells. Several synthetic derivatives of CAPE were strong, concentration-dependent cytotoxic agents in LNCaP cells with IC50 values in the 6.8-26.6 mu M range, potencies that were up to five-fold greater than that of CAPE (33.7 +/- 4.0 mu M). A number of caffeic acid derivatives were inhibitors of androgen-stimulated LNCaP cell proliferation with concomitant inhibition of DHT-stimulated PSA secretion. Compound 24 was the most cytotoxic and antiproliferative caffeic acid derivative (IC50 values of 6.8 +/- 0.3 and 2.4 +/- 0.8 mu M, respectively) inhibiting DHT-stimulated cell proliferation and PSA secretion statistically significantly at concentrations as low as 0.3 mu M. Exposure to DHT increased cytoplasmic and nuclear AR levels and co-treatment with increasing concentrations of compound 24 or CAPE (2), notably, further increased these levels. In conclusion, a number of synthetic derivatives of caffeic acid are potent inhibitors of androgen-dependent prostate cancer cell proliferation and viability, acting, at least in part, via an antiandrogenic mechanism that involves increased nuclear accumulation of (presumably inactive) AR. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.057

文献信息

• Synthesis of Caffeic Acid Phenethyl Ester Derivatives, and Their Cytoprotective and Neuritogenic Activities in PC12 Cells
  作者：Haiming Shi、Dongsheng Xie、Ruoling Yang、Yaqian Cheng

  DOI：10.1021/jf500464k

  日期：2014.6.4

  Twenty-one caffeic acid phenethyl ester (CAPE) derivatives were synthesized, and characterized by IR, HR-MS, 1H and 13C NMR analyses. All compounds were evaluated for their cytoprotective effects against H2O2-induced cytotoxicity and neuritogenic activities in the neurite outgrowth in PC12 cells. Compounds 1 and 20 exhibited stronger cytoprotective activities than their parent compound CAPE at 4 nM. Compounds

  合成了二十一种咖啡酸苯乙酯（CAPE）衍生物，并通过IR，HR-MS，1 H和13 C NMR分析对其进行了表征。评价了所有化合物对PC 12细胞中神经突生长中H 2 O 2诱导的细胞毒性和神经生成活性的细胞保护作用。化合物1和20在4 nM时比其母体化合物CAPE表现出更强的细胞保护活性。化合物1，4，12和13显示出潜在neuritogenic活动在为0.5nM，而化合物19和20在10 nM时引起神经突生长。这项研究的结果表明，CAPE及其衍生物可能是预防神经退行性疾病的潜在功能性食品成分。
• Caffeic Acid Esters Are Effective Bactericidal Compounds Against Paenibacillus larvae by Altering Intracellular Oxidant and Antioxidant Levels
  作者：William Collins、Noah Lowen、David J. Blake

  DOI：10.3390/biom9080312

  日期：——

  activity against PL to determine the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). Caffeic acid isopropenyl ester (CAIE), caffeic acid benzyl ester (CABE), and caffeic acid phenethyl ester (CAPE) were the most effective in inhibiting PL growth and killing PL cell with MICs and MBCs of 125 µg/mL when used individually, and a MIC and MBC of 31.25 µg/mL for each compound

  American Foulbrood（AFB）是一种致命的细菌性疾病，会影响and和幼虫蜜蜂。AFB是由形成内生孢子的幼虫Paenibacillus幼虫（PL）引起的。蜂胶含有多种有机化合物，是蜜蜂觅食的产物，是一种主要来自树木中植物性植物的树脂物质。蜂胶中常见的几种咖啡酸酯类化合物已显示出对PL的抗菌活性。在这项研究中，合成，纯化，光谱分析六种不同的咖啡酸酯，并测试它们对PL的活性，以确定最小抑菌浓度（MIC）和最小杀菌浓度（MBC）。咖啡酸异丙烯基酯（CAIE），咖啡酸苄基酯（CABE），单独使用的MIC和MBC为125 µg / mL，而咖啡酸苯乙酯（CAPE）则最能有效抑制PL生长并杀死PL细胞，当使用CAIE时，每种化合物的MIC和MBC分别为31.25 µg / mL CABE和CAPE结合使用可防止PL。这些化合物通过杀菌作用抑制细菌的生长，这种作用显示出细胞被杀死，但在18
• Inhibitory Effects of Caffeic Acid Ester Analogues on Free Radicals and Human Liver Microsome CYP1A2 Activities
  作者：Churdsak Jaikang、Chaiyavat Chaiyasut、Paitoon Narongchai、Kanokporn Niwatananun、Siripun Narongchai、Winthana Kusirisin

