argolide | 126871-96-3

• 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: argolide
• 英文别名: 4-epitansanin；(3aS,6E,10R,11aR)-6,10-dimethyl-3-methylidene-4,5,8,10,11,11a-hexahydro-3aH-cyclodeca[b]furan-2,9-dione
• CAS: 126871-96-3
• 化学式: C₁₅H₂₀O₃
• 分子量: 248.322
• InChiKey: WBBCIKNHTYTDRA-YYYMEZEWSA-N

物化性质

• 熔点：
  133-135 °C(Solv: dichloromethane (75-09-2); ethyl ether (60-29-7))
• 沸点：
  416.9±45.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  argolide 在 三氟过氧乙酸 、 sodium carbonate 作用下， 以 二氯甲烷 为溶剂， 以87%的产率得到argolide epoxide
  参考文献：
  名称：

  Chemical modification of argolide

  摘要：

  Chemical transformations have been made of argolide, a sesquiterpene lactone of the germacrane type, as a result of which new epoxy, amino, and hydroxy derivatives of it have been obtained.

  DOI：

  10.1007/bf02234926

文献信息

• Synthesis of 13-Aryl Derivatives of the Sesquiterpene Lactone Argolide and their Analgesic Activity
  作者：A. E. Esenbaeva、E. E. Shul’ts、Yu. V. Gatilov、M. M. Shakirov、S. S. Patrushev、G. A. Atazhanova、A. B. Kenesheva、S. M. Adekenov

  DOI：10.1007/s10600-013-0768-9

  日期：2013.11

  13-Aryl-substituted derivatives of the germacranolide argolide were synthesized by a Heck reaction with arylhalides. The structure of (E)-13-(4-methoxyphenyl)-3-oxogermacra-1(10),11(13)-dien-6α,12-olide was proved by an x-ray crystal structure analysis. Analgesic activity was found in the acetic-acid writhing test for the 13-arylgermacranolides.

  通过与芳基卤化物的 Heck 反应，合成了 13-芳基取代的胚芽鞘内酯 argolide 衍生物。通过 X 射线晶体结构分析，证实了 (E)-13-(4- 甲氧基苯基)-3-氧代孕甾-1(10),11(13)-二烯-6α,12-内酯的结构。在醋酸扭动试验中发现，13-芳基锗酸内酯具有镇痛活性。
• Bimolecular Compounds Based on Natural Metabolites
  作者：S. M. Adekenov、A. S. Kishkentaeva、Zh. R. Shaimerdenova、G. A. Atazhanova

  DOI：10.1007/s10600-018-2380-5

  日期：2018.5

  New alkaloid-containing derivatives of the sesquiterpene lactones arglabin, grosshemin, 3,4β-epoxyarglabin, argolide, and parthenolide were prepared for the first time. Their structures were studied using PMR, 13C NMR, and mass spectra and an X-ray crystal structure analysis. Chemo- and regioselective reactions of the sesquiterpene lactones and alkaloids were observed. The synthesized compounds exhibited

  首次制备了倍半萜内酯 arglabin、groshemin、3,4β-epoxyarglabin、argolide 和小白菊内酯的新型含生物碱衍生物。使用 PMR、13C NMR、质谱和 X 射线晶体结构分析研究了它们的结构。观察到倍半萜内酯和生物碱的化学和区域选择性反应。合成的化合物表现出驱虫和保肝活性和细胞毒性。
• Molecular and crystal structure of the germacranolide argolide from Artemisia glabella
  作者：S. M. Adekenov、K. A. Aituganov、K. M. Turdybekov、S. V. Lindeman、Yu. T. Struchkov

  DOI：10.1007/bf00630358

  日期：1991.9

  The new germacranolide argolide has been isolated from the epigeal part ofArtemisia glabella, and its structure has been shown by its conversion into oxopelenolide B. From the results of an x-ray investigation it is suggested that argolide has the spatial structure of 3-oxo-4α,7α,6β(H)-germacra-1(10),11(13)-dien-6,12-olide.

