2-Methyl-2,6-dihydropyrano[3,2-c]quinolin-5-one | 380537-78-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-Methyl-2,6-dihydropyrano[3,2-c]quinolin-5-one
• 英文别名: 2-methyl-2H-pyrano[3,2-c]quinolin-5(6H)-one；2-Methyl-5-hydroxypyrano[3,2-c]quinoline
• CAS: 380537-78-0
• 化学式: C₁₃H₁₁NO₂
• 分子量: 213.236
• InChiKey: ZZFZLMUQYROCKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,2,3-三甲氧基-5-((E)-丙-1-烯基)苯 、 2-Methyl-2,6-dihydropyrano[3,2-c]quinolin-5-one 以 neat (no solvent) 为溶剂， 反应 16.0h， 生成 (1RS,2RS,2aRS,10aSR)-1,10-dimethyl-2-(3,4,5-trimethoxyphenyl)-1,2,2a,4,10,10a-hexahydro-3H-cyclobuta[4,5]pyrano[3,2-c]quinolin-3-one
  参考文献：
  名称：

  Euodenine A: A Small-Molecule Agonist of Human TLR4

  摘要：

  A small-molecule natural product, euodenine A (1), was identified as an agonist of the human TLR4 receptor. Euodenine A was isolated from the leaves of Euodia asteridula (Rutaceae) found in Papua New Guinea and has an unusual U-shaped structure. It was synthesized along with a series of analogues that exhibit potent and selective agonism of the TLR4 receptor. SAR development around the cyclobutane ring resulted in a 10-fold increase in potency. The natural product demonstrated an extracellular site of action, which requires the extracellular domain of TLR4 to stimulate a NF-kappa B reporter response. 1 is a human-selective agonist that is CD14-independent, and it requires both TLR4 and MD-2 for full efficacy. Testing for immunomodulation in PBMC cells shows the induction of the cytokines IL-8, IL-10, TNF-alpha, and IL-12p40 as well as suppression of IL-5 from activated PBMCs, indicating that compounds like 1 could modulate the Th2 immune response without causing lung damage.

  DOI：

  10.1021/jm401321v
• 作为产物：
  描述：

  2,4-喹啉二醇 、 丁烯-2-醛 在 ytterbium(III) triflate 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以18%的产率得到2-Methyl-2,6-dihydropyrano[3,2-c]quinolin-5-one
  参考文献：
  名称：

  Euodenine A: A Small-Molecule Agonist of Human TLR4

  摘要：

  A small-molecule natural product, euodenine A (1), was identified as an agonist of the human TLR4 receptor. Euodenine A was isolated from the leaves of Euodia asteridula (Rutaceae) found in Papua New Guinea and has an unusual U-shaped structure. It was synthesized along with a series of analogues that exhibit potent and selective agonism of the TLR4 receptor. SAR development around the cyclobutane ring resulted in a 10-fold increase in potency. The natural product demonstrated an extracellular site of action, which requires the extracellular domain of TLR4 to stimulate a NF-kappa B reporter response. 1 is a human-selective agonist that is CD14-independent, and it requires both TLR4 and MD-2 for full efficacy. Testing for immunomodulation in PBMC cells shows the induction of the cytokines IL-8, IL-10, TNF-alpha, and IL-12p40 as well as suppression of IL-5 from activated PBMCs, indicating that compounds like 1 could modulate the Th2 immune response without causing lung damage.

  DOI：

  10.1021/jm401321v

文献信息

• One-Pot Preparation of Pyranoquinolinones by Ytterbium(III) Trifluoromethanesulfonate-Catalyzed Reactions: Efficient Synthesis of Flindersine, N-Methylflindersine, and Zanthosimuline Natural Products
  作者：Yong Rok Lee、Hyuk Il Kweon、Wha Soo Koh、Kyung Rak Min、Youngsoo Kim、Seung Ho Lee

  DOI：10.1055/s-2001-17516

  日期：——

  An efficient synthesis of pyranoquinolinones is achieved by ytterbium(III) triflate-catalyzed reaction of 4-hydroxy-2-quinolones with a variety of α,β-unsaturated aldehydes in moderate yields. This new method has been applied to the synthesis of pyranoquinolinone alkaloids.

  通过铒(III)三氟乙酸盐催化4-羟基-2-吡啶酮与多种α,β-不饱和醛反应，成功合成了吡喃喹啉酮，产率适中。这种新方法已应用于吡喃喹啉酮生物碱的合成。
• Efficient Synthesis of Substituted Pyranoquinolinones from 2,4-Dihydroxy­quinoline: Total Synthesis of Zanthosimuline, <b><i>cis</i></b>-3<b>′</b>,4<b>′</b>-Dihydroxy-3<b>′</b>,4<b>′</b>-di­hydroflindersine, and Orixalone D
  作者：Yong Lee、Xue Wang

  DOI：10.1055/s-2007-983893

  日期：2007.10

  A convenient and efficient synthesis of pyranoquinoli-nones was achieved using the ethylenediamine diacetate catalyzed reactions of 2,4-dihydroxyquinoline and a variety of α,β-unsaturated aldehydes in good yield. The key feature of these reactions is the formal [3+3] cycloaddition. This new methodology was applied successfully to the total synthesis of naturally occurring pyranoquinolinone alkaloids

  使用乙二胺二乙酸酯催化的 2,4-二羟基喹啉和多种 α,β-不饱和醛的反应以良好的收率实现了一种方便高效的吡喃喹啉酮合成。这些反应的关键特征是正式的 [3+3] 环加成。这种新方法成功地应用于天然存在的吡喃喹啉酮生物碱、zanthosimuline、CIS-3',4'-dihydroxy-3',4'-dihydroflindersine 和 orixalone D 的全合成。
• Euodenine A: A Small-Molecule Agonist of Human TLR4
  作者：Juliette E. Neve、Hasanthi P. Wijesekera、Sandra Duffy、Ian D. Jenkins、Justin A. Ripper、Simon J. Teague、Marc Campitelli、Agatha Garavelas、George Nikolakopoulos、Phuc V. Le、Priscila de A. Leone、Ngoc B. Pham、Philip Shelton、Neil Fraser、Anthony R. Carroll、Vicky M. Avery、Christopher McCrae、Nicola Williams、Ronald J. Quinn

  DOI：10.1021/jm401321v

  日期：2014.2.27

  A small-molecule natural product, euodenine A (1), was identified as an agonist of the human TLR4 receptor. Euodenine A was isolated from the leaves of Euodia asteridula (Rutaceae) found in Papua New Guinea and has an unusual U-shaped structure. It was synthesized along with a series of analogues that exhibit potent and selective agonism of the TLR4 receptor. SAR development around the cyclobutane ring resulted in a 10-fold increase in potency. The natural product demonstrated an extracellular site of action, which requires the extracellular domain of TLR4 to stimulate a NF-kappa B reporter response. 1 is a human-selective agonist that is CD14-independent, and it requires both TLR4 and MD-2 for full efficacy. Testing for immunomodulation in PBMC cells shows the induction of the cytokines IL-8, IL-10, TNF-alpha, and IL-12p40 as well as suppression of IL-5 from activated PBMCs, indicating that compounds like 1 could modulate the Th2 immune response without causing lung damage.