N-(L-valine)-3β-hydroxy-11-oxo-olean-12-en-18β-H-30-amide | 708199-60-4

• 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: N-(L-valine)-3β-hydroxy-11-oxo-olean-12-en-18β-H-30-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-methylbutanoic acid
• CAS: 708199-60-4
• 化学式: C₃₅H₅₅NO₅
• 分子量: 569.825
• InChiKey: LWCAIISOTZCUOL-WMCYLTHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  41
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.86
• 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：

  N-(L-valine)-3β-hydroxy-11-oxo-olean-12-en-18β-H-30-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46%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 N-(L-valine)-3β-hydroxy-11-oxo-olean-12-en-18β-H-30-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 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.