methyl glycyrrhetate hemisuccinate | 17956-20-6

• 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: methyl glycyrrhetate hemisuccinate
• 英文别名: methyl 3β-O-carboxypropionyl-11-oxoolean-12-ene-30-oate；Methyl 3-O-(β-carboxypropionyl)-18β-glycyrrhetat；18β-glycyrrhetinic acid succinic anhydride ester；4-([(3β)-30-methoxy-11,30-dioxoolean-12-en-3-yl]oxy)-4-oxobutanoic acid；glycyrrhetinic acid methyl ester 3-O-hemisuccinate ester；4-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-methoxycarbonyl-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-4-oxobutanoic acid
• CAS: 17956-20-6
• 化学式: C₃₅H₅₂O₇
• 分子量: 584.794
• InChiKey: OJLLSBNNLNUCKE-BMJPTYCDSA-N

物化性质

• 熔点：
  265-267 °C
• 沸点：
  657.8±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)：
  6.8
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl glycyrrhetate hemisuccinate 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 、 苯 为溶剂， 生成
  参考文献：
  名称：

  Synthesis of Triterpene Derivatives of D-Glucosamine - Modified Analogs of Glycyrrhizic Acid

  摘要：

  合成了含有 18α- 和 18β- 甘草亭酸琥珀酸盐的三萜 D-氨基葡萄糖酰胺。

  DOI：

  10.1007/s10600-005-0061-7
• 作为产物：
  描述：

  甘草次酸 在 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 methyl glycyrrhetate hemisuccinate
  参考文献：
  名称：

  设计，合成和生物功能评价新型五环三萜带有O- [4-（1-哌嗪基）-4-氧代-丁酰基部分作为抗增殖剂。

  摘要：

  合成了一系列带有O- [4-（1-哌嗪基）-4-氧代-丁酰基部分的五环三萜衍生物，并研究了它们潜在的抗增殖活性。五环三萜类化合物的衍生物是通过四步或六步合成程序合成的。使用Cell Counting Kit-8方法评估活性研究，并对A549细胞，MCF-7细胞和Hela细胞进行Western印迹分析。化合物3-O- [4-（1-哌嗪基）-4-氧代-丁酰基] olean-12-ene-28-oate（OA-4）和化合物2-O- [4-（1-哌嗪基）-发现4-氧代-丁酰基] -3，23-二羟基urs-12-烯-28-油酸酯（AA-5）是有前途的抗增殖剂。这些化合物显示出进一步优化作为抗肿瘤药物的潜力。

  DOI：

  10.1016/j.bmcl.2015.08.076

文献信息

• Synthesis, Characterization and In Vitro Evaluation of Self-Assembled poly(ethylene glycol)-glycyrrhetinic Acid Conjugates
  作者：Gu He、Zhiyao He、Xi Zheng、Junmin Li、Chi Liu、Xiangrong Song、Liang Ouyang、Fengbo Wu

  DOI：10.2174/157017812800167448

  日期：2012.3.1

  Glycyrrhetinic acid (GA) is a commonly used drug for the chemotherapy of Chronic Hepatitis B, allergic dermatitis, inflammation, etc. But some problems such as poor water-solubility, low bioavailability and short plasma halflife, have limited its use. In the present study, PEGylation derivatives of GA derivatives were synthesized and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, etc. The PEG-GA conjugates having a critical micelle concentration of 0.081-0.73 mg/mL were used to form nano-sized micelles, with mean diameters of 120.86 ± 31.74 nm. The physico-chemical properties of the PEG – GA conjugate were evaluated including stability, cellular toxicity, and drug release profile. All the conjugates synthesized showed good stabilities in acidic and neutral solutions, while the stability in alkaline solution and the enzymatic hydrolysis rate, were significantly affected by the linkage between the GA and PEG chain. The results demonstrate that, by PEGylation of GA derivatives, the greatly increased water solubility and desirable self-assembly abilities of PEG-GA were obtained. The novel conjugates have potential medical applications for intravenously delivery of insoluble drug delivery.

