2-hydroxy-3-oxo-oleana-1,12-dien-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: 2-hydroxy-3-oxo-oleana-1,12-dien-28-oic acid
• 英文别名: 2-hydroxy-3-oxooleana-1,12-dien-28-oic acid；2-hydroxy-3-oxo-2,12-oleandien-28-oic acid；2-hydroxy-3-oxoolean-1,12-dien-28-oic acid；Pancreatic lipase/Carboxylesterase 1-IN-1；(4aS,6aR,6aS,6bR,8aR,12aR,14bS)-11-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-10-oxo-3,4,5,6,6a,7,8,8a,13,14b-decahydro-1H-picene-4a-carboxylic acid
• 化学式: C₃₀H₄₄O₄
• 分子量: 468.677
• InChiKey: OQLDDXDMTOPTDO-QRARIYCASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  34
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-hydroxy-3-oxo-oleana-1,12-dien-28-oic acid 在 双氧水 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.67h， 以40.5%的产率得到2,3-seco-olean-12-en-2,3,28-trioic acid
  参考文献：
  名称：

  Synthesis and evaluation of A-seco type triterpenoids for anti-HIV-1protease activity

  摘要：

  2,3-Seco-dioic acids derived from four different triterpene skeletons were prepared and evaluated for their anti-HIV-1 protease activity. Two A-seco derivatives showed potent inhibitory activity against HIV-1 protease (3c and 3e, IC50 5.7 and 3.9 mu M, respectively), while four other derivatives showed moderate to weak inhibition (3a, 3b, 3d and 3f, IC50 15.7-88.1 mu M). The combination of a 2,3-seco-2,3-dioic acid functional group in ring A and a free acid group at C-28 or C-30 significantly enhanced HIV-1 protease inhibitory activity (3a, 3c-3e, IC50 3.9-17.6 mu M). On the other hand, all A-seco derivatives were found to be very weak inhibitors of HCV, renin and trypsin proteases (IC50 > 80 mu M). These findings indicate that A-seco triterpenes with a carboxyl group at C-28 or C-30 are novel and highly selective HIV-1 protease inhibitors. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.05.002
• 作为产物：
  描述：

  山楂酸 在 Jones reagent 作用下， 以 丙酮 为溶剂， 反应 1.0h， 生成 2-hydroxy-3-oxo-oleana-1,12-dien-28-oic acid
  参考文献：
  名称：

  亲电子三萜烯酮：硫醇诱捕和生物活性的比较研究。

  摘要：

  Bardoxolone甲基（1）是三萜氰基丙烯酸酯的典型成员，这是一类新兴的能够与硫醇瞬时共价结合的生物活性化合物。这种异常的“脉冲反应性”特征的机理基础及其生物学翻译的模式尚不清楚。为了提供对这些问题的线索，一系列的Δ 1 -dehydrooleanolates轴承在C-2的吸电子基团（7a中-米）从齐墩果酸制备（图3a），并在与硫醇的反应性和对一系列亲电敏感的转录因子（Nrf2，NF-κB，STAT3）的生物活性方面进行了比较研究。新兴的图片表明，三萜骨架通过空间阻碍显着降低了烯酮体系的反应性，并且只有强亲电和空间上不需要的取代基（如氰化物或羧酸酯基团）才能重新建立迈克尔反应性，尽管这是一种短暂的方式。氰化物基团。通常，观察到在硫醇捕获能力和对硫醇烷基化敏感的生物端点的调节之间的实质分离，突出了形状互补性对三萜类噻吩-迈克尔受体活性的作用。

  DOI：

  10.1021/acs.jnatprod.7b00271

文献信息

• Novel Synthetic Oleanane and Ursane Triterpenoids with Various Enone Functionalities in Ring A as Inhibitors of Nitric Oxide Production in Mouse Macrophages
  作者：Tadashi Honda、Gordon W. Gribble、Nanjoo Suh、Heather J. Finlay、BarbieAnn V. Rounds、Lothar Bore、Frank G. Favaloro,、Yongping Wang、Michael B. Sporn

  DOI：10.1021/jm000008j

  日期：2000.5.1

  We initially randomly synthesized about 60 oleanane and ursane triterpenoids as potential anti-inflammatory and cancer chemopreventive agents. Preliminary screening of these derivatives for inhibition of production of nitric oxide induced by interferon-gamma in mouse macrophages revealed that 3-oxooleana-1, 12-dien-28-oic acid (B-15) showed significant activity (IC(50) = 5.6 microM). On the basis of

