[(2S-3-phenylpropanoic acid)yl]-3β-hydroxy-11-oxoolean-12-en-29-amide | 51298-47-6

• 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: [(2S-3-phenylpropanoic acid)yl]-3β-hydroxy-11-oxoolean-12-en-29-amide
• 英文别名: (2S)-2-[[(2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-10-hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carbonyl]amino]-3-phenylpropanoic acid
• CAS: 51298-47-6
• 化学式: C₃₉H₅₅NO₅
• 分子量: 617.869
• InChiKey: TVTADLXWMMGJAB-VPMONRNISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  45
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(2S-3-phenylpropanoic acid)yl]-3β-hydroxy-11-oxoolean-12-en-29-amide 、 3-氨基-2,2,5,5-四甲基-1-吡咯烷酮 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以54%的产率得到
  参考文献：
  名称：

  Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives

  摘要：

  Eighteen novel spin-labeled 18 beta-glycyrrhetinic acid (GA) derivatives were designed, synthesized, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU-145, KB and KBvin). Most of the derivatives showed more significant cytotoxicity than that of the parent compound GA. The best compound, 6j, with a tryptophan amino moiety and piperidine nitroxyl radical showed GI(50) values of 13.7-15.0 mu M, and was fivefold more potent than GA. In a mechanism of action study, compound 7a was confirmed as a 20S proteasome inhibitor in both in vitro and cell-based assays. These findings support further optimization efforts based on 18 beta-GA as a lead compound to develop potential anticancer drug candidates. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.041
• 作为产物：
  描述：

  甘草次酸 在 N-甲基吗啉 、 吡啶 、 氯化亚砜 、 三氟乙酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 33.0h， 生成 [(2S-3-phenylpropanoic acid)yl]-3β-hydroxy-11-oxoolean-12-en-29-amide
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Amino-Acid Conjugates of Glycyrrhetic Acid

  摘要：

  甘草次酸（GLA）与氨基酸（L-异亮氨酸、-亮氨酸、-缬氨酸和-苯丙氨酸）的共轭物通过酸氯化物法合成，使用酸的甲酯或叔丁酯作为原料。在MDCK细胞培养实验中，GLA与苯丙氨酸的共轭物显示出对甲型流感H1N1/pdm09病毒的高抗病毒活性（ED50 = 4.4 μg/mL，SI = 161）。

  DOI：

  10.1007/s10600-014-0990-0

文献信息

• Synthesis and in vitro/in vivo anticancer evaluation of pentacyclic triterpenoid derivatives linked with -phenylalanine or -proline
  作者：Yudong Yin、Lixin Sheng、Juzheng Zhang、Liqiong Zhang、Jingjing Liu、Xiaoan Wen、Yanghan Liu、Yang Si、Keguang Cheng

  DOI：10.1016/j.bioorg.2022.105865

  日期：2022.9

  Extensive research effort has been put in pentacyclic triterpenoids due to their numerous biological activities. However, their poor water solubility and low oral bioavailability limit their antitumor effects in vivo. To address these issues, 37 triterpenoid acid derivatives linked to l-phenylalanine or l-proline were designed and synthesized in this study. Structure-activity relationship (SAR) studies

  由于五环三萜类化合物具有多种生物活性，因此对其进行了广泛的研究。然而，它们的水溶性差和口服生物利用度低限制了它们在体内的抗肿瘤作用。为了解决这些问题，本研究设计并合成了37 种与l-苯丙氨酸或l-脯氨酸相连的三萜酸衍生物。构效关系 (SAR) 研究发现了两种有前景的甘草次酸 (GA) 衍生物11和16。化合物11是通过 C3-OH 酯化和用l-苯丙氨酸修饰 C30-COOH 获得的，而化合物16是通过将 C3-OH 与l连接获得的-苯丙氨酸。在细胞测定中，与天然存在的 GA的 IC 50值相比，化合物11和16分别表现出高达 48 和 120 倍的改进。荧光显微镜和流式细胞仪分析表明，化合物11和16均增加了癌细胞中 ROS 和 Ca 2+的含量，降低了线粒体膜电位（JC-1），并激活了调节因子 caspase-3/8/9 以触发细胞细胞凋亡。RNA-seq 分析和蛋白质印迹分析表明，化合
• Synthesis and Antiviral Activity of Amino-Acid Conjugates of Glycyrrhetic Acid
  作者：L. A. Baltina、M. V. Khudobko、L. R. Mikhailova、L. A. Baltina、V. A. Fedorova、Ya. A. Orshanskaya、V. V. Zarubaev、O. I. Kiselev

  DOI：10.1007/s10600-014-0990-0

  日期：2014.7

  Conjugates of glycyrrhetic acid (GLA) with amino acids (L-isoleucine, -leucine, -valine, and -phenylalanine) were synthesized by the acid-chloride method using methyl or tert-butyl esters of the acids. Tests in MDCK cell culture showed that the GLA conjugate with phenylalanine exhibited high antiviral activity against influenza A/H1N1/pdm09 virus (ED50 = 4.4 μg/mL, SI = 161).

  甘草次酸（GLA）与氨基酸（L-异亮氨酸、-亮氨酸、-缬氨酸和-苯丙氨酸）的共轭物通过酸氯化物法合成，使用酸的甲酯或叔丁酯作为原料。在MDCK细胞培养实验中，GLA与苯丙氨酸的共轭物显示出对甲型流感H1N1/pdm09病毒的高抗病毒活性（ED50 = 4.4 μg/mL，SI = 161）。
• Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives
  作者：Yingqian Liu、Keduo Qian、Chih-Ya Wang、Chin-Ho Chen、Xiaoming Yang、Kuo-Hsiung Lee

  DOI：10.1016/j.bmcl.2012.10.041

  日期：2012.12

  Eighteen novel spin-labeled 18 beta-glycyrrhetinic acid (GA) derivatives were designed, synthesized, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU-145, KB and KBvin). Most of the derivatives showed more significant cytotoxicity than that of the parent compound GA. The best compound, 6j, with a tryptophan amino moiety and piperidine nitroxyl radical showed GI(50) values of 13.7-15.0 mu M, and was fivefold more potent than GA. In a mechanism of action study, compound 7a was confirmed as a 20S proteasome inhibitor in both in vitro and cell-based assays. These findings support further optimization efforts based on 18 beta-GA as a lead compound to develop potential anticancer drug candidates. (C) 2012 Elsevier Ltd. All rights reserved.