3,11-dioxo-18β-oleanane-12-ene-30-carboxylic acid benzyl ester | 1321990-56-0

• 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: 3,11-dioxo-18β-oleanane-12-ene-30-carboxylic acid benzyl ester
• 英文别名: benzyl 3,11-dioxo-18β-oleana-12-ene-30-oate；benzyl 3,11-dioxoolean-12-en-30-oate；benzyl (2S,4aS,6aR,6aS,6bR,8aR,12aS,14bR)-2,4a,6a,6b,9,9,12a-heptamethyl-10,13-dioxo-1,3,4,5,6,6a,7,8,8a,11,12,14b-dodecahydropicene-2-carboxylate
• CAS: 1321990-56-0
• 化学式: C₃₇H₅₀O₄
• 分子量: 558.802
• InChiKey: KURRMEBPVBFSDN-DBPANWPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  41
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,11-dioxo-18β-oleanane-12-ene-30-carboxylic acid benzyl ester 在 对甲苯磺酸 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 生成 3,4-seco-11-oxo-18β-olean-4(23),12-diene-3,30-dioic acid 30-benzyl ester
  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 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 9.5h， 生成 3,11-dioxo-18β-oleanane-12-ene-30-carboxylic acid benzyl ester
  参考文献：
  名称：

  新型 18β-甘草次酸衍生物作为二合一药物，具有强大的抗菌和抗炎活性

  摘要：

  18 β-甘草次酸 (GA) 是一种众所周知的齐墩果烷型三萜的天然化合物，被发现具有抗菌和抗炎特性。尽管如此，其相对较低的生物活性限制了其在药物应用中的潜力。为了最大限度地利用这种天然草药化合物作为抗菌和抗炎剂，对 GA 进行合理修饰以增强其低毒药理活性并了解作用机制至关重要。我们在此报道了一系列新的 GA 衍生物的设计和合成。这些新化合物的抗菌活性通过抑菌圈试验和最低抑菌浓度（MIC）测定来评估。此外，通过 LPS 诱导的 BV2 细胞炎症模型和 12-O-十四烷酰佛波醇 13-乙酸 (TPA) 诱导的耳部炎症小鼠模型。发现在 GA 的 2 位被二取代的苯基官能化的衍生物通常对革兰氏阳性细菌表现出高抗菌活性（MIC 低至 2.5 μM）和有效的抗炎作用（抑制 NO 产生55%，与地塞米松相当）。体外和体内结果还表明，GA-O-02和GA-O-06通过下调 NO、促炎细胞因子和趋化因子（I

  DOI：

  10.1016/j.bioorg.2022.105714

文献信息

• Synthesis and biological activity of glycyrrhetinic acid derivatives as antitumor agents
  作者：Fei Zhou、Gao-Rong Wu、De-Sheng Cai、Bing Xu、Meng-Meng Yan、Tao Ma、Wen-Bo Guo、Wen-Xi Zhang、Xue-Mei Huang、Xiao-hui Jia、Yu-Qin Yang、Feng Gao、Peng-Long Wang、Hai-Min Lei

  DOI：10.1016/j.ejmech.2019.06.029

  日期：2019.9

  all the de-protected (without Boc group) derivatives showed much stronger cytotoxic activity than GA, and surprisingly enough, all the GN series of the compounds were more potent than GO series against various tumor cells. Among them, the compound 26 (amide linkages in C-3 position) exhibited stronger antitumor activity against A549 cell line (IC50 = 2.109 ± 0.11 μM) than the positive drug cisplatin (IC50 = 9