  最初，我们随机合成了约60种齐墩果烷和乌桑烷三萜作为潜在的抗炎药和癌症化学预防剂。初步筛选抑制小鼠巨噬细胞中干扰素-γ诱导的一氧化氮生成的这些衍生物，发现3-氧代油酸酯-1、12-二烯-28-酸（B-15）显示出显着的活性（IC（50）= 5.6微米）。基于B-15的结构，设计并合成了19个具有1-en-3-one官能团的，在A环的C-2处具有取代基的新颖的1-和urs-12-烯三萜。其中，在C-2处具有羧基，甲氧基羰基和腈基的3-氧代油酸酯-1,12-二烯衍生物比铅化合物B-15具有更高的活性。特别是，2-羧基-3-氧代油酸-1，12-二烯-28-油酸（3）具有最高的活性（IC（50）= 0。07 microM）中的三萜类化合物。3的效力类似于氢化可的松（IC（50）= 0.01 microM），尽管3并不通过糖皮质激素受体起作用。还讨论了这些新颖的合成三萜类化合物的有趣的构效关系。
• Convenient and chromatography-free partial syntheses of maslinic acid and augustic acid
  作者：Sven Sommerwerk、René Csuk

  DOI：10.1016/j.tetlet.2014.07.074

  日期：2014.9

  A convenient and chromatography-free 4-step synthesis of analytically pure maslinic acid (1, 41.2%) from oleanolic acid has been developed. Slight variations in the final steps gave an excellent yield of isomeric augustic acid (7, 71.9%).

  分析纯的山楂酸（的一种方便和自由色谱- 4步合成1从齐墩果酸，41.2％）已被开发。在最后的步骤的轻微变化，得到异构体augustic酸（的优良产率7，71.9％）。
• Discovery of triterpenoids as potent dual inhibitors of pancreatic lipase and human carboxylesterase 1
  作者：Jing Zhang、Qiu-Sha Pan、Xing-Kai Qian、Xiang-Lu Zhou、Ya-Jie Wang、Rong-Jing He、Le-Tian Wang、Yan-Ran Li、Hong Huo、Cheng-Gong Sun、Lei Sun、Li-Wei Zou、Ling Yang

  DOI：10.1080/14756366.2022.2029855

  日期：2022.12.31

  inhibitors based on PL and hCES1A hold great potential for the development of remedies for treating related metabolic diseases. In this study, a series of natural triterpenoids were collected and the inhibitory effects of these triterpenoids on PL and hCES1A were determined using fluorescence-based biochemical assays. It was found that oleanolic acid (OA) and ursolic acid (UA) have the excellent inhibitory

  摘要 胰脂肪酶（PL）是众所周知的预防和治疗肥胖的关键靶点。人羧酸酯酶1A（hCES1A）已成为治疗高脂血症的重要靶点。因此，基于 PL 和 hCES1A 的强效双靶点抑制剂的发现对于开发治疗相关代谢疾病的药物具有巨大潜力。在这项研究中，收集了一系列天然三萜类化合物，并使用基于荧光的生化测定法确定了这些三萜类化合物对 PL 和 hCES1A 的抑制作用。发现齐墩果酸（OA）和熊果酸（UA）对PL和hCES1A具有优异的抑制作用，对hCES2A具有较高的选择性。随后，合成并评估了许多基于 OA 和 UA 骨架的化合物。41 ) 对于 PL 和 hCES1A 抑制都非常重要，IC 50分别为 0.75 µM 和 0.014 µM。此外，OA 的 2-烯醇和 3-缩酮部分的化合物39对 PL 和 hCES1A 也有很强的抑制作用，IC 50分别为 2.13 µM 和 0.055 µM。此外，化合
• New enone derivatives of oleanolic acid and ursolic acid as inhibitors of nitric oxide production in mouse macrophages
  作者：Tadashi Honda、Heather J. Finlay、Gordon W. Gribble、Nanjoo Suh、Michael B. Sporn

  DOI：10.1016/s0960-894x(97)00279-5

  日期：1997.7

  New derivatives of 3-oxoolean-1-en-28 oic acid and 3-oxours-1-en-28-oic acid were synthesized. Nine of them showed significant inhibitory activity against interferon-gamma-induced nitric oxide production in mouse macrophages when assayed at the 1 mu M level. 3,12-Dioxoolean-1,9-dien-28-oic acid (3) had the highest activity (IC50, 0.9 mu M). (C) 1997 Elsevier Science Ltd.
• Fluorescent Probes for Subcellular Localization during Osteclast Formation
  作者：Jing Wu、Qi Shen、Yue Wang、Dan Zhao、Chen Peng、Jian-Xin Li

  DOI：10.1021/ml500181e

  日期：2014.8.14

  Labeling of a small bioactive molecule with fluorescent probe has been becoming an essential tool in cell biology to reveal the subcellular distribution and the location of a molecular target. QOA-8a is a novel molecule with potent antiosteoporotic effect in vivo. To investigate the molecular mechanism of QOA-8a, novel fluorescence-tagged chemical probes as bioactive as their parent molecule were designed and synthesized. The fluorescent compound 12 showed a more potent inhibitory activity on RANKL-induced osteoclastogenesis at 2 μM compared with that of QOA-8a. Microscopy experiments revealed that almost all of probe 12 accumulated in the fusing region, with little in the osteoclast precursors or the mature osteoclasts during osteoclast formation. The result suggests the location of the binding target of QOA-8a, which might greatly narrow down the search field of the target protein(s).