3-O-(3',3'-dimethylglutaryl)oleanolic 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-O-(3',3'-dimethylglutaryl)oleanolic acid
• 英文别名: (4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-(4-carboxy-3,3-dimethylbutanoyl)oxy-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: C₃₇H₅₈O₆
• 分子量: 598.864
• InChiKey: RRSVWLBREHQZBN-MINDXIOPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  43
• 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

• 作为产物：
  描述：

  3,3-二甲基戊二酸酐 、 齐墩果酸 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 反应 36.0h， 以57.1%的产率得到3-O-(3',3'-dimethylglutaryl)oleanolic acid
  参考文献：
  名称：

  Chemical Modification of Oleanene Type Triterpenes and Their Inhibitory Activity against HIV-1 Protease Dimerization.

  摘要：

  合成了不同长度的3-O-酸性酰基链的齐墩果酸衍生物，并评估其对HIV-1蛋白酶的抑制活性。酸性链的长度经过优化为6和8个碳。将3-酯键更改为酰胺键或三萜的二聚化保留了它们对HIV-1蛋白酶的抑制活性。在齐墩果酸C-28位引入额外的酸性链显著提高了抑制活性，尽管只在C-28位连接一个酸性链的衍生物同样对HIV-1蛋白酶表现出强效活性。通过尺寸排阻色谱直接证明了抑制机制为对酶多肽二聚化的抑制。在温和碱性条件下，发现三萜衍生物的酯键对脂肪酶具有稳定性。

  DOI：

  10.1248/cpb.48.1681

文献信息

• Anti-AIDS Agents. 30. Anti-HIV Activity of Oleanolic Acid, Pomolic Acid, and Structurally Related Triterpenoids
  作者：Yoshiki Kashiwada、Hui-Kang Wang、Tsuneatsu Nagao、Susumu Kitanaka、Ichiro Yasuda、Toshihiro Fujioka、Takashi Yamagishi、L. Mark Cosentino、Mutsuo Kozuka、Hikaru Okabe、Yasumasa Ikeshiro、Chang-Qi Hu、Eric Yeh、Kuo-Hsiung Lee

  DOI：10.1021/np9800710

  日期：1998.9.1

  with an IC50 value of 21.8 microg/mL [therapeutic index (T. I.) 12.8]. Pomolic acid, isolated from R. woodsii and H. capitata, was also identified as an anti-HIV agent (EC50 1.4 microg/mL, T. I. 16.6). Although ursolic acid did show anti-HIV activity (EC50 2.0 microg/mL), it was slightly toxic (IC50 6.5 microg/mL, T. I. 3.3). A new triterpene (11) was also isolated from the CHCl3-soluble fraction of

  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
• 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.
• Synthesis and evaluation of potential complement inhibitory semisynthetic analogs of oleanolic acid
  作者：Haregewein Assefa、Alison Nimrod、Larry Walker、Robert Sindelar

  DOI：10.1016/s0960-894x(99)00314-5

  日期：1999.7

  A number of semisynthetic analogs of oleanolic acid have been synthesized and tested for their complement inhibitory, cytotoxic and apoptotic activities. Among these, compounds 10 and 17 exhibited complement inhibitory potency superior to oleanolic acid. Both have also shown a moderate improvement in in vitro therapeutic index (T.I.). (C) 1999 Elsevier Science Ltd. All rights reserved.