2beta-羟基熊果酸 | 87205-98-9

• 物质功能分类: 生物化工 - 中草药成分
• 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
• 中文名称: 2beta-羟基熊果酸
• 中文别名: (2beta,3beta)-2,3-二羟基乌苏-12-烯-28-酸；2beta-羟基熊果酸;(2beta,3beta)-2,3-二羟基乌苏-12-烯-28-酸
• 英文名称: 2-epi-corosolic acid
• 英文别名: 2beta-Hydroxyursolic acid；(1S,2R,4aS,6aR,6aS,6bR,8aR,10R,11S,12aR,14bS)-10,11-dihydroxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid
• CAS: 87205-98-9
• 化学式: C₃₀H₄₈O₄
• 分子量: 472.709
• InChiKey: HFGSQOYIOKBQOW-XOYVNYDSSA-N

物化性质

• 熔点：
  284 °C (decomp)
• 沸点：
  573.3±50.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  34
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2beta-羟基熊果酸 在 盐酸 、 4-二甲氨基吡啶 、 水 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 49.25h， 生成 N-[2β,3β-diacetyloxy-17β-amino-28-norurs-12-en-17-yl]phenylurea
  参考文献：
  名称：

  Urea derivates of ursolic, oleanolic and maslinic acid induce apoptosis and are selective cytotoxic for several human tumor cell lines

  摘要：

  2,3-Di-O-acetyl-maslinic acid benzylamide (5) has previously been shown to possess high cytotoxicity for a variety of human tumor cell lines while being of low cytotoxicity to non-malignant cells. Structural modifications performed on 5 revealed that the presence of these acetyl groups in 5 and the presence of (2 beta,3 beta)-configurated centers seems necessary for obtaining high cytotoxicity combined with best selectivity between malignant cells and non-malignant mouse fibroblasts. Compounds carrying an ursane skeleton showed weaker cytotoxicity than their oleanane derived analogs. In addition, the benzylamide function in compound 5 should be replaced by a phenylurea moiety to gain better cytotoxicity while retaining and improving the selectivity. Thus, maslinic acid derived N-[2 beta,3 beta-di-O-acetyl-17 beta-amino-28-norolean-12-en-17-yliphenylurea (45) gave best results showing EC50 = 0.9 mu M (for A2780 ovarian cancer cells) with EC50 > 120 mu M for fibroblasts (NIH 3T3) and triggered apoptosis while caspase-3 was not activated by this compound. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.051
• 作为产物：
  描述：

  2-hydroxy-3-oxo-ursa-1,12-dien-28-oic acid 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 以3.7 g的产率得到2beta-羟基熊果酸
  参考文献：
  名称：

  Urea derivates of ursolic, oleanolic and maslinic acid induce apoptosis and are selective cytotoxic for several human tumor cell lines

  摘要：

  2,3-Di-O-acetyl-maslinic acid benzylamide (5) has previously been shown to possess high cytotoxicity for a variety of human tumor cell lines while being of low cytotoxicity to non-malignant cells. Structural modifications performed on 5 revealed that the presence of these acetyl groups in 5 and the presence of (2 beta,3 beta)-configurated centers seems necessary for obtaining high cytotoxicity combined with best selectivity between malignant cells and non-malignant mouse fibroblasts. Compounds carrying an ursane skeleton showed weaker cytotoxicity than their oleanane derived analogs. In addition, the benzylamide function in compound 5 should be replaced by a phenylurea moiety to gain better cytotoxicity while retaining and improving the selectivity. Thus, maslinic acid derived N-[2 beta,3 beta-di-O-acetyl-17 beta-amino-28-norolean-12-en-17-yliphenylurea (45) gave best results showing EC50 = 0.9 mu M (for A2780 ovarian cancer cells) with EC50 > 120 mu M for fibroblasts (NIH 3T3) and triggered apoptosis while caspase-3 was not activated by this compound. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.051

文献信息

• Naturally Occurring Pentacyclic Triterpenes as Inhibitors of Glycogen Phosphorylase: Synthesis, Structure−Activity Relationships, and X-ray Crystallographic Studies
  作者：Xiaoan Wen、Hongbin Sun、Jun Liu、Keguang Cheng、Pu Zhang、Liying Zhang、Jia Hao、Luyong Zhang、Peizhou Ni、Spyros E. Zographos、Demetres D. Leonidas、Kyra-Melinda Alexacou、Thanasis Gimisis、Joseph M. Hayes、Nikos G. Oikonomakos

  DOI：10.1021/jm8000949

  日期：2008.6.1

  Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity ( 7, 18- 20) or no activity ( 21, 22). These saponins, however, might find their value as potential

  二十五个天然存在的五环三萜，在本研究中合成了十五个，被生物评估为兔肌肉糖原磷酸化酶α（GPa）的抑制剂。根据SAR研究，三萜皂苷中糖部分的存在导致活性显着降低（7、18-20）或无活性（21、22）。但是，这些皂苷可能具有潜在的天然前药价值，它们的水溶性比其相应的糖苷配基要高得多。为了阐明GP抑制的机制，我们确定了GPb-亚硫酸和GPb-山梨酸复合物的晶体结构。X射线分析表明，抑制剂在生理活化剂AMP结合的变构活化剂位点结合。
• Selective killing of cancer cells with triterpenoic acid amides - The substantial role of an aromatic moiety alignment
  作者：Sven Sommerwerk、Lucie Heller、Julia Kuhfs、René Csuk

