3-β-butyryloxy-ursane-12-en-28-carboxylic acid | 86166-10-1

• 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-β-butyryloxy-ursane-12-en-28-carboxylic acid
• 英文别名: 3β-butanoylursolic acid；(1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-butanoyloxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid
• CAS: 86166-10-1
• 化学式: C₃₄H₅₄O₄
• 分子量: 526.8
• InChiKey: SSQWHYVWFFGUJE-QXQWIYNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-β-butyryloxy-ursane-12-en-28-carboxylic acid 在 草酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 (3S,4aR,6aR,6bS,8aS,11R,12S,12aS,14aR,14bR)-8a-(chlorocarbonyl)-4,4,6a,6b,11,12,14b-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydropicen-3-yl butyrate
  参考文献：
  名称：

  Synthesis and in vitro Cytotoxicity of Novel Ursolic Acid Derivatives

  摘要：

  为了提高潜在的保肝和抗肿瘤活性，研究人员设计并合成了八种新型熊果酸（UA）衍生物，并对 UA 的 C-3、C-11 和 C-28 位置进行了取代。通过红外光谱、质谱和 1H-NMR 以及元素分析确认了它们的结构。它们对各种癌细胞株（HeLa、SKOV3 和 BGC-823）的体外细胞毒性通过标准的 MTT 试验进行了评估。其中，化合物 13 比熊果酸表现出更强的细胞毒性。

  DOI：

  10.3390/molecules15064033
• 作为产物：
  描述：

  熊果酸 、 丁酸 在 4-二甲氨基吡啶 、 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 12.0h， 以78%的产率得到3-β-butyryloxy-ursane-12-en-28-carboxylic acid
  参考文献：
  名称：

  Ursolic acid derivatives as bone anabolic agents targeted to tryptophan hydroxylase 1 (Tph-1)

  摘要：

  Tryptophan hydroxylase 1 (Tph-1) initiates the biosynthesis of peripheral serotonin. As peripheral serotonin suppresses bone formation, inhibitor of Tph-1 provides a useful tool to discover anabolic agents for osteoporosis. In the present study, series of ursolic acid (UA) derivatives were synthesized, and their inhibitory activity on serotonin biosynthesis and cytotoxicity were evaluated. Among the derivatives, 8d with potent inhibitory activity on serotonin was applied for further research. The data revealed that 8d significantly inhibited protein and mRNA expressions of Tph-1, and an SPR study indicated that 8d directly interacted to Tph-1 with a binding affinity of KD=15.09μM. Oral administration of 8d significantly prevented bone loss via suppressing serotonin biosynthesis without estrogenic side-effects in ovariectomized (OVX) rats.

  DOI：

  10.1016/j.ejps.2015.04.021

文献信息

• Semisynthesis, cytotoxicity, antimalarial evaluation and structure-activity relationship of two series of triterpene derivatives
  作者：Simone Tasca Cargnin、Andressa Finkler Staudt、Patrícia Medeiros、Daniel de Medeiros Sol Sol、Ana Paula de Azevedo dos Santos、Fernando Berton Zanchi、Grace Gosmann、Antonio Puyet、Carolina Bioni Garcia Teles、Simone Baggio Gnoatto

  DOI：10.1016/j.bmcl.2017.12.060

  日期：2018.2

  semisynthesis of two series of ursolic and betulinic acid derivatives through designed by modifications at the C-3 and C-28 positions and demonstrate their antimalarial activity against chloroquine-resistant P. falciparum (W2 strain). Structural modifications at C-3 were more advantageous to antimalarial activity than simultaneous modifications at C-3 and C-28 positions. The ester derivative, 3β-butanoyl betulinic

  在这份报告中，我们描述了通过在C-3和C-28位置进行修饰设计而设计的两个系列的熊草酸和桦木酸衍生物的半合成，并证明了它们对耐氯喹的恶性疟原虫（W2株）具有抗疟活性。与在C-3和C-28位置同时进行修饰相比，在C-3处进行结构修饰更有利于抗疟疾活性。酯衍生物3β-丁酰桦木酸（7b）是活性最高的化合物（IC 50  = 3.4 µM），对VERO和HepG2细胞均无细胞毒性（CC 50  > 400 µM），显示出对寄生虫的选择性（选择性）索引> 117.47）。与青蒿素合用，化合物7b表现出加和效应（CI = 1.14）。对接分析显示7b与疟原虫蛋白酶PfSUB1可能发生相互作用，最佳结合亲和力为-7.02 kcal / mol，地衣芽孢杆菌枯草杆菌蛋白酶A蛋白酶活性测定（IC 50  = 93 µM）和观察到的环形式积累以及滋养体在体外的出现延迟表明，疟原虫上3β-丁酰基桦木酸的主要靶标
• 乌苏酸化学修饰物及其制备方法和应用
  申请人：广东工业大学

