propargyl-(2α,3β)-2,3-dihydroxyolean-12-en-28-oate | 1243271-21-7

• 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: propargyl-(2α,3β)-2,3-dihydroxyolean-12-en-28-oate
• 英文别名: prop-2-ynyl (4aS,6aR,6aS,6bR,8aR,10R,11R,12aR,14bS)-10,11-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylate
• CAS: 1243271-21-7
• 化学式: C₃₃H₅₀O₄
• 分子量: 510.758
• InChiKey: WJRDKCLGVFADJL-RBNDYAJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  37
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  propargyl-(2α,3β)-2,3-dihydroxyolean-12-en-28-oate 在 copper(ll) sulfate pentahydrate 、 水 、 sodium ascorbate 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 13.0h， 生成 2-[4-(2α,3β-dihydroxyolean-12-en-28-carbonyloxymethyl)-1H-1,2,3-triazol-1-yl]acetic acid
  参考文献：
  名称：

  Tethered derivatives of d-glucose and pentacyclic triterpenes for homo/heterobivalent inhibition of glycogen phosphorylase

  摘要：

  五环三萜的 C-28 羧酸（齐墩果酸、熊果酸和山楂酸）的炔丙酯与 2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖基叠氮化物以及 N-( ω-叠氮基-[C-2、C-6和C-11]烷酰基)-β-D-吡喃葡萄糖胺在铜(I)催化的叠氮化物-炔环加成(CuAAC)条件下生成束缚的D-葡萄糖-三萜异共轭物。通过碱催化水解除去O-乙酰基保护基团。 N-(ω-叠氮基-[C-2、C-6、C-11 和 C-16]烷酰基)-β-D-吡喃葡萄糖胺也在 CuAAC 条件下被 1,7-辛二炔束缚以提供 D-葡萄糖同缀合物。 O-脱乙酰化通过 Zemplén 方案进行。新化合物针对兔肌糖原磷酸化酶 (RMGP) a 或 b 酶进行了检测。一些杂合物在低微摩尔范围内抑制酶（IC50 值 40-70 μM），而同聚物作为抑制剂被证明是无效的。

  DOI：

  10.1039/b9nj00602h
• 作为产物：
  描述：

  山楂酸 、 3-溴丙炔 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 propargyl-(2α,3β)-2,3-dihydroxyolean-12-en-28-oate
  参考文献：
  名称：

  将山楂酸转化为酰基胆碱酯酶的有效抑制剂。

  摘要：

  在最近的十年中，已经评价了山楂酸的许多生物学特性，例如作为抗肿瘤剂或抗病毒剂以及作为营养保健品。在本通讯中更详细地研究了山楂酸和相关衍生物作为乙酰胆碱酯酶或丁酰胆碱酯酶抑制剂的潜力。在研究和治疗阿尔茨海默氏病和其他痴呆症方面，胆碱酯酶仍然代表了一组有趣的靶酶。尽管已经成功地测试了其他三萜酸作为胆碱酯酶抑制剂的能力，但是迄今为止，山楂酸还没有被纳入这类研究。因此，合成了在不同中心具有修饰的三个系列的山梨酸衍生物，并对其进行Ellman' s法测定其抑制强度和抑制作用类型。尽管母体化合物山楂酸在这些测定中不是抑制剂，但某些化合物在单位个微摩尔范围内表现出对乙酰胆碱酯酶的抑制作用。鉴定出两种化合物是丁酰胆碱酯酶的抑制剂，它们的抑制常数与加兰他敏（一种常用于治疗阿尔茨海默氏病的药物）的可比性相当。此外，还进行了额外的选择性和细胞毒性研究，突显了几种衍生物的潜力，并使它们有资格进一步研究。对接研究表

  DOI：

  10.1016/j.ejmech.2015.09.007

文献信息

• Microwave-assisted synthesis, anti-inflammatory and anti-proliferative activities of new maslinic acid derivatives bearing 1,5- and 1,4-disubstituted triazoles
  作者：Karim Chouaïb、Stéphanie Delemasure、Patrick Dutartre、Hichem Ben Jannet

  DOI：10.1080/14756366.2016.1193733

  日期：2016.11.2

  In this work, 40 analogs with a natural maslinic acid core (from Olea europaea L.) and various aromatic azides were synthesized. A regiospecific, facile and practical synthesis of 1,5-triazolyl derivatives by Ru(II)-catalyzed azide-alkyne cycloaddition (RuAAC), and mono-, bis- and tri-1,4-triazolyl derivatives by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) was described. All the reactions were

  在这项工作中，合成了40种具有天然山楂酸核心的类似物（来自Olea europaea L.）和各种芳香族叠氮化物。通过Ru（II）催化的叠氮化物-炔烃环加成（RuAAC）合成1,5-三唑基衍生物的区域特异性，简便且实用的合成方法，以及Cu（I）-描述了催化的叠氮化物-炔烃环加成反应（CuAAC）。所有反应均通过微波辐射进行，避免使用有毒的试剂和溶剂。通过简单纯化以几乎定量的产率从反应混合物中获得新产物，并且反应时间通常比文献报道的时间短。在广泛的光谱方法（包括ESI-HRMS，1D和2D-NMR）的基础上阐明了它们的化学结构。
• Strong Inhibitory Activity and Action Modes of Synthetic Maslinic Acid Derivative on Highly Pathogenic Coronaviruses: COVID-19 Drug Candidate
  作者：Raya Soltane、Amani Chrouda、Ahmed Mostafa、Ahmed A. Al-Karmalawy、Karim Chouaïb、Abdelwaheb dhahri、Rami Adel Pashameah、Ahlam Alasiri、Omnia Kutkat、Mahmoud Shehata、Hichem Ben Jannet、Jawhar Gharbi、Mohamed A. Ali

