xyloketal B | 1229114-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: xyloketal B
• 英文别名: (+/-)-Xyloketal B；4,7,15,18-tetramethyl-3,5,14,16-tetraoxapentacyclo[11.7.0.02,10.04,8.015,19]icosa-1(13),2(10),11-trien-11-ol
• CAS: 1229114-42-4
• 化学式: C₂₀H₂₆O₅
• 分子量: 346.423
• InChiKey: CCNANHBVUNZCKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 xyloketal B 在 盐酸 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以82%的产率得到12-[(11-Hydroxy-4,7,15,18-tetramethyl-3,5,14,16-tetraoxapentacyclo[11.7.0.02,10.04,8.015,19]icosa-1,10,12-trien-12-yl)methyl]-4,7,15,18-tetramethyl-3,5,14,16-tetraoxapentacyclo[11.7.0.02,10.04,8.015,19]icosa-1,10,12-trien-11-ol
  参考文献：
  名称：

  Design and Synthesis of Novel Xyloketal Derivatives and Their Vasorelaxing Activities in Rat Thoracic Aorta and Angiogenic Activities in Zebrafish Angiogenesis Screen

  摘要：

  A novel series of xyloketal derivatives (1-21) were designed and prepared. The majority of the compounds demonstrated vasorelaxation action on 60 mM KCl-induced contractions rat isolated aortic rings in a concentration-dependent manner, and the action is mediated by both endothelium-independent and endothelium-dependent mechanisms. Compounds 9, 12, 13, 14, 15, and 19 showed higher vasorelaxation activities comparing with the lead compound 3. In addition, these derivatives had potential protective action against oxLDL-induced endothelial oxidative injury and enhanced NO production in HUVECs without toxic effects. The NO release was completely inhibited by eNOS inhibitor L-NAME. Furthermore, 3 significantly promoted the angiogenesis in zebrafish in a concentration-dependent manner at 0.1, 1, and 10 mu M. Compounds 9, 12, 14, 16, 20, and 21 exhibited stronger angiogenic activities than 3. Therefore, xyloketal derivatives are unique compounds with multiple pharmacological properties and may have potential implications in the treatment of cardiovascular diseases.

  DOI：

  10.1021/jm1001502
• 作为产物：
  描述：

  间苯三酚 、 2,4-dimethyl-3-hydroxymethyl-4,5-dihydrofuran 在 三氟化硼乙醚 、 magnesium sulfate 作用下， 以 乙醚 为溶剂， 以93%的产率得到xyloketal B
  参考文献：
  名称：

  Design and Synthesis of Novel Xyloketal Derivatives and Their Vasorelaxing Activities in Rat Thoracic Aorta and Angiogenic Activities in Zebrafish Angiogenesis Screen

  摘要：

  A novel series of xyloketal derivatives (1-21) were designed and prepared. The majority of the compounds demonstrated vasorelaxation action on 60 mM KCl-induced contractions rat isolated aortic rings in a concentration-dependent manner, and the action is mediated by both endothelium-independent and endothelium-dependent mechanisms. Compounds 9, 12, 13, 14, 15, and 19 showed higher vasorelaxation activities comparing with the lead compound 3. In addition, these derivatives had potential protective action against oxLDL-induced endothelial oxidative injury and enhanced NO production in HUVECs without toxic effects. The NO release was completely inhibited by eNOS inhibitor L-NAME. Furthermore, 3 significantly promoted the angiogenesis in zebrafish in a concentration-dependent manner at 0.1, 1, and 10 mu M. Compounds 9, 12, 14, 16, 20, and 21 exhibited stronger angiogenic activities than 3. Therefore, xyloketal derivatives are unique compounds with multiple pharmacological properties and may have potential implications in the treatment of cardiovascular diseases.

