(Z)-2-acetoxy-3-(3,4-methylenedioxyphenyl)acrylic acid | 1162198-85-7

• 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: (Z)-2-acetoxy-3-(3,4-methylenedioxyphenyl)acrylic acid
• 英文别名: (Z)-2-acetyloxy-3-(1,3-benzodioxol-5-yl)prop-2-enoic acid
• CAS: 1162198-85-7
• 化学式: C₁₂H₁₀O₆
• 分子量: 250.208
• InChiKey: SXZRUQBJIJHMTN-WZUFQYTHSA-N

物化性质

• 熔点：
  164-166 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  410.6±45.0 °C(Predicted)
• 密度：
  1.450±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (Z)-2-acetoxy-3-(3,4-methylenedioxyphenyl)acrylic acid 在 10% Pd/C 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 26.25h， 生成 N-((R)-3-benzylthio-1-methoxy-1-oxo-2-propanyl)-3-((3,4-methylenedioxy)phenyl)propanamide
  参考文献：
  名称：

  The synthesis and biological evaluation of novel Danshensu–cysteine analog conjugates as cardiovascular-protective agents

  摘要：

  A series of novel amide and thioester conjugates between Danshensu and cysteine derivatives have been designed and synthesized based on the strategy of "medicinal chemical hybridization". Pharmacological evaluation indicated that the amide conjugates 3a/4a/17a and thioester conjugates 6a-d exhibited obvious protective effects on H2O2-induced human umbilical vein endothelial cells (HUVECs). Pretreated with these conjugates could increase glutathione (GSH) activity and decrease malondialdehyde (MDA) level. Further study on mechanism of compound 4a revealed that it was related to its mitochondrial-protective effect and regulation of apoptosis-related proteins expression (Bax, p53, PARP, caspase-3, caspase-9 and Bcl-2). These results indicate that these Danshensu-cysteine analog conjugates possess significant cardiovascular-protective effects and merit further investigation. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.016
• 作为产物：
  描述：

  β-(benzo[1,3]dioxol-5-yl)-α-acetamidoacrylic acid 在 盐酸 、 乙酸酐 作用下， 以 水 为溶剂， 反应 6.0h， 生成 (Z)-2-acetoxy-3-(3,4-methylenedioxyphenyl)acrylic acid
  参考文献：
  名称：

  The synthesis and biological evaluation of novel Danshensu–cysteine analog conjugates as cardiovascular-protective agents

  摘要：

  A series of novel amide and thioester conjugates between Danshensu and cysteine derivatives have been designed and synthesized based on the strategy of "medicinal chemical hybridization". Pharmacological evaluation indicated that the amide conjugates 3a/4a/17a and thioester conjugates 6a-d exhibited obvious protective effects on H2O2-induced human umbilical vein endothelial cells (HUVECs). Pretreated with these conjugates could increase glutathione (GSH) activity and decrease malondialdehyde (MDA) level. Further study on mechanism of compound 4a revealed that it was related to its mitochondrial-protective effect and regulation of apoptosis-related proteins expression (Bax, p53, PARP, caspase-3, caspase-9 and Bcl-2). These results indicate that these Danshensu-cysteine analog conjugates possess significant cardiovascular-protective effects and merit further investigation. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.016

文献信息

• Asymmetric synthesis and biological evaluation of Danshensu derivatives as anti-myocardial ischemia drug candidates
  作者：Cunnan Dong、Yang Wang、Yi Zhun Zhu

  DOI：10.1016/j.bmc.2009.02.065

  日期：2009.5

  The synthesis and bioactivities of Danshensu derivatives (R)-methyl 2-acetoxy-3-(3,4-diacetoxyphenyl) propanoate (1a), (R)-methyl 2-acetoxy-3-(3,4-methylenedioxyphenyl) propanoate (1b) and their racemates 7 and 10 were reported in this paper. These derivatives were designed to improve their chemical stability and liposolubility by protecting Danshensu's phenolic hydroxyl groups with acetyl or methylene which could be readily hydrolyzed to release bioactive Danshensu. The asymmetric synthesis of 1a and 1b were achieved by catalytic hydrogenation of (Z)-methyl 2-acetoxy-3-(3,4-diacetoxyphenyl)-2-propenoate (6a) and (Z)-methyl 2-acetoxy-3-(3,4-methylenedioxyphenyl)-2-propenoate (6b) in excellent enantiomeric excesses (92% ee and 98% ee, respectively) and good yields (>89%). An unexpected intermediate product, (Z)-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid (4c) was obtained with high chemoselectivity in 86% yield by keeping the reaction temperature at 60 degrees C and its structure was identified by Xray single crystal diffraction analysis. 1a, 1b and their racemates 7, 10 as well as 4c exhibited potent protective activities against hypoxia-induced cellular damage. The in vitro test showed that all these compounds could increase cell viability, and inhibit lipid hyperoxidation. Furthermore, 1a and 4c could inhibit apoptosis by regulating the expression of apoptosis-related molecule in gene and protein levels, up-regulating the expression of bcl-2 and down-regulating bax and caspase-3. The in vivo test indicated that 4c exhibited anti-myocardial ischemic effects featured by reducing infarction size and increasing the level of the intracellular enzymes detectable in serum. Therefore, these Danshensu derivatives may be good drug candidates for anti-myocardial ischemia therapy and merit further investigation. (C) 2009 Elsevier Ltd. All rights reserved.