(2S)-5-[[(2R)-3-[2-[(1R,4aS,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-1-(5-oxo-2H-furan-4-yl)ethyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-2-amino-5-oxopentanoic acid | 1092960-37-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-5-[[(2R)-3-[2-[(1R,4aS,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-1-(5-oxo-2H-furan-4-yl)ethyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-2-amino-5-oxopentanoic acid
• CAS: 1092960-37-6
• 化学式: C₃₀H₄₅N₃O₁₀S
• 分子量: 639.767
• InChiKey: LMRMPLULFWJGSI-JANNGQBISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  44
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  251
• 氢给体数：
  7
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  谷胱甘肽 、 穿心莲内酯 以 乙醇 为溶剂， 生成 (2S)-5-[[(2R)-3-[2-[(1R,4aS,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-1-(5-oxo-2H-furan-4-yl)ethyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-2-amino-5-oxopentanoic acid 、 (2S)-2-[[2-[(1R,4aS,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-1-(5-oxo-2H-furan-4-yl)ethyl]amino]-5-[[(2R)-1-(carboxymethylamino)-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  Molecular Interaction between Andrographolide and Glutathione Follows Second Order Kinetics

  摘要：

  向 HepG2 细胞培养物中添加穿心莲内酯 (1) 后，细胞内谷胱甘肽 (GSH) 水平显着降低。当在模拟体内环境的条件下研究穿心莲内酯和 GSH 之间的分子相互作用时，我们观察到穿心莲内酯存在时 GSH 水平下降。化学计量分析表明，在pH 7 时，这两种反应物之间的反应为1:1，并且遵循二级动力学。根据阿伦尼乌斯方程，整个反应的活化能为41.9±10 kJ·mol−1。采用微液-液萃取法和胶束电动色谱分离，分离鉴定了两种主要产物，并确定其化学结构为14-脱氧-12-(谷胱甘肽-氨基)-穿心莲内酯(2)和14-脱氧-12-(谷胱甘肽-氨基)-穿心莲内酯(2)和14-脱氧-12-(谷胱甘肽-S-基)-穿心莲内酯(3)。基于这些结构发现，提出了谷胱甘肽和穿心莲内酯之间反应的假设机制。结论是穿心莲内酯的α,β-不饱和内酯部分与GSH通过迈克尔加成反应，然后加合物脱水。

  DOI：

  10.1248/cpb.56.1229

文献信息

• Molecular Interaction between Andrographolide and Glutathione Follows Second Order Kinetics
  作者：Zhiqiang Zhang、Gallant Kar-Lun Chan、Jieliang Li、Wang-Fun Fong、Hon-Yeung Cheung

  DOI：10.1248/cpb.56.1229

  日期：——

  The intracellular level of glutathione (GSH) was significantly decreased after the addition of andrographolide (1) to cell cultures of HepG2. When the molecular interaction between andrographolide and GSH was investigated under a condition mimicking the in vivo environment, we observed that the level of GSH dropped in the presence of andrographolide. Stoichiometric analysis indicates that the reaction between these two reactants was 1 to 1 at pH 7 and followed second order kinetics. The activation energy of the overall reaction was 41.9±10 kJ·mol−1 according to the Arrhenius equation. Using a micro-liquid–liquid extraction method followed by micellar electrokinetic chromatographic separation, two major products were isolated and identified, and their chemical structures were determined as 14-deoxy-12-(glutathione-amino)-andrographolide (2) and 14-deoxy-12-(glutathione-S-yl)-andrographolide (3). Based on these structural findings, a hypothetical mechanism of reaction between glutathione and andrographolide was proposed. It is concluded that the α,β-unsaturated lactone moiety of andrographolide reacts with GSH through a Michael addition followed by dehydration of the adduct.

  向 HepG2 细胞培养物中添加穿心莲内酯 (1) 后，细胞内谷胱甘肽 (GSH) 水平显着降低。当在模拟体内环境的条件下研究穿心莲内酯和 GSH 之间的分子相互作用时，我们观察到穿心莲内酯存在时 GSH 水平下降。化学计量分析表明，在pH 7 时，这两种反应物之间的反应为1:1，并且遵循二级动力学。根据阿伦尼乌斯方程，整个反应的活化能为41.9±10 kJ·mol−1。采用微液-液萃取法和胶束电动色谱分离，分离鉴定了两种主要产物，并确定其化学结构为14-脱氧-12-(谷胱甘肽-氨基)-穿心莲内酯(2)和14-脱氧-12-(谷胱甘肽-氨基)-穿心莲内酯(2)和14-脱氧-12-(谷胱甘肽-S-基)-穿心莲内酯(3)。基于这些结构发现，提出了谷胱甘肽和穿心莲内酯之间反应的假设机制。结论是穿心莲内酯的α,β-不饱和内酯部分与GSH通过迈克尔加成反应，然后加合物脱水。