(E)-3-(2,4,6-trimethoxyphenyl)acrylic acid

• 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: (E)-3-(2,4,6-trimethoxyphenyl)acrylic acid
• 英文别名: 2,4,6-Trimethoxycinnamic acid；(E)-3-(2,4,6-trimethoxyphenyl)prop-2-enoic acid
• 化学式: C₁₂H₁₄O₅
• mdl: MFCD00016838
• 分子量: 238.24
• InChiKey: NCPKRIPFNFIXOK-SNAWJCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-3-(2,4,6-trimethoxyphenyl)acrylic acid 在 草酰氯 作用下， 以 二氯甲烷 为溶剂， 生成 2,4,6-trimethoxycynnamoyl chloride
  参考文献：
  名称：

  Synthesis and photostability of methoxycinnamic acid modified cyclodextrins

  摘要：

  Various cyclodextrins, alpha, beta and gamma, were esterified with 4-methoxy-, 2,4,5- and 2,4,6-trimethoxycinnamic acids. Upon esterification with beta-cyclodextrin, the photostability of 2,4,5-trimethoxycinnamate increased while no improvement was observed for 4-methoxycinnamate and 2,4,6-trimethoxycinnamate. However, increase in the photostability of 4-methoxycinnamoyl moiety could be observed when esterified with alpha-CD and that of 2,4,6-trimethoxycinnamoyl moiety could be observed after being esterified with gamma-CD. These photostability data together with the 2D NMR analyses indicated that the 4-methoxycinnamoyl, 2,4,5-trimethoxycinnamoyl and 2,4,6-trimethoxy cinnamoyl moieties could enter the alpha-CD, the beta-CD, and the gamma-CD cavities, respectively. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jphotochem.2010.03.016
• 作为产物：
  描述：

  (E)-3-(2,4,6-trimethoxy-phenyl)-acrylic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以81.8%的产率得到(E)-3-(2,4,6-trimethoxyphenyl)acrylic acid
  参考文献：
  名称：

  远志-Acori tatarinowii草药对对取代肉桂酸α-asaronol酯的启发：设计，合成，抗惊厥活性和抑制乳酸脱氢酶的研究。

  摘要：

  受中药对远志治疗癫痫症的启发，结合中药分子化学（CTCMMC）策略设计了33种新型取代肉桂酸α-细辛醇酯及其类似物，不仅对抗惊厥药进行了系统合成和测试，在三种小鼠模型中具有活性，但对LDH的抑制活性也很高。其中，68-70和75表现出出色的抗惊厥活性谱，且具有适度的预防神经性疼痛的能力，并且神经毒性低。这四种化合物的保护指数均与替比妥醇，拉考酰胺，卡马西平和丙戊酸相比具有优势。68-70表现出良好的LDH1和LDH5抑制活性，且具有非竞争性抑制类型，并且比替替戊醇更有效。值得注意的是70 作为代表剂，也显示为对人α1β2γ2GABAA受体（EC50 46.3±7.3μM）的中等正变构调节剂。因此，有68-70种药物有望发展成为抗癫痫药，特别是用于治疗难治性癫痫病（例如Dravet综合征）。

  DOI：

  10.1016/j.ejmech.2019.111650

文献信息

• Glycosylation of acids under phase transfer conditions. Partial synthesis of saponins
  作者：Christophe Bliard、Georges Massiot、Serge Nazabadioko

  DOI：10.1016/0040-4039(94)88088-3

  日期：1994.8

  β-D-glycosyl esters are prepared in high yields by reaction of various carboxylic acids and acetobromosugars. The reaction uses potassium carbonate under phase tranfer conditions. Deacetylation affords the β-D-glycosyl carboxylates.

  通过各种羧酸与乙酰溴糖的反应，可以高产率制备β-D-糖基酯。反应在相转移条件下使用碳酸钾。脱乙酰基得到β-D-糖基羧酸盐。
• Synthesis and structure-activity relationship studies of parthenolide derivatives as potential anti-triple negative breast cancer agents
  作者：Weizhi Ge、Xin Hao、Fangzhi Han、Zhongquan Liu、Tianpeng Wang、Mengmeng Wang、Ning Chen、Yahui Ding、Yue Chen、Quan Zhang

  DOI：10.1016/j.ejmech.2019.01.058

  日期：2019.3

  Triple-negative breast cancer (TNBC) is the most aggressive cancers with a high recurrence rate and rapidly acquired drug resistance among various breast cancer subtypes. There is no specific drug for treatment of TNBC. Discovery of therapeutic agents with unique modes of actions is urgently needed. In this study, a series of seventy parthenolide derivatives was designed, synthesized, and evaluated

