(3β)-3-ethoxyolean-12-en-28-oic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (3β)-3-ethoxyolean-12-en-28-oic acid
• 英文别名: (4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-ethoxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid
• 化学式: C₃₂H₅₂O₃
• 分子量: 484.763
• InChiKey: JJBKRWWJHLKUEK-DFHVBEEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  35
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  溴乙烷 、 齐墩果酸 在 sodium 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以60%的产率得到(3β)-3-ethoxyolean-12-en-28-oic acid
  参考文献：
  名称：

  Synthesis of oleanolic acid derivatives: In vitro, in vivo and in silico studies for PTP-1B inhibition

  摘要：

  Non-insulin dependent diabetes mellitus is a multifactorial disease that links different metabolic routes: a point of convergence is the enzyme PTP-1B which turns off insulin and leptin receptors involved in glucose and lipid metabolism, respectively. Pentacyclic acid triterpenes such as oleanolic acid (OA) have proved to be excellent PTP-1B inhibitors, thus, the purpose of current work was to generate a series of derivatives that improve the pharmacological effect of OA. Our findings suggest that the presence of the carboxylic acid and/or its corresponding reduction product carbinol derivative (H-bond donor) in C-28 is required to maintain the inhibitory activity: moreover, this is further enhanced by ester or ether formation on C-3. The most active derivatives were cinnamoyl ester (6) and ethyl ether (10). Compound 6 showed potent in vitro inhibitory activity and significantly decrease of blood glucose levels on in vivo experiments. Meanwhile, 10 showed contrasting outcomes, since it was the compound with higher inhibitory activity and selectivity over PTP-1B and has improved interaction with site B, according with docking studies, the in vivo antidiabetic effect was similar to oleanolic acid. In conclusion, oleanolic acid derivatives have revealed an enhanced inhibitory effect over PTP-1B activity by increasing molecular interactions with either catalytic or allosteric sites and producing a hypoglycaemic effect on non insulin dependent diabetes mellitus rat model. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.036

文献信息

• Synthesis of oleanolic acid derivatives: In vitro, in vivo and in silico studies for PTP-1B inhibition
  作者：Juan José Ramírez-Espinosa、Maria Yolanda Rios、Paolo Paoli、Virginia Flores-Morales、Guido Camici、Vianey de la Rosa-Lugo、Sergio Hidalgo-Figueroa、Gabriel Navarrete-Vázquez、Samuel Estrada-Soto

  DOI：10.1016/j.ejmech.2014.09.036

  日期：2014.11

  Non-insulin dependent diabetes mellitus is a multifactorial disease that links different metabolic routes: a point of convergence is the enzyme PTP-1B which turns off insulin and leptin receptors involved in glucose and lipid metabolism, respectively. Pentacyclic acid triterpenes such as oleanolic acid (OA) have proved to be excellent PTP-1B inhibitors, thus, the purpose of current work was to generate a series of derivatives that improve the pharmacological effect of OA. Our findings suggest that the presence of the carboxylic acid and/or its corresponding reduction product carbinol derivative (H-bond donor) in C-28 is required to maintain the inhibitory activity: moreover, this is further enhanced by ester or ether formation on C-3. The most active derivatives were cinnamoyl ester (6) and ethyl ether (10). Compound 6 showed potent in vitro inhibitory activity and significantly decrease of blood glucose levels on in vivo experiments. Meanwhile, 10 showed contrasting outcomes, since it was the compound with higher inhibitory activity and selectivity over PTP-1B and has improved interaction with site B, according with docking studies, the in vivo antidiabetic effect was similar to oleanolic acid. In conclusion, oleanolic acid derivatives have revealed an enhanced inhibitory effect over PTP-1B activity by increasing molecular interactions with either catalytic or allosteric sites and producing a hypoglycaemic effect on non insulin dependent diabetes mellitus rat model. (C) 2014 Elsevier Masson SAS. All rights reserved.