  DOI：10.2174/157340611794859316

  日期：2011.3.1

  Ethyl caffeate (EC), octyl caffeate(OC), benzyl caffeate(BC) and phenethyl caffeate(PC) were synthesized and evaluated for scavenging of superoxide anion, nitric oxide radical and 1,1-diphenyl-1-picrylhydrazyl radical(DPPH). Antioxidant activity was investigated with reducing power method. Pooled human liver microsome was used for investigating the effects on cytochrome P450 1A2 (CYP1A2) catalytic activities by using phenacetin as a substrate. Dixon and Cornish- Bowden plots were used for enzyme kinetic analysis. The EC, OC, BC and PC potentially inhibited superoxide anion, nitric oxide and DPPH radicals. IC50 values of superoxide anion scavenging of EC, OC, BC and PC were 16.42, 79.83, 123.69 and 123.69 μg/ml, respectively. EC was more potent than OC and BC in terms of nitric oxide radical scavenger: IC50 values of EC, OC and BC were 24.16, 37.34 and 52.64 μg/ml, respectively. In addition, the IC50 values of EC, OC, BC and PC on DPPH radical scavenging were 70.00, 184.56, 285.34 and 866.54 μg/ ml, respectively. The IC50 values of EC, OC, BC and PC on phenacetin O-deethylation were 124.98, 111.86, 156.68 and 31.05 μg/ml, respectively. Enzyme kinetics showed that the type of inhibition mechanism was mixed-type. The result of this study shows that caffeic acid ester analogues potentially scavenge free radicals and inhibit catalytic activity of CYP1A2. This may lead to important implications in the prevention of CYP1A2-mediated chemical carcinogenesis.

  合成了乙基咖啡酸酯（EC）、辛基咖啡酸酯（OC）、苄基咖啡酸酯（BC）和苯乙基咖啡酸酯（PC），并评估了它们对超氧阴离子、氮氧自由基和1,1-二苯基-1-苦味唑自由基（DPPH）的清除能力。采用还原力法研究抗氧化活性。使用人类肝微粒体进行研究，以探讨对细胞色素P450 1A2（CYP1A2）催化活性的影响，使用对乙酰氨基酚作为底物。采用Dixon和Cornish-Bowden绘图法进行酶动力学分析。结果表明，EC、OC、BC和PC对超氧阴离子、氮氧和DPPH自由基具有潜在的抑制作用。EC、OC、BC和PC对超氧阴离子清除的IC50值分别为16.42、79.83、123.69和123.69 μg/ml。在氮氧自由基清除方面，EC的活性优于OC和BC，其IC50值分别为24.16、37.34和52.64 μg/ml。此外，EC、OC、BC和PC对DPPH自由基清除的IC50值分别为70.00、184.56、285.34和866.54 μg/ml。EC、OC、BC和PC对对乙酰氨基酚O-去乙基化的IC50值分别为124.98、111.86、156.68和31.05 μg/ml。酶动力学分析表明抑制机制为混合型抑制。该研究结果表明，咖啡酸酯类类化合物可能对自由基具有清除作用，并抑制CYP1A2的催化活性。这可能对预防CYP1A2介导的化学致癌有重要意义。
• Protective Effect of Caffeic Acid Derivatives on tert-Butyl Hydroperoxide-Induced Oxidative Hepato-Toxicity and Mitochondrial Dysfunction in HepG2 Cells
  作者：Tzung-Hsun Tsai、Chun-Hsien Yu、Yu-Ping Chang、Yu-Ting Lin、Ching-Jang Huang、Yueh-Hsiung Kuo、Po-Jung Tsai