  三阴性乳腺癌（TNBC）是最激进的癌症，其复发率高且在各种乳腺癌亚型中迅速获得耐药性。没有用于治疗TNBC的特定药物。迫切需要发现具有独特作用方式的治疗剂。在这项研究中，设计，合成和评估了一系列七十种单烯菊酯衍生物的抗TNBC活性。化合物7d对不同的乳腺癌细胞表现出最有效的活性，IC 50值在0.20μM至0.27μM范围内，与母体化合物小白菊内酯的IC 50值在2.68–4.63μM相比，提高了11.6至18.6倍。。值得一提的是7d比阳性对照药物ADR更活跃。此外，化合物7d可通过线粒体途径诱导SUM-159细胞凋亡，并引起SUM-159细胞G1期阻滞。这些发现表明，化合物7d作为最终发现有效的抗TNBC药物的先导化合物值得进一步研究。
• Discovery of caffeic acid phenethyl ester derivatives as novel myeloid differentiation protein 2 inhibitors for treatment of acute lung injury
  作者：Lingfeng Chen、Yiyi Jin、Hongjin Chen、Chuchu Sun、Weitao Fu、Lulu Zheng、Min Lu、Pengqin Chen、Gaozhi Chen、Yali Zhang、Zhiguo Liu、Yi Wang、Zengqiang Song、Guang Liang

  DOI：10.1016/j.ejmech.2017.11.066

  日期：2018.1

  Myeloid differentiation protein 2 (MD2) is an essential molecule which recognizes lipopolysaccharide (LPS), leading to initiation of inflammation through the activation of Toll-like receptor 4 (TLR4) signaling. Caffeic acid phenethyl ester (CAPE) from propolis of honeybee hives could interfere interactions between LPS and the TLR4/MD2 complex, and thereby has promising anti-inflammatory properties

  髓样分化蛋白2（MD2）是识别脂多糖（LPS）的必需分子，可通过激活Toll样受体4（TLR4）信号传导引发炎症。蜜蜂蜂巢蜂胶中的咖啡酸苯乙酯（CAPE）可能会干扰LPS与TLR4 / MD2复合物之间的相互作用，因此具有令人振奋的抗炎特性。在这项研究中，我们设计和合成了48种CAPE衍生物，并评估了它们在LPS激活的小鼠初级腹膜巨噬细胞（MPM）中的抗炎活性。发现活性最高的化合物10s以高亲和力与MD2结合，从而阻止了LPS / MD2 / TLR4复合物的形成。10s的结合模式揭示了与MD2的主要相互作用是通过两个关键的氢键和疏水相互作用建立的。此外，10s在体内对LPS引起的ALI（急性肺损伤）显示出显着的保护作用。综上所述，这项工作为开发抗炎药提供了新的先导结构和候选药物MD2抑制剂。
• CINNAMIC ACID ASCORBATES
  申请人：Rudolph Thomas

  公开号：US20120052028A1

  公开（公告）日：2012-03-01

  The invention relates to specific cinnamic acid ascorbates and to the use thereof as UV filters which bond to the skin, and to a process for the preparation thereof, and to preparations comprising these compounds.

  本发明涉及特定的肉桂酸抗坏血酸盐，并将其用作与皮肤结合的紫外线过滤剂，以及其制备过程和包含这些化合物的制剂。
• Synthesis, mitochondrial localization of fluorescent derivatives of cinnamamide as anticancer agents
  作者：Kun Yang、Yuanyuan Li、Qun Tang、Lifang Zheng、Dian He

  DOI：10.1016/j.ejmech.2019.03.001

  日期：2019.5

  Mitochondria are considered as a therapeutic target for new drug design toward all kinds of cancer. Hence in order to enhance the dosage in mitochondrial fraction of cinnamamides, the mitochondria targeted derivatives were designed by the incorporation of cinnamamides into a fluorophore carrier of coumarin-3-carboxamide with a 1:1 stoichiometry. Using the amide linkers, twenty-one compounds were synthesized and the cytotoxicity against a panel of cancer cells (MCF-7, Hela, HepG2, HL-60) was tested. In particular, compound 18c displayed the potent cytotoxicity toward HL-60 leukaemia cells, which could quickly and efficiently entry into HL-60 cells and specifically localize within mitochondria. And 18c preferred enrichment in HL-60 cells than in PBMC normal cells, accounting for the higher toxicity to cancer cells than to normal cells. Moreover, the dissipations of mitochondrial membrane potential and enhancement of cellular ROS level were also preceded upon 18c treatment, leading to cell cycle arrest and apoptosis/necrosis in HL-60 cells. Besides, acted as a Michael acceptor, 18c initiated a thia-Michael addition reaction toward cysteamine (1:2 stoichiometry), detecting by the UV-Vis spectrum and HRMS analysis. This could result in the blue emission of 18c in mitochondria after the procedure of cell fixation, owing to the formation of covalent bond with mitochondrial thiols. Our study reported 18c might be useful for the further development into a mitochondria-targeted anti-leukemia agent and the Michael acceptor might be a versatile functional group. (C) 2019 Elsevier Masson SAS. All rights reserved.