3,11-dioxo-4-oxa-A-homo-olean-12-en-30-oic acid | 103498-64-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 3,11-dioxo-4-oxa-A-homo-olean-12-en-30-oic acid
• 英文别名: glycyrrhetinic acid lactone；(1R,2S,5S,8S,10R,14R,15S,21R)-1,2,5,8,15,20,20-heptamethyl-13,18-dioxo-19-oxapentacyclo[12.9.0.02,11.05,10.015,21]tricos-11-ene-8-carboxylic acid
• CAS: 103498-64-2
• 化学式: C₃₀H₄₄O₅
• 分子量: 484.676
• InChiKey: BGAWWKJPNCEIOU-LPXJIFNVSA-N

物化性质

• 沸点：
  621.5±55.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  35
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,11-dioxo-4-oxa-A-homo-olean-12-en-30-oic acid 在 4-二甲氨基吡啶 、 对甲苯磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 30-phenylcarbamoyl-11-oxo-18β-3,4-secoolean-4(23),12-dien-3-oic acid
  参考文献：
  名称：

  18β-Glycyrrhetinic acid derivatives induced mitochondrial-mediated apoptosis through reactive oxygen species-mediated p53 activation in NTUB1 cells

  摘要：

  Twenty six 18 beta-glycyrrhetinic acid (GA) (1) derivatives 2-27 including twelve new GA derivatives 10, 11, 13-17, 21-25 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell lines). seco-Compounds 9, 25, and 27 are the most potent compounds of this series, inhibiting cell growth of human NTUB1 cells with an IC50 values of 2.34 +/- 0.28, 4.76 +/- 1.15, and 3.31 +/- 0.61 mu M, respectively. Exposure of NTUB1 to 25 for 24 h significantly increased the production of reactive oxygen species (ROS). Flow cytometric analysis exhibited that treatment of NTUB1 with 25 did not induce cell cycle arrest but accompanied by an increase of apoptotic cell death in a dose-dependant manner after 24 h. Mitochondrial membrane potential (MMP) decreased significantly in a dose-dependant manner when the NTUB1 cells were exposed to 25 for 24 h. Marked collapse of the MMP suggested that dysfunction of the mitochondria may be involved in the oxidative burst and apoptosis induced by 25. Western blot analysis shows that NTUB1 cells treated with 25 increased the level of p-p53 in a dose-dependant manner. Further, NAC treatment prevented p53 phosphorylation stimulated by 25. These results suggested that 25 induced a mitochondrial-mediated apoptosis in NTUB1 cells through activation of p53, which are mainly mediated ROS generated by 25. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.05.054
• 作为产物：
  描述：

  甘草次酸 在 Jones reagent 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 3,11-dioxo-4-oxa-A-homo-olean-12-en-30-oic acid
  参考文献：
  名称：

  新型A环裂解甘草次酸衍生物的合成及其抗增殖活性

  摘要：

  通过A环的打开以及氨基酸的偶联合成了一系列新的甘草次酸衍生物。针对一组九种人类癌细胞系评估了衍生物的抗增殖活性。化合物 17 是最活跃的化合物，对 Jurkat 细胞的 IC50 为 6.1 µM，其效力比甘草次酸强 17 倍，并且对癌细胞系的选择性高出 10 倍。Jurkat 细胞的进一步生物学研究表明，化合物 17 的抗增殖活性是由于细胞周期停滞在 S 期并诱导细胞凋亡。

  DOI：

  10.3390/molecules24162938

文献信息

• DERIVATIVE OF 18beta-GLYCYRRHETINIC ACID APT TO SUPPRESS CANCER CELLS
  申请人：Lin Chun-Nan

  公开号：US20130109752A1

  公开（公告）日：2013-05-02

  The present invention is correlated with a derivative of 18β-glycyrrhetinic acid apt to suppressing cancer cells, which is selected from a group comprising of structure I and structure II: wherein residue R 1 is selected from one of CH 3 and CH 2 C 6 H 5 , residue R 2 is selected from one of COOCH 3 , COOCH 2 CH 3 , COOCH(CH 3 ) 2 , CONHCH 2 CH 3 , CONHCH 2 CH 2 CH 3 , and CONHCH 2 (CH 3 ) 2 , and residue R 3 is selected from one of COOCH 2 CH 3 , COOCH(CH 3 ) 2 , CONHCH 2 CH 3 , CONHCH 2 CH 2 CH 3 , and CONHCH 2 (CH 3 ) 2 .

  本发明涉及与18β-甘草酸衍生物相关，适于抑制癌细胞，所选取自包括结构I和结构II的一组中的一种，其中残基R1选择自CH3和CH2C6H5之一，残基R2选择自COOCH3、COOCH2CH3、COOCH(CH3)2、CONHCH2CH3、CONHCH2CH2CH3和CONHCH2(CH3)2之一，残基R3选择自COOCH2CH3、COOCH(CH3)2、CONHCH2CH3、CONHCH2CH2CH3和CONHCH2(CH3)2之一。
• Synthesis, anti-inflammatory, and antioxidant activities of 18β-glycyrrhetinic acid derivatives as chemical mediators and xanthine oxidase inhibitors
  作者：Dravidum Maitraie、Chi-Feng Hung、Huang-Yao Tu、Ya-Ting Liou、Bai-Luh Wei、Shyh-Chyun Yang、Jih-Pyang Wang、Chun-Nan Lin