  甘草次酸(GA)是一种常用于慢性乙型肝炎、过敏性皮炎、炎症等化疗的药物。然而，其水溶性差、生物利用度低和血浆半衰期短等问题限制了其应用。在本研究中，GA的PEG化衍生物通过FTIR、NMR、透射电子显微镜、粒径分析等方法进行了合成和表征。PEG-GA共轭物具有0.081-0.73 mg/mL的临界胶束浓度，用于形成纳米尺寸的胶束，平均直径为120.86 ± 31.74 nm。评估了PEG-GA共轭物的物理化学性质，包括稳定性、细胞毒性和药物释放曲线。所有合成的共轭物在酸性和中性溶液中均显示出良好的稳定性，而在碱性溶液中的稳定性和酶解速率则显著受到GA与PEG链之间连接的影响。结果表明，通过PEG化GA衍生物，获得了显著增加的水溶性和理想的自我组装能力。这种新型共轭物具有通过静脉输注不可溶药物的潜在医疗应用。
• The preparation of some derivatives of glycyrrhetic acid and oleanolic acid
  作者：P D G DEAN、T G HALSALL、M W WHITEHOUSE

  DOI：10.1111/j.2042-7158.1967.tb08011.x

  日期：2011.4.12

  Some new derivatives of glycyrrhetic acid and oleanolic acid were prepared and characterized. Various combinations of the modified and normal functional groups were synthesized as required for a separate study of the uncoupling activities of glycyrrhetic acid and oleanolic acid. The hydroxyl functions of these two acids were modified to β-carboxypropionyl, acetyl and β-methoxycarbonylpropionyl esters. The carboxyl function of glycyrrhetic acid was converted to amide, p-amidobenzoic acid, o-amidobenzoic acid and the glycine conjugate of the acid. 11-Deoxy (glycyrrhetic acid) and 9,11-dehydro-11-deoxo (from both acids) analogues were prepared. 11-Oxo analogues of oleanolic acid were synthesized as well as the methyl esters.

  摘要：制备和表征了一些甘草酸和齐墩果酸的新衍生物。根据需要合成了修改和正常官能团的各种组合，以便对甘草酸和齐墩果酸的解耦活性进行单独研究。这两种酸的羟基功能被修改为β-羧丙酰基、乙酰基和β-甲氧羰基丙酰酯。甘草酸的羧基功能转化为酰胺、对-氨基苯甲酸、邻-氨基苯甲酸和该酸的甘氨酸结合物。制备了11-去氧（甘草酸）和9,11-脱氢-11-去氧（来自两种酸）的类似物。合成了齐墩果酸的11-酮类似物以及甲酯。
• Synthesis of N-glycoconjugates of glycyrrhetic acid
  作者：S. R. Mustafina、L. A. Baltina、R. M. Kondratenko、L. A. Baltina、F. Z. Galin、G. A. Tolstikov

  DOI：10.1007/s10600-006-0037-2

  日期：2006.1

  New N-glycoconjugates that are analogs of glycyrrhizic acid were synthesized by condensation of α-L-rhamnopyranosylamine and β-D-lactosylamine with acid succinate and phthalate of glycyrrhetic acid methyl ester using N,N′-dicyclohexylcarbodiimide (DCC) or DCC-N-hydroxybenzotriazole.

  通过α-L-鼠李糖胺和β-D-乳糖胺与琥珀酸和甘草酸甲酯的邻苯二甲酸盐的缩合，使用N,N′-二环己基碳二亚胺（DCC）或DCC-N-羟基苯并三唑，合成了甘草酸类似物的新型N-糖苷。
• Dual-Ligand-Functionalized Liposomes Based on Glycyrrhetinic Acid and cRGD for Hepatocellular Carcinoma Targeting and Therapy
  作者：Mingxing Qiu、Jiong Wang、Jiaojiao Bai、Xiaoxu Li、Cuiqing Tian、Zhi Liu、Chaoran Zheng、Andrew R. Clark、Xinwei Cheng、Xiaoyan Liao、Song Wu、Robert J. Lee、Xiaoju Zhou