  DOI：

  10.1021/jm1001502

文献信息

• Design and Synthesis of Novel Xyloketal Derivatives and Their Protective Activities against H2O2-Induced HUVEC Injury
  作者：Shixin Liu、Rong Luo、Qi Xiang、Xianfang Xu、Liqin Qiu、Jiyan Pang

  DOI：10.3390/md13020948

  日期：——

  In this work, we designed and synthesized a series of amide derivatives (1–13), benzoxazine derivatives (16–28) and amino derivatives (29–30) from xyloketal B. All 28 new derivatives and seven known compounds (14, 15, 31–35) were evaluated for their protection against H2O2-induced HUVEC injury. 23 and 24 exhibited more potential protective activities than other derivatives; and the EC50 values of them and the leading compound 31 (xyloketal B) were 5.10, 3.59 and 15.97 μM, respectively. Meanwhile, a comparative molecular similarity indices analysis (CoMSIA) was constructed to explain the structural activity relationship of these xyloketal derivatives. This 3D QSAR model from CoMSIA suggested that the derived model exhibited good predictive ability in the external test-set validation. Derivative 24 fit well with the COMSIA map, therefore it possessed the highest activity of all compounds. Compounds 23, 24 and 31 (xyloketal B) were further to examine in the JC-1 mitochondrial membrane potential (MMP) assay of HUVECs using flow cytometry (FCM). The result indicated that 23 and 24 significantly inhibited H2O2-induced decrease of the cell mitochondrial membrane potential (ΔΨm) at 25 μM. Collectively, the protective effects of xyloketals on H2O2-induced endothelial cells may be generated from oxidation action by restraining ROS and reducing the MMP.

  在这项工作中，我们设计并合成了从木梨甲酯B出发的一系列酰胺衍生物（1-13）、苯并恶嗪衍生物（16-28）和氨基衍生物（29-30）。所有28个新衍生物和七个已知化合物（14，15，31-35）都被评估了它们对H2O2诱导的HUVEC损伤的保护作用。23和24表现出比其他衍生物更高的保护活性；它们的EC50值分别为5.10、3.59和15.97μM。同时，我们构建了一个比较分子相似性指数分析（CoMSIA）来解释这些木梨甲酯衍生物的结构活性关系。这个3D QSAR模型来自CoMSIA，表明推导出的模型在外部测试集验证中显示出良好的预测能力。衍生物24很好地符合CoMSIA图，因此它的活性最高。化合物23、24和31（木梨甲酯B）进一步在JC-1线粒体膜电位（MMP）分析中使用流式细胞术（FCM）对HUVECs进行检测。结果表明，23和24在25μM下显著抑制了H2O2诱导的细胞线粒体膜电位（ΔΨm）的降低。总体而言，木梨甲酯对H2O2诱导的血管内皮细胞的保护作用可能来自通过抑制ROS和减少MMP的氧化作用。
• Design and Synthesis of Novel Xyloketal Derivatives and Their Vasorelaxing Activities in Rat Thoracic Aorta and Angiogenic Activities in Zebrafish Angiogenesis Screen
  作者：Zhongliang Xu、Yiying Li、Qi Xiang、Zhong Pei、Xilin Liu、Bingtai Lu、Ling Chen、Guanlei Wang、Jiyan Pang、Yongcheng Lin

  DOI：10.1021/jm1001502

  日期：2010.6.24

  A novel series of xyloketal derivatives (1-21) were designed and prepared. The majority of the compounds demonstrated vasorelaxation action on 60 mM KCl-induced contractions rat isolated aortic rings in a concentration-dependent manner, and the action is mediated by both endothelium-independent and endothelium-dependent mechanisms. Compounds 9, 12, 13, 14, 15, and 19 showed higher vasorelaxation activities comparing with the lead compound 3. In addition, these derivatives had potential protective action against oxLDL-induced endothelial oxidative injury and enhanced NO production in HUVECs without toxic effects. The NO release was completely inhibited by eNOS inhibitor L-NAME. Furthermore, 3 significantly promoted the angiogenesis in zebrafish in a concentration-dependent manner at 0.1, 1, and 10 mu M. Compounds 9, 12, 14, 16, 20, and 21 exhibited stronger angiogenic activities than 3. Therefore, xyloketal derivatives are unique compounds with multiple pharmacological properties and may have potential implications in the treatment of cardiovascular diseases.