trans-2,4,5-trimethoxycinnamic acid ethyl ester | 14469-89-7

• 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: trans-2,4,5-trimethoxycinnamic acid ethyl ester
• 英文别名: ethyl 3-(2,4,5-trimethoxyphenyl)-prop-2-enoate；(E)-ethyl 2,4,5-trimethoxylcinnamate；ethyl(2,4,5-trimethoxy)cinnamate；Ethyl (E)-3-(2,4,5-trimethoxyphenyl)acrylate；ethyl (E)-3-(2,4,5-trimethoxyphenyl)prop-2-enoate
• CAS: 14469-89-7；80152-43-8
• 化学式: C₁₄H₁₈O₅
• 分子量: 266.294
• InChiKey: GARBMEJSXPWEOM-VOTSOKGWSA-N

物化性质

• 熔点：
  68-69 °C
• 沸点：
  398.5±37.0 °C(Predicted)
• 密度：
  1.114±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  trans-2,4,5-trimethoxycinnamic acid ethyl ester 在 二异丁基氢化铝 、 三乙胺 、 lithium hexamethyldisilazane 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 5.75h， 生成 (E)-N-(1-(2,4,5-trimethoxyphenyl)hexa-1,5-dien-3-yl)acrylamide
  参考文献：
  名称：

  Synthesis of methoxylated goniothalamin, aza-goniothalamin and γ-pyrones and their in vitro evaluation against human cancer cells

  摘要：

  The present work describes the preparation of three novel series of compounds based on the structure of goniothalamin, a natural styryl lactone which has been found to display cytotoxic and antiproliferative activities against a variety of cancer cell lines. A focused library of 29 novel goniothalamin analogues was prepared and evaluated against seven human cancer cell lines. While the gamma-pyrones and the azagoniothalamin analogues were less potent than the lead compound, 2,4-dimethoxy analogue 88 has shown to be more potent in vitro than goniothalamin against all cancer cell lines evaluated. Furthermore, it was more potent than doxorubicin against NCI-ADR/RES, OVCAR-03 and HT-29 while being less toxic to human keratinocytes (HaCat). The 3,5-dimethoxy analogue 90 and 2,4,5-trimethoxy analogue 92 also displayed promising antiproliferative activity when compared to goniothalamin ( 1). These results provide new elements for the design and synthesis of novel representatives of this family of natural compounds. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.03.059
• 作为产物：
  描述：

  2,4,5-trimethoxycinnamic acid 、 氯甲酸乙酯 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 0.17h， 以88%的产率得到trans-2,4,5-trimethoxycinnamic acid ethyl ester
  参考文献：
  名称：

  微波加速酯化的α，β在乙腈不饱和酸与烷基或芳基甲酸酯-三乙胺新型酯化试剂混合物†

  摘要：

  通过用烷基或芳基碳氯化物，三乙胺和乙腈处理相应的酸，在微波辐射下第一次完成10分钟，可以有效合成α，β-不饱和酯。分离出酯1b - 24b的产率为71-97％。

  DOI：

  10.1002/hlca.200590058

文献信息

• Ethyl Cinnamate Derivatives as Promising High-Efficient Acaricides against <i>Psoroptes cuniculi</i>: Synthesis, Bioactivity and Structure–Activity Relationship
  作者：Bingyu Zhang、Chao Lv、Weibo Li、Zhiming Cui、Dongdong Chen、Fangjun Cao、Fang Miao、Le Zhou

  DOI：10.1248/cpb.c14-00765

  日期：——

  This paper reported the synthesis, structure–activity relationship (SAR) and acaricidal activity in vitro against Psoroptes cuniculi, a mange mite, of 25 ethyl cinnamate derivatives. All target compounds were synthesized and elucidated by means of MS, 1H- and 13C-NMR analysis. The results showed that 24 out of 25 tested compounds at 1.0 mg/mL demonstrated acaricidal activity in varying degrees. Among them, 6, 15, 26, 27 and 30 showed significant activity with median lethal concentration values (LC50) of 89.3, 119.0, 39.2, 29.8 and 41.2 µg/mL, respectively, which were 2.1- to 8.3-fold the activity of ivermectin (LC50=247.4 µg/mL), a standard drug in the treatment of Psoroptes cuniculi. Compared with ivermectin, with a median lethal time value (LT50) of 8.9 h, 27 and 30 showed smaller LT50 values of 7.9 and 1.3 h, respectively, whereas 6, 15 and 26 showed slightly larger LT50 values of 10.6, 11.0 and 10.4 h at 4.5 µmol/mL. SARs showed that the presence of o-NO2 or m-NO2 on the benzene ring significantly improved the activity, whereas the introduction of a hydroxy, methoxy, acetoxy, methylenedioxy, bromo or chloro group reduced the activity. (E)-Cinnamates were more effective than their (Z)-isomer. Nevertheless, the carbon–carbon double bond in the acrylic ester moiety was proven not to be essential to improve the activity of cinnamic acid esters. Thus, the results strongly indicate that cinnamate derivatives, especially their dihydro derivatives, should be promising candidates or lead compounds for the development of novel acaricides for the effective control of animal or human acariasis.