  DOI：10.1021/acs.molpharmaceut.2c00842

  日期：——

  Hepatocellular carcinoma (HCC) is one of the most common cancers, with high mortality. Chemotherapy is one of the main treatment options for HCC. However, the high toxicity and poor specificity of chemotherapeutic drugs have limited their clinical application. In this study, dual-ligand liposomes modified with glycyrrhetinic acid (GA) and cyclic arginine–glycine–aspartic acid (cRGD) (GA/cRGD-LP) were

  肝细胞癌（HCC）是最常见的癌症之一，死亡率很高。化疗是 HCC 的主要治疗选择之一。然而，化疗药物的高毒性和特异性差限制了其临床应用。在这项研究中，设计了用甘草次酸 (GA) 和环状精氨酸-甘氨酸-天冬氨酸 (cRGD) (GA/cRGD-LP) 修饰的双配体脂质体，分别靶向 GA 受体和 αvβ3 整合素。目的是开发一种高选择性的靶向药物递送系统，并通过靶向肝肿瘤细胞和脉管系统进一步提高药物的抗肿瘤效率。通过偶联二油酰磷脂酰乙醇胺 (DOPE) 与甲基甘草次酸 (mGA) 合成了一种新型脂质偶联物 (mGA-DOPE)，并确定了其结构。通过体外细胞摄取和体外成像评估 GA/cRGD-LP 的靶向效率。制备了 GA 和 cRGD 修饰的阿霉素负载脂质体 (GA/cRGD-LP-DOX)，并评估了它们在 HepG2 中的细胞毒性和抗肿瘤活性。结果表明，GA/cRGD-LP-DOX的平均粒径为114±4
• Development of glycyrrhetinic acid-modified stealth cationic liposomes for gene delivery
  作者：Zhi Yao He、Xi Zheng、Xiao Hua Wu、Xiang Rong Song、Gu He、Wen Fang Wu、Shui Yu、Sheng Jun Mao、Yu Quan Wei

  DOI：10.1016/j.ijpharm.2010.06.029

  日期：2010.9

  The glycyrrhetinic acid-modified stealth cationic liposomes (GA-PEG-CLs) loaded with pDNA (GA-PEG-CLPs) were developed and found to transfect human hepatocellular carcinoma cell line HepG2 with high efficiency. GA-PEG-CLs were comprised of DOTAP, cholesterol (Chol) and glycyrrhetinic acid-polyethyleneglycol-cholesterol conjugate (GA-PEG-Chol). Agarose gel electrophoresis revealed that 5% GA-PEG-CLs constituted by DOTAP/Chol/GA-PEG-Chol at molar ratio of 50:45:5 could completely entrap pDNA at a lower liposomes/pDNA weight ratios of 4:1 (N/P ratio: 1.14). Compared to ordinary cationic liposomes (CLs), steric cationic liposomes (PEG-CLs) and 1% GA-PEG-CLs made from DOTAP/Chol/MPEG2000-Chol/GA-PEG-Chol at molar ratio of 50:45:4:1,5% GA-PEG-CLs were found to possess the highest transfection efficiency as gene vectors in serum-free or serum-containing medium in PKC alpha. over-expressed HepG2 cells but no significance difference in human embryonic kidney cell line HEK 293. Additionally, 5% GA-PEG-CLs have the lowest cytotoxicity on human normal hepatocyte cell line L02. The competitive inhibition experiments mediated by GA were carried out in HepG2 cells, which demonstrated that GA-PEG-CLs could deliver selectively pDNA to hepatoma cells by the targeting moiety GA. In conclusion, GA-PEG-CLs containing 5% GA-PEG-Chol might be one of the most potential gene vectors as hepatoma targeting therapy. (C) 2010 Elsevier BM. All rights reserved.