  DOI：10.3390/pathogens10050623

  日期：——

  (17) structural analogues prepared from natural maslinic and oleanolic acids, screened against SARS-CoV-2 main protease. Furthermore, we experimentally validated the virtual data by measuring the half-maximal cytotoxic and inhibitory concentrations of each compound. Interestingly, the chlorinated isoxazole linked maslinic acid (compound 17) showed promising antiviral activity at micromolar non-toxic

  2019 年 12 月下旬，一种新型冠状病毒，即严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2)，逃脱了动物与人类的接触，并成为一场持续的全球大流行，伴有严重的流感样疾病，通常称为 2019 年冠状病毒病（2019冠状病毒病）。在本研究中，对由天然山楂酸和齐墩果酸制备的十七 ( 17 ) 个结构类似物进行了分子对接研究，针对 SARS-CoV-2 主要蛋白酶进行了筛选。此外，我们通过测量每种化合物的半最大细胞毒性和抑制浓度来实验验证虚拟数据。有趣的是，氯化异恶唑连接的山楂酸（化合物17 ）在微摩尔无毒浓度下显示出有希望的抗病毒活性。经过深思熟虑，我们发现化合物17主要损害 SARS-CoV-2 的病毒复制。此外，针对所检查的化合物进行了一项非常有前景的 SAR 研究，药物化学家在不久的将来可以将其用于设计和合成潜在的抗 SARS-CoV-2 候选药物。我们的结果对于在进一步获得 COVID-19
• Maslinic and oleanolic acids derivatives for treating SARS-CoV-2 infection
  申请人：King Abdulaziz University

  公开号：US11266632B1

  公开（公告）日：2022-03-08

  Provided are methods of using oleanolic acid and derivatives for treating coronavirus infection. The method includes using propargyl-moiety containing oleanolic acid derivatives for inhibiting coronavirus growth by impairing the viral replication of SARS-CoV-2 through inhibition of the viral function of SARS-CoV-2 main protease.

  提供了使用齐墩果酸及其衍生物治疗冠状病毒感染的方法。该方法包括使用含丙炔基的齐墩果酸衍生物来抑制冠状病毒的生长，通过抑制SARS-CoV-2病毒主蛋白的病毒功能来干扰病毒复制。
• Esters and amides of maslinic acid trigger apoptosis in human tumor cells and alter their mode of action with respect to the substitution pattern at C-28
  作者：Bianka Siewert、Elke Pianowski、René Csuk

  DOI：10.1016/j.ejmech.2013.10.016

  日期：2013.12

  Cancer is one of the most commonly diagnosed diseases worldwide; its mortality rate is high, and there is still a demand for the development of antitumor active drugs. Triterpenoic acids show many pharmacological effects, among them antitumor activity. One of these, maslinic acid-1 is of interest because of its antitumor profile. It is not only cytotoxic but also triggers apoptosis in various human tumor cell lines. To improve the cytotoxicity of parent 1 we set out to synthesize a series of esters and amides differing in structure and lipophilicity. These compounds were tested in a sulforhodamine B assay for cytotoxicity, and screened for their ability to induce apoptosis using an acridine orange/propidium iodide assay, DNA laddering and cell cycle experiments. Esters containing small-chain, lipophilic residues increased the cytotoxicity whereas amides as well long-chain esters led to a decrease in activity. The antitumor activity seems to be independent from the substitution pattern at position C-28 for esters and amides but alters their mode of action. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Design and semisynthesis of new herbicide as 1,2,3-triazole derivatives of the natural maslinic acid
  作者：Aymen Ben Nejma、Mansour Znati、Adam Daich、Mohamed Othman、Ata Martin Lawson、Hichem Ben Jannet

  DOI：10.1016/j.steroids.2018.07.004

  日期：2018.10

  Interesting biological activities (anti-inflammatory, anticancer, antiviral, antioxidant, antidiabetic...) have been reported for maslinic acid (MA) and MA-based compounds. In continuation of our previous work on MA, herbicide potential of Tunisian plant extracts and 1,4-triazolyl derivatives of MA, we now wish to report semisynthesis of new MA-based triazole hybrid compounds with herbicide potential. These compounds were synthesized through Cu-catalyzed azide-alkyne cycloaddition (CuAAC) under microwave irradiation conditions between propargylated MA and a series of phthalimide azides. Here, the first partner of CuAAC reaction (propargylated MA) resulted from propargylation of C-28 carboxylic acid group of isolated MA from the well-known Mediterranean plant Olea europaea L. (Oleaceae). So far, phthalimide azide derivatives were achieved by trapping of N-acyliminium ion, in-situ generated under catalytic condition of Bi(OTf)(3), by aromatic nucleophiles. The cycloaddition reaction afforded regiospecifically 1,4-disubstituted triazoles in good yields. The latter hybrid compounds were shown to exhibit a high inhibition potential of seed germination. This constitutes the first step in development of potent herbicides since one of the final semisynthesized structures can serve as a promising lead candidate for further studies.