1,10-epoxycostunolide | 29484-23-9

• 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: 1,10-epoxycostunolide
• 英文别名: costunolide 1,10-epoxide；(1S,4S,6R,9E,11R)-4,9-dimethyl-14-methylidene-5,12-dioxatricyclo[9.3.0.04,6]tetradec-9-en-13-one
• CAS: 29484-23-9
• 化学式: C₁₅H₂₀O₃
• 分子量: 248.322
• InChiKey: GEKKXBNQQCFXAH-YQWLLGBWSA-N

物化性质

• 沸点：
  400.2±45.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,10-epoxycostunolide 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 (+)-1,10-epoxy-11β,13-dihydrocostunolide
  参考文献：
  名称：

  Sesquiterpene Lactones with Potential Use as Natural Herbicide Models (I):  trans,trans-Germacranolides

  摘要：

  A structure-activity study to evaluate the effect of the trans,trans-germacranolide sesquiterpene lactones costunolide, parthenolide, and their 1,10-epoxy and 11,13-dihydro derivatives (in a range of 100-0.001 mu M) on the growth and germination of several mono and dicotyledon target species is accomplished. Results are compared with those obtained in the same bioassay with an internal standard, the commercial herbicide Logran, to validate the results with a known active formulation and to compare the results with a commercial product to test their potential use as natural herbicide models. These compounds appear to have a more selective effects on the radicle growth of monocotyledons. Certain factors such as the presence of nucleophile-acceptor groups and their accessibility enhance the inhibitory activity. The levels of radicle inhibition obtained with some compounds on wheat are totally comparable to those of Logran and allow to propose them as lead compounds.

  DOI：

  10.1021/jf9903612
• 作为产物：
  描述：

  木香烃内酯 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 以47.5 %的产率得到1,10-epoxycostunolide
  参考文献：
  名称：

  发现新型倍半萜内酯衍生物作为治疗溃疡性结肠炎的有效 PKM2 激活剂

  摘要：

  丙酮酸激酶M2（PKM2）可显着影响Th17和Treg细胞的分化；因此，它被认为是 UC 治疗的一个有前途的靶点。在此，设计、合成了五个系列的木香烯内酯（Cos ）衍生物，并进行了生物学评价。其中，D5对 T 细胞增殖表现出优异的免疫调节活性和有效的 PKM2 激活活性。同时，已证实D5也能与PKM2的Cys424共价相互作用。分子对接和分子动力学 (MD) 研究表明，D5的二氟环丙基衍生物通过与 Arg399 静电相互作用改善蛋白质-配体相互作用。此外，D5显着抑制 Th17 而非 Treg 细胞的分化，从而恢复 Th17/Treg 平衡，这归因于抑制 PKM2 介导的糖酵解。口服D5可改善小鼠模型中葡聚糖硫酸钠 (DSS) 和 2,4,6-三硝基苯磺酸 (TNBS) 诱导的结肠炎症状。总的来说，D5有潜力被开发为新型抗 UC 候选药物。

  DOI：

  10.1021/acs.jmedchem.2c01856

文献信息

• Effects of Solvents and Water in Ti(III)-Mediated Radical Cyclizations of Epoxygermacrolides. Straightforward Synthesis and Absolute Stereochemistry of (+)-3α-Hydroxyreynosin and Related Eudesmanolides
  作者：Alejandro F. Barrero、J. Enrique Oltra、Juan M. Cuerva、Antonio Rosales

  DOI：10.1021/jo016277e

  日期：2002.4.1

  was carried out using different solvents and additives to develop an expeditious procedure for the synthesis of natural eudesmanolides via free-radical chemistry. In the nonhalogenated solvents THF, benzene, and toluene the transannular cyclization, initiated by the homolytic opening of the oxirane ring, selectively led to the desired exocyclic alkene 5. When water was added to THF, however, the main

