(R)-methyl 2-acetoxy-3-(3,4-methylenedioxyphenyl)-propanoate | 1162198-87-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (R)-methyl 2-acetoxy-3-(3,4-methylenedioxyphenyl)-propanoate
• 英文别名: methyl (2R)-2-acetyloxy-3-(1,3-benzodioxol-5-yl)propanoate
• CAS: 1162198-87-9
• 化学式: C₁₃H₁₄O₆
• 分子量: 266.251
• InChiKey: TZLNDMBCYJUFMD-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (Z)-methyl 2-acetoxy-3-(3,4-methylenedioxyphenyl)-acrylate 在 bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate 、 C₃₆H₃₂N₃O₃P 、 氢气 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、6.08 MPa 条件下， 反应 24.0h， 以89%的产率得到(R)-methyl 2-acetoxy-3-(3,4-methylenedioxyphenyl)-propanoate
  参考文献：
  名称：

  Asymmetric synthesis and biological evaluation of Danshensu derivatives as anti-myocardial ischemia drug candidates

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2009.02.065

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.