  甘草次酸（GA）一直是抗癌的先导化合物，并吸引了世界各地的许多科学家。然而，其抗肿瘤活性还不够强。为提高GA的细胞毒性并探讨键合方式对抗肿瘤活性的影响，GA-OH系列（GO，C-3位的酯）和GA-NH 2系列（GN，C-3位的酰胺键）包括32种化合物已经被设计和合成了。对所有化合物进行了体外筛选对A549，HepG2，MCF-7，Hela和MDCK细胞系的细胞毒性。结果，所有去保护的（没有Boc基团）衍生物都显示出比GA强得多的细胞毒活性，而且令人惊讶的是，所有GN系列化合物对各种肿瘤细胞的功效都比GO系列更强。其中，化合物26（位于C-3位置的酰胺键）对A549细胞系（IC 50  = 2.109±0.11μM ）表现出比阳性药物顺铂（IC 50  = 9.001±0.37μM）更强的抗肿瘤活性。进一步的研究表明，化合物26可以通过细胞核断裂诱导A549细胞凋亡。凋亡的检测和细胞周期分析
• 18β-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents
  作者：Li-Rong Huang、Xiao-Jiang Hao、Qi-Ji Li、Dao-Ping Wang、Jian-Xin Zhang、Heng Luo、Xiao-Sheng Yang

  DOI：10.1021/acs.jnatprod.5b00641

  日期：2016.4.22

  most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined

  通过在C-20处引入三羟基化的A环和酯部分以化学方式修饰齐墩果烷型三萜18β-甘草次酸（1），以增强其抗菌活性。化合物22，23，25，28，29，31，和32显示出更有效的抑制活性对链霉菌疥比阳性对照，链霉素。此外，最有效的化合物29对枯草芽孢杆菌，金黄色葡萄球菌和耐甲氧西林的金黄色葡萄球菌的抑制活性大于阳性对照。活性衍生物的抗菌作用方式包括调节与肽聚糖相关的基因的表达，呼吸代谢和细菌中发现的固有毒力因子，这是通过定量实时逆转录酶PCR分析确定的。
• 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。
• 2-取代-18β-甘草次酸衍生物及其应用
  申请人：沈阳药科大学

  公开号：CN108640965B

  公开（公告）日：2021-11-05

  本发明属于医药技术领域，具体涉及18β‑甘草次酸衍生物及其旋光异构体和药学上可接受的盐，该衍生物的制备方法，以该衍生物为活性成分的药物组合物，用于制备治疗和/或预防各种癌症的药物中的用途。所述的通式I所示的衍生物，及其旋光异构体和药学上可接受的盐结构如下：其中，各变量如权利要求和说明书所述。
• Synthesis and antitumor effects of novel 18β-glycyrrhetinic acid derivatives featuring an exocyclic α,β-unsaturated carbonyl moiety in ring A
  作者：Min Huang、Ping Gong、Yuetong Wang、Xiaorui Xie、Zhuangshi Ma、Qihao Xu、Dan Liu、Yongkui Jing、Linxiang Zhao

  DOI：10.1016/j.bioorg.2020.104187

  日期：2020.10

  18β-glycyrrhetinic acid (GA) derivatives featuring an exocyclic α,β-unsaturated carbonyl moiety in ring A were synthesized and evaluated for their antitumor activities. Compounds 5c and 5l showed stronger cytotoxicity than other compounds and reported GA analogue CDODA-Me (methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate). 5c and 5l induced apoptosis in cancer cells accompanying with c-Flip reduction and

  一系列新颖18的β设有一个环外β-甘草酸（GA）衍生的α，β不饱和羰基在环A的合成和评价其抗肿瘤活性部分。化合物5C和5升表现出比其它化合物更强的细胞毒性，并报告GA类似物CDODA-Me（甲基2-氰基-3,11-二氧代18 β -olean -1,12-二烯30 -酸酯）。5c和5l诱导癌细胞凋亡，并伴有c-Flip减少和Noxa诱导，与HDAC3表达降低和H3乙酰化增加有关。5l在微粒体和血浆中的稳定性优于5c和CDODA-Me，5l还显示出良好的药代动力学特征，并抑制了小鼠的肿瘤生长。化合物51表示具有改善的抗肿瘤活性的新型GA衍生物。