(S)-布洛芬葡糖苷酸 | 98649-76-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (S)-布洛芬葡糖苷酸
• 英文名称: 1-β-O-acyl (S)-ibuprofen glucoronide
• 英文别名: S-ibuprofen glucuronide；(+)-Ibuprofen glucuronide；Dexibuprofen-acyl-b-D-glucuronide；(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[(2S)-2-[4-(2-methylpropyl)phenyl]propanoyl]oxyoxane-2-carboxylic acid
• CAS: 98649-76-4
• 化学式: C₁₉H₂₆O₈
• 分子量: 382.411
• InChiKey: ABOLXXZAJIAUGR-LEBSGKMFSA-N

物化性质

• 沸点：
  567.3±50.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-布洛芬葡糖苷酸 在 TSP 作用下， 以 phosphate buffer 、 重水 为溶剂， 生成 (S)-(+)-布洛芬
  参考文献：
  名称：

  NMR光谱研究布洛芬（（+/-）-（R，S）-2-（4-异丁基苯基）丙酸），其代谢物和类似物的体外酰基葡萄糖醛酸化物迁移动力学。

  摘要：

  含羧酸的药物通常代谢为1-β-O-酰基葡萄糖醛酸苷（AGs）。这些可以进行内部化学重排，并且所得的反应性位置异构体可以结合至内源蛋白质，具有明显的潜在不良作用。另外，药物的任何1-β-O-酰基-葡糖醛酸化的I期代谢物也都可以显示这种倾向，对药物的潜在不良反应进行研究时也需要考虑此类代谢物。在这里，对普通药物布洛芬及其两种代谢物的转酰基作用进行了体外研究。从人尿液中分离出1-β-O-酰基（S）-布洛芬葡糖醛酸，并通过选择性酰化合成。尿液还用作（R）-布洛芬，（S）-2-羟基布洛芬和（S，S）-羧基布洛芬AG的来源。使用1H NMR光谱仪测量降解速率（转酰化和水解的组合），并将测得的1-β端基异构体随时间的减少用于得出葡糖醛酸苷的半衰期。生物合成和化学合成的（S）-布洛芬AG的半衰期分别为3.68和3.76 h。（R）-布洛芬AG的半衰期为1.79小时，约为（S）-非对映异构体的一半，与其他2

  DOI：

  10.1021/ac071368i
• 作为产物：
  描述：

  (S)-(+)-布洛芬 在 palladium on activated charcoal N-甲基吗啉 、 1,4-环己二烯 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 异丙醇 、 乙腈 为溶剂， 反应 2.0h， 生成 (S)-布洛芬葡糖苷酸
  参考文献：
  名称：

  Efficient synthesis of 1β-O-acyl glucuronides via selective acylation of allyl or benzyl d-glucuronate

  摘要：

  Acyl glucuronides are key metabolites for many carboxylic acid-containing drugs, notably those of the non-steroidal anti-inflammatory class. In the processes of drug safety assessment and new drug development, it is essential that acyl glucuronides, if formed in vivo, should be made conveniently available for bioevaluation. We recently showed that selective acylation of allyl glucuronate is a promising method for the synthesis of these metabolites in good yield and with excellent beta-anomeric selectivity. We now give fuller details of the allyl ester method and further report that benzyl glucuronate performs at least equally well in the acylation step, offering the advantage of very mild deprotection by catalytic transfer (or conventional) hydrogenation. Depending on the compatibility of other functional groups, as discussed below, this will be the method of choice for many acyl glucuronide syntheses. The value of the method is demonstrated in particular by the synthesis of several acyl glucuronides that are known metabolites of important drugs. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.05.050

文献信息

• Efficient synthesis of 1β-O-acyl glucuronides via selective acylation of allyl or benzyl d-glucuronate
  作者：Elizabeth R. Bowkett、John R. Harding、James L. Maggs、B. Kevin Park、Jennifer A. Perrie、Andrew V. Stachulski

  DOI：10.1016/j.tet.2007.05.050

  日期：2007.8

  Acyl glucuronides are key metabolites for many carboxylic acid-containing drugs, notably those of the non-steroidal anti-inflammatory class. In the processes of drug safety assessment and new drug development, it is essential that acyl glucuronides, if formed in vivo, should be made conveniently available for bioevaluation. We recently showed that selective acylation of allyl glucuronate is a promising method for the synthesis of these metabolites in good yield and with excellent beta-anomeric selectivity. We now give fuller details of the allyl ester method and further report that benzyl glucuronate performs at least equally well in the acylation step, offering the advantage of very mild deprotection by catalytic transfer (or conventional) hydrogenation. Depending on the compatibility of other functional groups, as discussed below, this will be the method of choice for many acyl glucuronide syntheses. The value of the method is demonstrated in particular by the synthesis of several acyl glucuronides that are known metabolites of important drugs. (C) 2007 Elsevier Ltd. All rights reserved.
• NMR Spectroscopic Studies on the in Vitro Acyl Glucuronide Migration Kinetics of Ibuprofen ((±)-(<i>R</i>,<i>S</i>)-2-(4-Isobutylphenyl) Propanoic Acid), Its Metabolites, and Analogues
  作者：Caroline H. Johnson、Ian D. Wilson、John R. Harding、Andrew V. Stachulski、Lisa Iddon、Jeremy K. Nicholson、John C. Lindon

  DOI：10.1021/ac071368i

  日期：2007.11.1

  AGs had half-lives of 3.68 and 3.76 h, respectively. (R)-Ibuprofen AG had a half-life of 1.79 h, a value approximately half that of the (S)-diastereoisomer, consistent with results from other 2-aryl propionic acid drug AGs. The 2-hydroxyibuprofen and carboxyibuprofen AGs gave half-lives of 5.03 and 4.80 h, considerably longer than that of either of the parent drug glucuronides. In addition, two (S)-ibuprofen

  含羧酸的药物通常代谢为1-β-O-酰基葡萄糖醛酸苷（AGs）。这些可以进行内部化学重排，并且所得的反应性位置异构体可以结合至内源蛋白质，具有明显的潜在不良作用。另外，药物的任何1-β-O-酰基-葡糖醛酸化的I期代谢物也都可以显示这种倾向，对药物的潜在不良反应进行研究时也需要考虑此类代谢物。在这里，对普通药物布洛芬及其两种代谢物的转酰基作用进行了体外研究。从人尿液中分离出1-β-O-酰基（S）-布洛芬葡糖醛酸，并通过选择性酰化合成。尿液还用作（R）-布洛芬，（S）-2-羟基布洛芬和（S，S）-羧基布洛芬AG的来源。使用1H NMR光谱仪测量降解速率（转酰化和水解的组合），并将测得的1-β端基异构体随时间的减少用于得出葡糖醛酸苷的半衰期。生物合成和化学合成的（S）-布洛芬AG的半衰期分别为3.68和3.76 h。（R）-布洛芬AG的半衰期为1.79小时，约为（S）-非对映异构体的一半，与其他2