  Cp（2）TiCl介导的1,10-环氧-11beta，13-二氢木香酚（4）的重排使用不同的溶剂和添加剂进行，以开发通过自由基化学合成天然eudesmanolides的快速程序。在非卤代溶剂THF，苯和甲苯中，由环氧乙烷环的均相开环引发的环环环化选择性地导致形成所需的环外烯烃5.然而，将水添加到THF中时，主要产物是还原的奥德曼醇化物8。 D（2）O的实验证实8的H-4来自水。为了使这些结果合理化，提出了一种基于水溶剂化的Cp（2）TiCl复合物的机理假说。最后，在化学制备（+）-3α-羟基雷诺菌素（1）和（+）-雷诺菌素（17）的关键步骤中，已证明使用该试剂可证明Cp（2）TiCl可以用于合成天然奥地香奈德。这些合成证实了1的化学结构，并建立了天然产物1和17的绝对立体化学。获得的结果表明，采用仿生策略与Ti（III）介导的自由基化学的结合可能代表了一种对映体特异性合成170多种在C-4
• Sesquiterpene Lactones with Potential Use as Natural Herbicide Models (I):  <i>trans,trans-</i>Germacranolides
  作者：Francisco A. Macías、Juan C. G. Galindo、Diego Castellano、Raúl F. Velasco

  DOI：10.1021/jf9903612

  日期：1999.10.1

  A structure-activity study to evaluate the effect of the trans,trans-germacranolide sesquiterpene lactones costunolide, parthenolide, and their 1,10-epoxy and 11,13-dihydro derivatives (in a range of 100-0.001 mu M) on the growth and germination of several mono and dicotyledon target species is accomplished. Results are compared with those obtained in the same bioassay with an internal standard, the commercial herbicide Logran, to validate the results with a known active formulation and to compare the results with a commercial product to test their potential use as natural herbicide models. These compounds appear to have a more selective effects on the radicle growth of monocotyledons. Certain factors such as the presence of nucleophile-acceptor groups and their accessibility enhance the inhibitory activity. The levels of radicle inhibition obtained with some compounds on wheat are totally comparable to those of Logran and allow to propose them as lead compounds.
• Discovery of Novel Sesquiterpene Lactone Derivatives as Potent PKM2 Activators for the Treatment of Ulcerative Colitis
  作者：Ping Wang、Hongqiong Yang、Weijiang Lin、Jingxian Zhou、Yi Liu、Lingyu Ma、Mengting Li、Yang Hu、Chengli Yu、Yinan Zhang、Qi Lv、Jian Liu、Lihong Hu

  DOI：10.1021/acs.jmedchem.2c01856

  日期：2023.4.27

  The pyruvate kinase M2 (PKM2) can significantly affect the differentiation of Th17 and Treg cells; thus, it is considered a promising target for UC therapy. Herein, five series of costunolide (Cos) derivatives are designed, synthesized, and biologically evaluated. Among them, D5 exhibits excellent immunomodulatory activity against T-cell proliferation and potent PKM2 activating activity. Meanwhile, it

  丙酮酸激酶M2（PKM2）可显着影响Th17和Treg细胞的分化；因此，它被认为是 UC 治疗的一个有前途的靶点。在此，设计、合成了五个系列的木香烯内酯（Cos ）衍生物，并进行了生物学评价。其中，D5对 T 细胞增殖表现出优异的免疫调节活性和有效的 PKM2 激活活性。同时，已证实D5也能与PKM2的Cys424共价相互作用。分子对接和分子动力学 (MD) 研究表明，D5的二氟环丙基衍生物通过与 Arg399 静电相互作用改善蛋白质-配体相互作用。此外，D5显着抑制 Th17 而非 Treg 细胞的分化，从而恢复 Th17/Treg 平衡，这归因于抑制 PKM2 介导的糖酵解。口服D5可改善小鼠模型中葡聚糖硫酸钠 (DSS) 和 2,4,6-三硝基苯磺酸 (TNBS) 诱导的结肠炎症状。总的来说，D5有潜力被开发为新型抗 UC 候选药物。