morphine 6-glucoronide

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: morphine 6-glucoronide
• 英文别名: (2S,3S,4S,5R,6R)-6-[[(4R,4aR,7R,7aS,12bS)-9-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]oxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
• 化学式: C₂₃H₂₇NO₉
• 分子量: 461.469
• InChiKey: GNJCUHZOSOYIEC-VJXYMCLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  149
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  morphine 在 sodium methylate 、 silver carbonate 作用下， 以 甲醇 、 水 、 苯 为溶剂， 反应 0.33h， 生成 morphine 6-glucoronide
  参考文献：
  名称：

  Morphine 6-glucuronide and morphine 3-glucuronide as molecular chameleons with unexpected lipophilicity

  摘要：

  Morphine 6-glucuronide, but not morphine 3-glucuronide, is a highly potent opiate receptor agonist. In fact, there is converging evidence that much of the analgesic effect occurring after morphine treatment in humans is due to this metabolite rather than to the parent drug. Yet glucuronides as a rule are considered as highly polar metabolites unable to cross the blood-brain barrier and rapidly excreted by the urinary and/or biliary routes. Here, we report that morphine 6-glucuronide, and to a lesser extent morphine 3-glucuronide, are far more lipophilic than predicted, and in fact not much less lipophilic than morphine itself. Force-field and quantum mechanical calculations indicate that the two glucuronides can exist in conformational equilibrium between extended and folded forms. The extended conformers, because they efficiently expose their polar groups, must be highly hydrophilic forms predominating in polar media such as water; in contrast, the folded conformers mask part of their polar groups, thus being more lipophilic and likely to predominate in media of low polarity such as biological membranes.

  DOI：

  10.1021/jm00108a005

文献信息

• Morphine 6-glucuronide and morphine 3-glucuronide as molecular chameleons with unexpected lipophilicity
  作者：Pierre Alain Carrupt、Bernard Testa、Antoine Bechalany、Nabil El Tayar、Patrick Descas、Daniel Perrissoud

  DOI：10.1021/jm00108a005

  日期：1991.4

  Morphine 6-glucuronide, but not morphine 3-glucuronide, is a highly potent opiate receptor agonist. In fact, there is converging evidence that much of the analgesic effect occurring after morphine treatment in humans is due to this metabolite rather than to the parent drug. Yet glucuronides as a rule are considered as highly polar metabolites unable to cross the blood-brain barrier and rapidly excreted by the urinary and/or biliary routes. Here, we report that morphine 6-glucuronide, and to a lesser extent morphine 3-glucuronide, are far more lipophilic than predicted, and in fact not much less lipophilic than morphine itself. Force-field and quantum mechanical calculations indicate that the two glucuronides can exist in conformational equilibrium between extended and folded forms. The extended conformers, because they efficiently expose their polar groups, must be highly hydrophilic forms predominating in polar media such as water; in contrast, the folded conformers mask part of their polar groups, thus being more lipophilic and likely to predominate in media of low polarity such as biological membranes.