  DOI：10.1016/j.ejmech.2016.06.053

  日期：2016.10

  2,3-Di-O-acetyl-triterpenoic acid derived amides possessing a (2β, 3β) configuration in ring A and two acetyl groups were previously shown to possess high cytotoxicity for human tumor cell lines but to exhibit low cytotoxicity for non-malignant mouse fibroblasts. In this study, augustic acid (1) and 2-epi-corosolic acid (2) were chosen as starting points for the synthesis of analogs. While augustic

  先前显示在环A中具有（2β，3β）构型和两个乙酰基的2,3-二-O-乙酰基-三萜酸衍生的酰胺对人肿瘤细胞系具有高细胞毒性，但对非恶性肿瘤则显示出低细胞毒性小鼠成纤维细胞。在这项研究中，选择了奥古斯丁酸（1）和2-表-硬脂酸（2）作为合成类似物的起点。尽管从丁二酸中衍生出的3-喹啉基酰胺9在SRB分析中的EC 50值较低，但对所有细胞系均具有细胞毒性，而异构体4-异喹啉基酰胺21对肿瘤细胞系具有极强的细胞毒性，但对小鼠成纤维细胞NIH 3T3的细胞毒性却明显较低。此外，积雪草酸的三乙酰化4-异喹啉基衍生物（28）的EC 50  = 80 nM（对于A2780卵巢癌细胞）。如其他实验所示（ac啶橙/碘化丙啶染色，荧光光谱和细胞周期研究），这些化合物主要通过细胞凋亡发挥作用。
• Pentacyclic triterpenes. Part 5: Synthesis and SAR study of corosolic acid derivatives as inhibitors of glycogen phosphorylases
  作者：Xiaoan Wen、Jun Xia、Keguang Cheng、Liying Zhang、Pu Zhang、Jun Liu、Luyong Zhang、Peizhou Ni、Hongbin Sun

  DOI：10.1016/j.bmcl.2007.08.057

  日期：2007.11

  The synthesis and biological evaluation of corosolic acid derivatives and related compounds as inhibitors of rabbit muscle glycogen phosphorylase a is described. Within this series of compounds, 8 (IC(50)=7.31 microM), 12d (IC(50)=3.26 microM), and 12e (IC(50)=5.1 microM) exhibited more potent activities than the parent compound 1 (IC(50)=20 microM). SAR of these compounds is also discussed.

  描述了作为兔肌肉糖原磷酸化酶α抑制剂的钴酸衍生物和相关化合物的合成和生物学评估。在这一系列化合物中，8（IC（50）= 7.31 microM），12d（IC（50）= 3.26 microM）和12e（IC（50）= 5.1 microM）表现出比母体化合物1（IC （50）= 20 microM）。还讨论了这些化合物的SAR。
• [EN] METHODS OF USING INHIBITORS OF ROR?T TO TREAT DISEASE<br/>[FR] PROCÉDÉS D'UTILISATION D'INHIBITEURS DE ROR?T POUR TRAITER UNE MALADIE
  申请人：UNIV TEXAS

  公开号：WO2012145254A2

  公开（公告）日：2012-10-26

  Ursolic acid ("UA") and analogs of UA are taught as RORϒt inhibitors useful in the treatment of a diseases or conditions ameliorated by the expression or production of IL-17, IL-17F, IL-21, and IL-22, and the differentiation and/or development of TH17 cells.
• Urea derivates of ursolic, oleanolic and maslinic acid induce apoptosis and are selective cytotoxic for several human tumor cell lines
  作者：Sven Sommerwerk、Lucie Heller、Julia Kuhfs、René Csuk

  DOI：10.1016/j.ejmech.2016.04.051

  日期：2016.8

  2,3-Di-O-acetyl-maslinic acid benzylamide (5) has previously been shown to possess high cytotoxicity for a variety of human tumor cell lines while being of low cytotoxicity to non-malignant cells. Structural modifications performed on 5 revealed that the presence of these acetyl groups in 5 and the presence of (2 beta,3 beta)-configurated centers seems necessary for obtaining high cytotoxicity combined with best selectivity between malignant cells and non-malignant mouse fibroblasts. Compounds carrying an ursane skeleton showed weaker cytotoxicity than their oleanane derived analogs. In addition, the benzylamide function in compound 5 should be replaced by a phenylurea moiety to gain better cytotoxicity while retaining and improving the selectivity. Thus, maslinic acid derived N-[2 beta,3 beta-di-O-acetyl-17 beta-amino-28-norolean-12-en-17-yliphenylurea (45) gave best results showing EC50 = 0.9 mu M (for A2780 ovarian cancer cells) with EC50 > 120 mu M for fibroblasts (NIH 3T3) and triggered apoptosis while caspase-3 was not activated by this compound. (C) 2016 Elsevier Masson SAS. All rights reserved.