3β-[(4-carboxyl)butyryloxy]-urs-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: 3β-[(4-carboxyl)butyryloxy]-urs-12-en-28-oic acid
• 英文别名: 3b-[(3-carboxy)n-butyryloxy]-urs-12-en-28-oic acid；(1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-(4-carboxybutanoyloxy)-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
• 化学式: C₃₅H₅₄O₆
• 分子量: 570.81
• InChiKey: XYSNCRDONRILQT-MQCXLNOWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3β-[(4-carboxyl)butyryloxy]-urs-12-en-28-oic acid 、 三甲基硅烷化重氮甲烷 以 甲醇 、 苯 为溶剂， 以100%的产率得到5-O-[(3S,4aR,6aR,6bS,8aS,11R,12S,12aS,14aR,14bR)-8a-methoxycarbonyl-4,4,6a,6b,11,12,14b-heptamethyl-2,3,4a,5,6,7,8,9,10,11,12,12a,14,14a-tetradecahydro-1H-picen-3-yl] 1-O-methyl pentanedioate
  参考文献：
  名称：

  Inhibitory Effects of Constituents from Cynomorium songaricum and Related Triterpene Derivatives on HIV-1 Protease.

  摘要：

  从锁阳（Cynomorium songaricum RUPR.）茎的CH2Cl2和MeOH提取物中，分离得到了熊果酸及其丙二酸氢化物，它们是人类免疫缺陷病毒1型（HIV-1）蛋白酶的抑制剂，其半数抑制浓度（IC50）分别为8和6微摩尔。在合成的各种相关三萜二羧酸半酯中，对于熊果酸、齐墩果酸和白桦脂酸等三萜类化合物，抑制活性倾向于按草酰、丙二酰、琥珀酰和戊二酰半酯的顺序增加。其中，戊二酰半酯显示出最强的抑制作用，IC50为4微摩尔。从锁阳茎的水提取物中，还发现了由表儿茶素构成扩展单元的黄烷-3-醇聚合物，它们也是HIV-1蛋白酶的强效抑制剂。

  DOI：

  10.1248/cpb.47.141
• 作为产物：
  描述：

  熊果酸 在 吡啶 、 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.0h， 生成 3β-[(4-carboxyl)butyryloxy]-urs-12-en-28-oic acid
  参考文献：
  名称：

  A hydrophilic conjugate approach toward the design and synthesis of ursolic acid derivatives as potential antidiabetic agent

  摘要：

  在这项研究中，成功设计并合成了一系列新颖的熊果酸（UA）衍生物，通过在3-OH和/或17-COOH位置结合亲水和极性基团。

  DOI：

  10.1039/c5ra05450h

文献信息

• Discovery of pentacyclic triterpene 3β-ester derivatives as a new class of cholesterol ester transfer protein inhibitors
  作者：Dongyin Chen、Xin Huang、Hongwen Zhou、Hanqiong Luo、Pengfei Wang、Yongzhi Chang、Xinyi He、Suiying Ni、Qingqing Shen、Guoshen Cao、Hongbin Sun、Xiaoan Wen、Jun Liu

  DOI：10.1016/j.ejmech.2017.08.012

  日期：2017.10

  A series of pentacyclic triterpene 3β-ester derivatives were designed, synthesized and evaluated as a new class of cholesteryl ester transfer protein (CETP) inhibitors for the treatment of dyslipidemia. In vitro screening assay showed that 5 out of 30 compounds displayed moderate inhibiting human CETP activity with IC50s less than 10 μM. Among them, compound 20 (IC50 = 2.3 μM) had the most potent biological

  设计，合成和评估了一系列五环三萜3β-酯衍生物，将其作为治疗血脂异常的一类新的胆固醇酯转移蛋白（CETP）抑制剂。体外筛选试验表明，30种化合物中有5种显示出适度的抑制人CETP活性，IC 50小于10μM。其中，化合物20（IC 50  = 2.3μM）具有最强的生物学活性，可有效改善人脂肪组织特异性CETP转基因（ap2-CETPTg）小鼠和豚鼠的血浆脂质水平。额外的安全性评估（豚鼠没有血压升高）和药代动力学研究表明，化合物20的潜在可药性 这是开发用于治疗血脂异常的新型CETP抑制剂的有希望的先导。
• A hydrophilic conjugate approach toward the design and synthesis of ursolic acid derivatives as potential antidiabetic agent
  作者：TianMing Huang、PanPan Wu、AnMing Cheng、Jing Qin、Kun Zhang、SuQing Zhao

  DOI：10.1039/c5ra05450h

  日期：——

  In this study, a series of novel ursolic acid (UA) derivatives were designed and synthesized successfully via conjugation of hydrophilic and polar groups at 3-OH and/or 17-COOH position.