  本研究报道了25种肉桂酸乙酯衍生物的合成、构效关系及其对兔疥螨的杀螨活性。所有目标化合物通过MS、1H-和13C-NMR进行了表征。结果表明,25个化合物中有24个在1.0mg/mL浓度下表现出不同程度的杀螨活性。其中,6、15、26、27和30号化合物显示出显著的活性,半数致死浓度值(LC50)分别为89.3、119.0、39.2、29.8和41.2μg/mL,分别是伊维菌素(LC50=247.4μg/mL)的2.1-8.3倍。与伊维菌素(半数致死时间LT50为8.9h)相比,27和30号化合物的LT50值更小,分别为7.9h和1.3h,而6、15和26号化合物的LT50值稍大,分别为10.6、11.0和10.4h(4.5μmol/mL)。构效关系表明,苯环上的邻硝基或间硝基显著提高了活性,而引入羟基、甲氧基、乙酰氧基、亚甲二氧基、溴或氯则降低了活性。(E)-肉桂酸酯比其(Z)-异构体更有效。然而,丙烯酸酯部分的碳-碳双键对于提高肉桂酸酯的活性并非必需。因此,结果强烈表明,肉桂酸酯衍生物,尤其是其二氢衍生物,应该是开发新型杀螨剂以有效控制人和动物螨病的极具潜力的候选物或先导化合物。
• α-细辛醇及其制备方法与应用
  申请人：西北大学

  公开号：CN104529724B

  公开（公告）日：2016-11-02

  本发明涉及α‑细辛醇及其制备方法与应用。所涉及的α‑细辛醇如结构式I。所涉及的制备方法包括2,4,5‑三甲氧基苯甲醛与丙二酸亚异丙酯(麦氏酸，meldrum's acid)、脂肪醇在吡啶与哌啶的催化下脱羧得到反式2,4,5‑三甲氧基肉桂酸酯，再经还原剂还原得到α‑细辛醇。本发明制备方法简单，产率较高。所涉及的应用是α‑细辛醇用于制备镇静、安神、抗老年痴呆、抗惊厥、抗癫痫或保护心脑血管药物的应用。
• Pilot-Scale Synthesis and Purification of α-Asaronol for Antiepileptic Drug Development
  作者：Qun-Zheng Zhang、Zhi-Qiang Ouyang、Yu-Hao Zhou、Si-Chang Wang、Cong-Yu Ke、Ya-Jun Bai、Xun-Li Zhang、Xiao-Hui Zheng

  DOI：10.1021/acs.oprd.3c00076

  日期：2023.7.21

  impurities in the synthesis process, namely, (2,4,5-trimethoxyphenyl)methanol, 3-(2,4,5-trimethoxyphenyl)propan-1-ol, 5,5′-((1E,1′E)-oxybis(prop-1-ene-3,1-diyl)) bis(1,2,4-trimethoxybenzene), and diethyl 2-(2,4,5-trimethoxybenzyl)malonate. By adapting a commonly used recrystallization process through optimization, a large-scale purification method was developed for the purification of α-asaronol, achieving

  开发了一种简单高效的中试工艺来合成和纯化 α-细辛醇（( E )-3'-羟基细辛醚）。以2,4,5-三甲氧基苯甲醛1和丙二酸氢乙酯2为原料，通过Knoevenagel缩合反应生成中间体(E)-3-(2,4,5-三甲氧基苯基)丙烯酸乙酯3(收率93.3%)，然后用二异丁基铝还原，一批生产4.29kgα-细辛醇4(纯度99.92 % )氢化物生成α-细辛醇4收率89.2%。液相色谱-质谱(LC-MS)和核磁共振(NMR)光谱分析显示合成过程中存在四种主要杂质，即(2,4,5-三甲氧基苯基)甲醇、3-(2,4,5-三甲氧基苯基)丙-1-醇、5,5′-((1 E ,1′ E )-氧双(丙-1-烯-3,1-二基))双(1,2,4-三甲氧基苯)和2-(2,4,5-三甲氧基苄基)丙二酸二乙酯。通过优化采用常用的重结晶工艺，开发了α-细辛醇的大规模纯化方法，重结晶纯度达到99.92%。该中试研究为候选药物
• Jalander, Lars, Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry, 1981, vol. 35, # 6, p. 419 - 428
  作者：Jalander, Lars

  DOI：——

  日期：——
• DDQ-Catalyzed Oxidative C(sp³)–H Functionalization of Aryltetralins and Subsequent Chemoselective Oxidative Demethylation to Access Dihydronaphthalenes and Dihydronaphthoquinones
  作者：Dileep Kumar、Abdus Salam、Tonish Kumar Sahu、Sujit Soumitra Sahoo、Tabrez Khan

  DOI：10.1021/acs.joc.1c01780

  日期：2021.11.5