  DOI：10.3390/molecules22050702

  日期：——

  Oxidative stress results in structural and functional abnormalities in the liver and is thought to be a crucial factor in liver diseases. The aim of this study was to investigate the cytoprotective and antioxidant effects of caffeic acid (CA) derivatives on tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in HepG2 cells. Nine CA derivatives were synthesized, including N-phenylethyl caffeamide (PECA), N-(3-florophen)methyl caffeamide (FMCA), N-(4-methoxy-phen)methyl caffeamide (MPMCA), N-heptyl caffeamide (HCA), N-octyl caffeamide (OCA), octyl caffeate (CAOE), phenpropyl caffeate (CAPPE), phenethyl caffeate (CAPE), and phenmethyl caffeate (CAPME). The results showed that CA and its derivatives significantly inhibited t-BHP-induced cell death of HepG2 cells. The rank order of potency of the CA derivatives for cytoprotection was CAOE > HCA > OCA > FMCA > CAPPE > CAPME > CAPE > PECA > MPMCA > CA. Their cytoprotective activity was associated with lipophilicity. The antioxidant effect of these compounds was supported by the reduction in the levels of thiobarbituric acid reactive substrates, a biomarker of lipid peroxidation, in HepG2 cells. Pre-treatment of CA derivatives significantly prevented the depletion of glutathione, the most important water-soluble antioxidant in hepatocytes. Pre-treatment of CA derivatives before t-BHP exposure maintained mitochondrial oxygen consumption rate and ATP content in the injured HepG2 cells. CA derivatives except OCA and HCA significantly suppressed t-BHP-induced hypoxia-inducible factor-1α (HIF-1α) protein level. In addition, all of these CA derivatives markedly increased the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation in the nucleus, indicating that their cytoprotection may be mediated by the activation of Nrf2. Our results suggest that CA derivatives might be a hepatoprotective agent against oxidative stress.

  氧化应激导致肝脏结构和功能异常，被认为是肝脏疾病的一个关键因素。本研究的目的是探讨咖啡酸（CA）衍生物在特丁基过氧化氢（t-BHP）诱导的肝HepG2细胞氧化应激中的细胞保护和抗氧化作用。合成了九种CA衍生物，包括N-苯乙基咖啡酰胺（PECA）、N-(3-氟苯)甲基咖啡酰胺（FMCA）、N-(4-甲氧基苯)甲基咖啡酰胺（MPMCA）、N-庚基咖啡酰胺（HCA）、N-辛基咖啡酰胺（OCA）、辛基咖啡酸酯（CAOE）、苯丙基咖啡酸酯（CAPPE）、苯乙基咖啡酸酯（CAPE）和苯甲基咖啡酸酯（CAPME）。结果显示，CA及其衍生物显著抑制了t-BHP诱导的HepG2细胞死亡。CA衍生物的细胞保护效力的排列顺序为CAOE > HCA > OCA > FMCA > CAPPE > CAPME > CAPE > PECA > MPMCA > CA。它们的细胞保护活性与脂溶性相关。这些化合物的抗氧化效果得到了支持，因为它们降低了HepG2细胞中硫代巴比妥酸反应底物的水平，这是脂质过氧化的生物标志物。CA衍生物的预处理显著防止了谷胱甘肽的耗竭，谷胱甘肽是肝细胞中最重要的水溶性抗氧化剂。CA衍生物在t-BHP暴露前的预处理保持了受损HepG2细胞的线粒体氧气消耗率和ATP含量。除OCA和HCA外，CA衍生物显著抑制了t-BHP诱导的缺氧诱导因子-1α（HIF-1α）蛋白水平。此外，所有这些CA衍生物显著增加了核因子红细胞2相关因子2（Nrf2）在细胞核中的积累，表明它们的细胞保护可能是通过激活Nrf2介导的。我们的结果表明，CA衍生物可能是对抗氧化应激的肝保护剂。
• 一种咖啡酸苄酯的制备方法
  申请人：浙江科技学院

  公开号：CN109456183A

  公开（公告）日：2019-03-12

  本发明公开了一种咖啡酸苄酯的制备方法，整体步骤为：a、将咖啡酸溶于有机溶剂中，加入氯化亚砜进行反应，制得中间产物A；b、碱及有机溶剂存在下，将中间产物A与苯甲醇进行反应，制得咖啡酸苄酯，其分子式为本发明首次通过有机化学合成的途径生成了咖啡酸苄酯，弥补了现有技术只能利用天然物质进行提取的空白，具有成本低廉、操作简单、收率高、质量好的优点，尤其适用于大规模工业化生产，实用性非常强。