  在这项研究中，成功设计并合成了一系列新颖的熊果酸（UA）衍生物，通过在3-OH和/或17-COOH位置结合亲水和极性基团。
• Anti-AIDS Agents 38. Anti-HIV Activity of 3-<i>O</i>-Acyl Ursolic Acid Derivatives
  作者：Yoshiki Kashiwada、Tsuneatsu Nagao、Ayumi Hashimoto、Yasumasa Ikeshiro、Hikaru Okabe、L. Mark Cosentino、Kuo-Hsiung Lee

  DOI：10.1021/np990633v

  日期：2000.12.1

  Based on our previous finding that 3-O-acyl-betulinic and -oleanolic acids, especially the 3-O-(3',3'-dimethyl)-succinyl derivatives (2 and 4), demonstrated potent anti-HIV activity [EC50 < 0.00035 and 0.00086 M; therapeutic index (TI) > 20 000 and 22 326, respectively], several 3-O-acyl-ursolic acids were prepared and evaluated for anti-HIV activity. Ursolic acid (6) was equipotent (EC50 4.4 muM) with oleanolic acid (EC50 3.7 muM), although it was slightly toxic (IC50 14.3 CIM, TI 3.3). 3-O-Diglycoryl-ursolic acid (10) demonstrated relatively potent anti-HIV activity with an EC50 of 0.31 muM and a TI of 155.5. In contrast, 3-O-(3',3'-dimethylsuccinyl)-ursolic acid (8), which is analogous to the extremely potent anti-HIV betulinic acid and oleanolic acid derivatives 2 and 4, displayed only weak anti-HIV activity (EC50 2.1 muM, TI 23.6).
• Inhibitory Effects of Constituents from Cynomorium songaricum and Related Triterpene Derivatives on HIV-1 Protease.
  作者：Chaomei MA、Norio NAKAMURA、Hirotsugu MIYASHIRO、Masao HATTORI、Kunitada SHIMOTOHNO

  DOI：10.1248/cpb.47.141

  日期：——

  From CH2Cl2 and MeOH extracts of the stems of Cynomorium songaricum RUPR. (Cynomoriaceae), ursolic acid and its hydrogen malonate were isolated as inhibitors of human immunodeficiency virus type 1 (HIV-1) protease, with 50% inhibitory concentrations (IC50) of 8 and 6 μM, respectively. Amongst various synthesized dicarboxylic acid hemiesters of related triterpenes, inhibitory activity tended to increase in the order of oxalyl, malonyl, succinyl and glutaryl hemiesters, for triterpenes such as ursolic acid, oleanolic acid and betulinic acid. The most potent inhibition was observed for the glutaryl hemiesters, with an IC50 of 4 μM.From the water extract of the stems of C. songaricum, flavan-3-ol polymers, consisting of epicatechin as their extender flavan units, were also found to be potent inhibitory principles against HIV-1 protease.

  从锁阳（Cynomorium songaricum RUPR.）茎的CH2Cl2和MeOH提取物中，分离得到了熊果酸及其丙二酸氢化物，它们是人类免疫缺陷病毒1型（HIV-1）蛋白酶的抑制剂，其半数抑制浓度（IC50）分别为8和6微摩尔。在合成的各种相关三萜二羧酸半酯中，对于熊果酸、齐墩果酸和白桦脂酸等三萜类化合物，抑制活性倾向于按草酰、丙二酰、琥珀酰和戊二酰半酯的顺序增加。其中，戊二酰半酯显示出最强的抑制作用，IC50为4微摩尔。从锁阳茎的水提取物中，还发现了由表儿茶素构成扩展单元的黄烷-3-醇聚合物，它们也是HIV-1蛋白酶的强效抑制剂。
• Synthesis, biological evaluation and SAR studies of ursolic acid 3β-ester derivatives as novel CETP inhibitors
  作者：Chao Chen、Renhua Sun、Yan Sun、Xuan Chen、Fei Li、Xiaoan Wen、Haoliang Yuan、Dongyin Chen

  DOI：10.1016/j.bmcl.2019.126824

  日期：2020.1

  Cholesteryl ester transfer protein (CETP) is an attractive therapeutic target for the prevention and treatment of cardiovascular diseases by lowering low-density lipoprotein cholesterol levels as well as raising high-density lipoprotein cholesterol levels in human plasma. Herein, a series of ursolic acid 3 beta-ester derivatives were designed, synthesized and evaluated for the CETP inhibiting activities. Among these compounds, the most active compound is U12 with an IC50 value of 2.4 mu M in enzymatic assay. The docking studies showed that the possible hydrogen bond interactions between the carboxyl groups at both ends of the molecule skeleton and several polar residues (such as Ser191, Cys13 and Ser230) in the active site region of CETP could significantly enhance the inhibition activity. This study provides structural insight of the interactions between these pentacyclic tri-terpenoid 3 beta-ester derivatives and CETP protein for the further modification and optimization.