  公开号：CN104045678B

  公开（公告）日：2016-03-02

  本发明公开了一种乌苏酸化学修饰物及其制备方法和应用，该乌苏酸化学修饰物结构式为下式：其中：R1为酰基；R2为胺基：制备方法，乌苏酸和酸酐在催化剂条件下反应得到3β‐酰氧基‐乌苏烷型‐12‐烯‐28‐羧酸类化合物2～5；化合物2～5利用草酰氯在冰浴条件下酰化，得到3‐乙酰氧基‐乌苏烷型‐12烯‐28‐酰氯，再在缚酸剂条件下，与苯胺反应得N‐(3β‐乙酰氧基‐乌苏烷型‐12‐烯‐28‐酰)‐胺类化合物；该化合物具有抑制酶活性的作用，可应用在制备预防、控制或治疗血糖水平升高糖尿病或肥胖症的药品、饮品、食品和保健品中；属于药物合成技术领域。
• Synthesis and evaluation of the HIF-1α inhibitory activities of novel ursolic acid tetrazole derivatives
  作者：Lin-Hao Zhang、Zhi-Hong Zhang、Ming-Yue Li、Zhi-Yu Wei、Xue-Jun Jin、Hu-Ri Piao

  DOI：10.1016/j.bmcl.2019.04.028

  日期：2019.6

  metastasis. Therefore, the inhibition of this pathway is an important therapeutic target for the treatment of various types of cancers. Here, we designed and synthesized 31 ursolic acid (UA) derivatives containing a tetrazole moiety and evaluated them for their potential anti-tumor activities as HIF-1α transcriptional inhibitors. Of these, compound 14d (IC50 0.8 ± 0.2 µM) displayed the most potent activity

  缺氧诱导因子-1α（HIF-1α）通路与肿瘤血管生成，生长和转移有关。因此，抑制该途径是治疗各种类型癌症的重要治疗靶标。在这里，我们设计和合成了31个含有四唑部分的熊果酸（UA）衍生物，并对其作为HIF-1α转录抑制剂的潜在抗肿瘤活性进行了评估。其中，化合物14d（IC50 0.8±0.2 µM）表现出最强的活性，化合物14a（IC50 4.7±0.2 µM）表现出最有前途的生物学特性。对这些化合物与HIF-1α的构效关系的分析表明，位于UA衍生物C-28处的四唑基的存在对其抑制活性至关重要。
• In vitro and in vivo evaluation of the antidiabetic activity of ursolic acid derivatives
  作者：Pan-Pan Wu、Kun Zhang、Yu-Jing Lu、Ping He、Su-Qing Zhao

  DOI：10.1016/j.ejmech.2014.04.073

  日期：2014.6

  In this study, a series of ursolic acid derivatives were synthesized, and their structures were confirmed. The activity of the synthesized compounds against α-glucosidase was determined in vitro. The results suggested that all compounds have significant inhibitory activity, especially compounds 3-5 and 8, the IC50 values of which were 2.66 ± 0.84, 1.01 ± 0.44, 3.26 ± 0.22, and 3.24 ± 0.21 μM. These compounds were more potent than acarbose (positive control) against α-glucosidase. Kinetic studies were performed to determine the mechanism of inhibition by compounds 3-5 and 8. The kinetic inhibition studies indicated that compound 3 was a non-competitive inhibitor, and the inhibition constant Ki was calculated to be 2.67 ± 0.19 μM. Moreover, the kinetic inhibition studies of compounds 4, 5 and 8 demonstrated that they were mixed-type inhibitors. Furthermore, the actual pharmacological potentials of synthesized compounds 3 and 4 were demonstrated by the reduction of postprandial blood glucose levels in normal Kunming mice. The hypoglycemic effects of these compounds were more evident 30 and 60 min after maltose ingestion (P < 0.05), which was similar to the effect displayed by the positive control, acarbose.
• Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species
  作者：Huang-Yao Tu、A-Mei Huang、Bai-Luh Wei、Kim-Hong Gan、Tzyh-Chyuan Hour、Shyh-Chyun Yang、Yeong-Shiau Pu、Chun-Nan Lin

  DOI：10.1016/j.bmc.2009.08.046

  日期：2009.10

  Twenty-three ursolic acid (1) derivatives 2-24 including nine new 1 derivatives 5, 7-11, 20-22 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell line). Compounds 5 and 17 with an isopropyl ester moiety at C-17-COOH and a succinyl moiety at C-3-OH showed potent inhibitory effect on growth of NTUB1 cells. Compounds 23 and 24 with seco-structures prepared from 1 also showed the increase of the cytotoxicity against NTUB1 cells. Exposure of NTUB1 to 5 (40 mu M) and 23 (20 and 50 mu M) for 24 h significantly increased the production of reactive oxygen species (ROS) while exposure of NTUB1 to 5 (20 and 40 mu M) and 23 (20 and 50 mu M) for 48 h also significantly increased the production of ROS while exposure of cells to 17 did not increase the amount of ROS. Flow cytometric analysis exhibited that treatment of NTUB1 with 5 or 17 or 23 led to the cell cycle arrest accompanied by an increase in apoptotic cell death after 24 or 48 h. These data suggest that the presentation of G1 phase arrest and apoptosis in 5- and 23-treated NTUB1 for 24 h mediated through increased amount of ROS in cells exposed with 5 and 23, respectively, while the presence of G2/M arrest before accumulation of cells in sub-G1 phase in 5-treated cells for 48 h also due to increased amount of ROS in cells exposed with 5. The inhibition of tubulin polymerization and cell cycle arrest at G2/M following by apoptosis presented in the cell cycle of 23 also mediates through the increase amount of ROS induced by treating NTUB1 with 23 for 48 h. (C) 2009 Elsevier Ltd. All rights reserved.