  新的germacranolide argolide 已从青蒿的表皮部分分离出来，其结构通过转化为oxopelenolide B 而显示出来。X 射线调查结果表明，argolide 具有3-oxo-的空间结构。 4α,7α,6β(H)-germacra-1(10),11(13)-dien-6,12-olide。
• Inhibition of T Cell Receptor Activation by Semi-Synthetic Sesquiterpene Lactone Derivatives and Molecular Modeling of Their Interaction with Glutathione and Tyrosine Kinase ZAP-70
  作者：Andrei Khlebnikov、Igor Schepetkin、Anarkul Kishkentaeva、Zhanar Shaimerdenova、Gayane Atazhanova、Sergazy Adekenov、Liliya Kirpotina、Mark Quinn

  DOI：10.3390/molecules24020350

  日期：——

  A variety of natural compounds have been shown to modulate T cell receptor (TCR) activation, including natural sesquiterpene lactones (SLs). In the present studies, we evaluated the biological activity of 11 novel semi-synthetic SLs to determine their ability to modulate TCR activation. Of these compounds, α -epoxyarglabin, cytisinyl epoxyarglabin, 1 β ,10 α -epoxyargolide, and chloroacetate grosheimin inhibited anti-CD3-induced Ca2+ mobilization and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in Jurkat T cells. We also found that the active SLs depleted intracellular glutathione (GSH) in Jurkat T cells, supporting their reactivity towards thiol groups. Because the zeta-chain associated tyrosine kinase 70 kDa (ZAP-70) is essential for TCR signaling and contains a tandem SH2 region that is highly enriched with multiple cysteines, we performed molecular docking of natural SLs and their semi-synthetic derivatives into the ZAP-70 binding site. The docking showed that the distance between the carbon atom of the exocyclic methylene group and the sulfur atom in Cys39 of the ZAP-70 tandem SH2 module was 3.04–5.3 Å for active compounds. Furthermore, the natural SLs and their derivatives could be differentiated by their ability to react with the Cys39 SH-group. We suggest that natural and/or semi-synthetic SLs with an α -methylene- γ -lactone moiety can specifically target GSH and the kinase site of ZAP-70 and inhibit the initial phases of TCR activation.

  各种天然化合物已被证明可以调节T细胞受体（TCR）的激活，包括天然的倍半萜内酯（SLs）。在这些研究中，我们评估了11种新型半合成SLs的生物活性，以确定它们调节TCR激活的能力。在这些化合物中，α-环氧基阿尔格拉宾、细胞素环氧基阿尔格拉宾、1β,10α-环氧基阿戈利德和氯乙酸盖罗海明抑制了抗CD3诱导的Jurkat T细胞中Ca2+的mobilization和细胞外信号调节激酶1/2（ERK1/2）的磷酸化。我们还发现，活性SLs使Jurkat T细胞中的细胞内谷胱甘肽（GSH）耗尽，支持它们对巯基的反应性。因为zeta链相关酪氨酸激酶70千道尔（ZAP-70）对于TCR信号传导至关重要，并含有一个高度富含多个半胱氨酸的串联SH2区域，我们对天然SLs及其半合成衍生物进行了分子对接到ZAP-70结合位点。对接显示，活性化合物的外环亚甲基基团的碳原子与ZAP-70串联SH2模块的Cys39的硫原子之间的距离为3.04-5.3 Å。此外，天然SLs及其衍生物可通过它们与Cys39SH基团的反应能力进行区分。我们建议具有α-亚甲基-γ-内酯基团的天然和/或半合成SLs可以特异性靶向GSH和ZAP-70的激酶位点，并抑制TCR激活的初始阶段。
• ADEKENOV, S. M.;AJTUGANOV, K. A.;RALDUGIN, V. A.;GATILOV, YU. V.;BAGRYANS+, IZV. AN KAZSSR. CEP. XIM.,(1989) N, S. 79-88
  作者：ADEKENOV, S. M.、AJTUGANOV, K. A.、RALDUGIN, V. A.、GATILOV, YU. V.、BAGRYANS+

  DOI：——

  日期：——