  DOI：10.1016/j.bmc.2009.02.025

  日期：2009.4

  Twenty 18 beta-glycyrrhetic acid (18 beta-GA) derivatives 2-21 including 13 new 18 beta-GA derivatives were synthesized and evaluated as anti-inflammatory and antioxidant agents. Compounds 7 and 20 with a 3,4-seco-structure and compound 6 with a lactone moiety showed potent inhibitory effect on superoxide anion generation in rat neutrophils response to fMLP/CB and PMA, respectively. Compound 6 with a lactone moiety revealed stronger inhibitory effect on XO activity than those of compounds 13 and 14 with a 3,4-seco-struture. Compound 14, a 30-isoproylcarbamoyl seco-compound exhibited potent inhibitory effect on NO accumulation and iNOS protein expression while compounds 3, 10, 13, 15, 17, and 21 revealed potent inhibitory effect on tumor necrosis factor-alpha (TNF-alpha) formation in RAW 264.7 cells in response to lipopolysaccharide (LPS). The cleavage of ring A of 3 attenuated the inhibitory effect on TNF-alpha formation in RAW 264.7 cells in response to LPS except for 17. The present results suggested these compounds were potential to be served as anti-inflammatory and antioxidant agents. (c) 2009 Elsevier Ltd. All rights reserved.
• Design, synthesis and biological evaluation of seco-A-pentacyclic triterpenoids-3,4-lactone as potent non-nucleoside HBV inhibitors
  作者：Zhijian Li、Qingxi Min、Haoji Huang、Ruixuan Liu、Yongyan Zhu、Quanhong Zhu

  DOI：10.1016/j.bmcl.2018.03.076

  日期：2018.5

  A series of seco-A-pentacyclic triterpenoids-3,4-lactone were synthesized and the anti-HBV activities were evaluated in vitro. Several compounds inhibited the secretion of HBV antigen and the replication of HBV DNA in micromolar level. Compounds D7 and D10, seco-A-oleanane-3,4-lactone, suppressed the HBeAg secretion with IC50 values of 0.14 mu M and 0.86 mu M respectively, and the inhibitory activities were also confirmed by detecting the fluorescence intensity of FITC-labeled monoclonal mouse HBeAg antibody via flow cytometry. Compounds D7 and D10 as well as B4, ring-A cleaved 3,30-dioic acid, also displayed remarkable inhibition on both HBV DNA replication at the concentration of 25 mu M and HBV cccDNA (covalently closed circularDNA) replication with IC50 values of 33.5 mu M, 32.7 mu M and 12.3 mu M respectively. (C) 2018 Elsevier Ltd. All rights reserved.
• Synthesis and Antiproliferative Activity of Novel A-Ring Cleaved Glycyrrhetinic Acid Derivatives
  作者：Daniela P.S. Alho、Jorge A.R. Salvador、Marta Cascante、Silvia Marin

  DOI：10.3390/molecules24162938

  日期：——

  series of new glycyrrhetinic acid derivatives was synthesized via the opening of its ring A along with the coupling of an amino acid. The antiproliferative activity of the derivatives was evaluated against a panel of nine human cancer cell lines. Compound 17 was the most active compound, with an IC50 of 6.1 µM on Jurkat cells, which is 17-fold more potent than that of glycyrrhetinic acid, and was up

  通过A环的打开以及氨基酸的偶联合成了一系列新的甘草次酸衍生物。针对一组九种人类癌细胞系评估了衍生物的抗增殖活性。化合物 17 是最活跃的化合物，对 Jurkat 细胞的 IC50 为 6.1 µM，其效力比甘草次酸强 17 倍，并且对癌细胞系的选择性高出 10 倍。Jurkat 细胞的进一步生物学研究表明，化合物 17 的抗增殖活性是由于细胞周期停滞在 S 期并诱导细胞凋亡。
• 18β-Glycyrrhetinic acid derivatives induced mitochondrial-mediated apoptosis through reactive oxygen species-mediated p53 activation in NTUB1 cells
  作者：Kai-Wei Lin、A-Mei Huang、Tzyh-Chyuan Hour、Shyh-Chyun Yang、Yeong-Shiau Pu、Chun-Nan Lin

  DOI：10.1016/j.bmc.2011.05.054

  日期：2011.7

  Twenty six 18 beta-glycyrrhetinic acid (GA) (1) derivatives 2-27 including twelve new GA derivatives 10, 11, 13-17, 21-25 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell lines). seco-Compounds 9, 25, and 27 are the most potent compounds of this series, inhibiting cell growth of human NTUB1 cells with an IC50 values of 2.34 +/- 0.28, 4.76 +/- 1.15, and 3.31 +/- 0.61 mu M, respectively. Exposure of NTUB1 to 25 for 24 h significantly increased the production of reactive oxygen species (ROS). Flow cytometric analysis exhibited that treatment of NTUB1 with 25 did not induce cell cycle arrest but accompanied by an increase of apoptotic cell death in a dose-dependant manner after 24 h. Mitochondrial membrane potential (MMP) decreased significantly in a dose-dependant manner when the NTUB1 cells were exposed to 25 for 24 h. Marked collapse of the MMP suggested that dysfunction of the mitochondria may be involved in the oxidative burst and apoptosis induced by 25. Western blot analysis shows that NTUB1 cells treated with 25 increased the level of p-p53 in a dose-dependant manner. Further, NAC treatment prevented p53 phosphorylation stimulated by 25. These results suggested that 25 induced a mitochondrial-mediated apoptosis in NTUB1 cells through activation of p53, which are mainly mediated ROS generated by 25. (C) 2011 Elsevier Ltd. All rights reserved.