3β-[(4-carboxyl)butyryloxy]-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: 3β-[(4-carboxyl)butyryloxy]-olean-12-en-28-oic acid
• 英文别名: Oleanolic acid 3-O-glutarate；(4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-(4-carboxybutanoyloxy)-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid
• 化学式: C₃₅H₅₄O₆
• 分子量: 570.81
• InChiKey: NVEQPGMRTSPJGZ-FVWYBJPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 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]-olean-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Pentanedioic acid (3S,4aR,6aR,6bS,8aS,12aS,14aR,14bR)-8a-methoxycarbonyl-4,4,6a,6b,11,11,14b-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydro-picen-3-yl ester methyl ester
  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：

  戊二酸酐 、 齐墩果酸 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 生成 3β-[(4-carboxyl)butyryloxy]-olean-12-en-28-oic acid
  参考文献：
  名称：

  抗艾滋病剂。30.齐墩果酸，多聚果酸和与结构相关的三萜类化合物的抗HIV活性。

  摘要：

  齐墩果酸（1）已从多种植物中鉴定为抗HIV成分，包括蔷薇木（叶子），甘蓝Prosopis glandulosa（叶子和嫩枝），杜鹃花（整个植物），蒲桃（叶子），Hyptis capitata（整个植物） ）和Ternstromia Gymnanthera（空中部分）。它抑制EC-1值为1.7 microg / mL的急性感染H9细胞中的HIV-1复制，并抑制IC50值为21.8 microg / mL的H9细胞生长[治疗指数（TI）12.8]。分离自伍兹木和人参中的波摩尔酸也被鉴定为抗HIV药物（EC50为1.4 microg / mL，TI 16.6）。尽管熊果酸确实显示出抗HIV活性（EC50为2.0微克/毫升），但毒性微弱（IC50为6.5微克/毫升，TI 3.3）。还从伍德氏木。的CHCl3可溶级分中分离出了新的三萜（11），尽管它没有显示抗HIV活性。通过光谱检查确定11的结构为

  DOI：

  10.1021/np9800710

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。
• Synthesis and anti-HIV activity of oleanolic acid derivatives
  作者：Yong-Ming Zhu、Jing-Kang Shen、Hui-Kang Wang、L.Mark Cosentino、Kuo-Hsiung Lee

  DOI：10.1016/s0960-894x(01)00647-3

  日期：2001.12

  Thirteen oleanolic acid derivatives were prepared and evaluated for anti-HIV activity in H9 lymphocytes. Saturating the C(12)-C(13) double bond and converting the C(17)-carboxyl group to an aminomethyl group led to compounds 13-15 and 19-20, respectively, which showed improved anti-HIV activity. Compound 15 was the most potent derivative with EC(50)=0.0039 microg/mL and TI=3570.

  制备了十三种齐墩果酸衍生物，并评估了其在H9淋巴细胞中的抗HIV活性。饱和C（12）-C（13）双键并将C（17）-羧基转化为氨甲基导致化合物13-15和19-20分别显示出改进的抗HIV活性。化合物15是最有效的衍生物，EC（50）= 0.0039 microg / mL，TI = 3570。
• Semi-synthesis of acylated triterpenes from olive-oil industry wastes for the development of anticancer and anti-HIV agents
  作者：Andres Parra、Samuel Martin-Fonseca、Francisco Rivas、Fernando J. Reyes-Zurita、Marta Medina-O'Donnell、Antonio Martinez、Andres Garcia-Granados、Jose A. Lupiañez、Fernando Albericio

  DOI：10.1016/j.ejmech.2013.12.049

  日期：2014.3

  A broad set of potential bioactive conjugate compounds has been semi-synthesized through solution and solid-phase organic procedures, coupling two natural pentacyclic triterpene acids, oleanolic (OA) and maslinic acids (MA), at the hydroxyl groups of the A-ring of the triterpene skeleton, with 10 different acyl groups. These acyl OA and MA derivatives have been tested for their anti-proliferative (against the bl6f10 murine melanoma cancer cells) and antiviral (as inhibitors of the HIV-1-protease) effects. Several derivatives have shown high levels of early and total apoptosis (up to 90%). Most of the compounds that exhibited anti-proliferative effects also generated ROS, probably involving the activation of an intrinsic apoptotic route. The only four compounds that did not cause the release of ROS could be related to the participation of a probable extrinsic activation of the apoptosis mechanism. A great number of these acyl OA and MA derivatives have proved to be potent inhibitors of the HIV-1-protease, the most active inhibitors having IC50 values between 0.31 and 15.6 mu M, these values being between 4 and 186 times lower than their non-acylated precursors. The potent activities exhibited in the apoptosis-activation processes and in the inhibition of the HIV-1-protease by some OA and MA acylated derivatives imply that these compounds could be used as new, safe, and effective anticancer and/or antiviral drugs. (C) 2014 Elsevier Masson SAS. All rights reserved.