3,11-dioxo-olean-12-en-28-oic acid

• 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-olean-12-en-28-oic acid
• 英文别名: 3,11-dioxoolean-12-en-28-oic acid；12-en-3,11-dioxo-oleanolic acid；(4aS,6aR,6aS,6bR,8aR,12aS,14bS)-2,2,6a,6b,9,9,12a-heptamethyl-10,13-dioxo-1,3,4,5,6,6a,7,8,8a,11,12,14b-dodecahydropicene-4a-carboxylic acid
• 化学式: C₃₀H₄₄O₄
• 分子量: 468.677
• InChiKey: VDDPQVQCXWFZJM-WTRJLLKISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  34
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  71.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,11-dioxo-olean-12-en-28-oic acid 在 lithium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以7%的产率得到4-hydroxy-3,4-seco-11-oxo-olean-12-en-28-oic acid 3,4 lactone
  参考文献：
  名称：

  Design, synthesis and biological evaluation of seco-A-pentacyclic triterpenoids-3,4-lactone as potent non-nucleoside HBV inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2018.03.076
• 作为产物：
  描述：

  3-氧代-12-烯-28-齐墩果酸 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 以11%的产率得到3,11-dioxo-olean-12-en-28-oic acid
  参考文献：
  名称：

  Design, synthesis and biological evaluation of seco-A-pentacyclic triterpenoids-3,4-lactone as potent non-nucleoside HBV inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2018.03.076

文献信息

• Gastroprotective and ulcer-healing activity of oleanolic acid derivatives: In vitro–in vivo relationships
  作者：Marianela Sánchez、Cristina Theoduloz、Guillermo Schmeda-Hirschmann、Iván Razmilic、Tania Yáñez、Jaime A. Rodríguez

  DOI：10.1016/j.lfs.2006.03.044

  日期：2006.8

  The triterpene oleanolic acid 1 and its semisynthetic derivatives 2-7 were assessed for gastroprotective and ulcer-healing effect using human epithelial gastric cells (AGS) and human lung fibroblasts (MRC-5). The ability of the compounds to protect the AGS cells against the damage induced by sodium taurocholate (NaT), to stimulate the cellular reduced glutathione (GSH) and prostaglandin E-2 content, to enhance AGS and MRC-5 cell proliferation and to scavenge superoxide anion in vitro was studied. The cytotoxicity of the compounds was assessed towards MRC-5 and AGS cells. In addition, the gastroprotective activity of the compounds was assessed in vivo using the HCl/EtOH-induced ulcer model in mice. All the assayed compounds displayed a significant reduction of AGS cells damage after incubation with NaT. None of the studied compounds was active as a superoxide anion scavenger nor stimulated the GSH content in AGS, cell cultures. Compounds 1, 2, 4 and 6 were able to increase the prostaglandin content in AGS cell cultures. Concerning the proliferation assays, a significant stimulating effect was observed for compounds 3 and 7 on AGS cells and for 1 and 7 on MRC-5 fibroblasts. Regarding cytotoxicity, derivatives 2, 4, 6 and 7 were less toxic than the parent compound oleanolic acid. Our results strongly support the predictive capacity of the in vitro assessment of gastroprotective activity allowing the reduction of experimental animals. (c) 2006 Elsevier Inc. All rights reserved.
• Practical Application of Oxidation Using a Novel Na₂WO₄−H₂O₂ System under Neutral Conditions for Scale-Up Manufacturing of 12α-Hydroxy-3-oxooleanano-28,13-lactone: Key Intermediate of Endothelin A Receptor Antagonist S-0139
  作者：Takemasa Hida、Yuuki Fukui、Kyozo Kawata、Mikio Kabaki、Toshiaki Masui、Masataka Fumoto、Hideo Nogusa

  DOI：10.1021/op900265h

  日期：2010.1.15

  Novel alcohol oxidation using a Na2WO4-H2O2 System was applied to manufacture 12 alpha-hydroxy-3-oxooleanano-28,13-lactone which is it key intermediate of S-0139. Oxidation of the hydroxyl group of oleanolic acid was optimized based oil the design of experiment (DoE) approach. Statistical analysis was used to maximize the yield of the corresponding ketone and minimize the generation of byproducts. The safety evaluation of this oxidation was also conducted in detail, and pilot manufacturing was achieved.
• Sweet Gum Fruit Extract as a Therapeutic Agent
  申请人：Liu Zhijun

  公开号：US20150110862A1

  公开（公告）日：2015-04-23

  Sweet gum ( Liquidambar styraciflua L., family Hamamelidaceae) fruit extract was discovered to possess potent activities against multiple targets of the PI3K (phosphatidylinositide 3-kinase) pathway, especially the PI3K/Akt and mTOR pathways. At a very low concentration of 1.85 μg/ml (IC50), sweet gun extract showed the ability of simultaneously blocking the pathways of PI3K/Akt (upstream), mTOR (mammalian target of rapamycin) (downstream), as well as its downstream protein products S6K and S6. It was also able to block 5-HETE, a lipoxygenase product that contributes to inflammation and activation of PI3K/Akt. The sweet gum fruit extract was prepared with 50% methanol (47:1; raw to extract) and concentrated to an organic fraction (210:1 raw to extract) referred as LIS-100 via reverse-phase column chromatography using a bioassay directed fractionation approach. The extract is a new targeted therapeutic agent for numerous disorders known to be treated by mTOR inhibitors, including cancer, diabetes, obesity, and inflammation.
• 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.