(S)-2-phenylpropionyl-1-O-acyl glucuronide | 106623-54-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (S)-2-phenylpropionyl-1-O-acyl glucuronide
• 英文别名: (S)-2-phenylpropionic acid-1-O-glucuronide；(S)-2-phenylpropionic acid glucuronide；1-β-O-acyl (S)-α-methyl phenylacetylglucuronide；1-[(α-methyl)phenyl]acetyl-β-D-glucopyranuronic acid；O¹-((S)-2-phenyl-propionyl)-β-D-glucopyranuronic acid；O¹-((S)-2-Phenyl-propionyl)-β-D-glucopyranuronsaeure；(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[(2S)-2-phenylpropanoyl]oxyoxane-2-carboxylic acid
• CAS: 106623-54-5
• 化学式: C₁₅H₁₈O₈
• 分子量: 326.303
• InChiKey: YDYDFDAUGYHMIG-DLGVBEHWSA-N

物化性质

• 沸点：
  538.5±50.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 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)-2-phenylpropionyl-1-O-acyl glucuronide 在 3-(trimethylsilyl)propionic-2,2,3,3-d₄ acid sodium salt 作用下， 以 氘代二甲亚砜 、 water-d2 为溶剂， 生成
  参考文献：
  名称：

  一组芳酸1β- O-酰基葡萄糖醛酸苷的合成，转酰基反应动力学和计算化学† ‡

  摘要：

  许多广泛使用的非甾体抗炎药（NSAID），例如 布洛芬它们的酰基葡萄糖苷酸（AGs）被广泛代谢，这些AGs的反应性引起了有关药物安全性和毒性的重要问题。为了更好地理解这些代谢物的结构反应性，我们对一组具有不同α取代度的苯乙酸酰基葡糖醛酸苷（AG）进行了合成，结构分析和计算的酰化反应性的详细研究。选择性酰化步骤来制备所有的所需的1-（苯基）乙酰基β-d葡吡喃糖醛酸9，12，13和15为以良好的收率单1β端基异构体。用1测量它们的反应性pH 7.4缓冲液中的1 H NMR光谱：在该系统中，转酰化作用相对于水解作用占优势，同时还测定了AG的1β异构体的半衰期。半衰期从化合物9的20分钟到15小时的23小时不等。缺乏对反应性的任何显着浓度依赖性表明，其主要机理是分子内的。对AG的基态和过渡态进行了新的计算化学和建模研究。酰基迁移以寻找与动力学数据的相关性并探查酰基转移的机理细节。在计算的活化能和转

  DOI：

  10.1039/b822777b
• 作为产物：
  描述：

  benzyl 1-[(α-methyl)phenyl]acetyl-β-D-glucopyranuronate 生成 (S)-2-phenylpropionyl-1-O-acyl glucuronide
  参考文献：
  名称：

  动力学和J分辨统计总相关NMR光谱学方法，用于在复杂反应混合物中回收结构信息：在酰基葡萄糖醛酸苷分子内酰化反应中的应用。

  摘要：

  我们在这里展示了一种统计光谱方法上的新变体，用于恢复反应混合物中形成的不稳定中间体的结构信息。我们以1-β-O-酰基葡糖醛酸内酯（AG）的内部酰基迁移反应为例，该反应在1到1分钟的时间内在中性或弱碱性pH值上重排，产生一系列位置性葡糖醛酸环异构体和来自1-beta（起始材料）的alpha / beta异构体，即2-beta，2-alpha，1-alpha，3-beta，3-alpha和4-beta，4-alpha异构体以及糖苷配基和alpha -和β-葡萄糖醛酸水解产物。在合成模型药物葡糖苷酸的5.1 mM溶液中收集了多个连续的800 MHz低温探针（1）H NMR谱图（1D和2D J分辨，JRES），1-D-O-酰基（S）-α-甲基苯基乙酰基葡萄糖醛酸（MPG）在D2O中的0.1 M磷酸钠缓冲液中于pD 7.4持续18 h监测反应，该反应导致形成8个位置异构体和水解产物。随着反应的进行和

  DOI：

  10.1021/ac702614t

文献信息

• Synthesis of a series of phenylacetic acid 1-β-O-acyl glucosides and comparison of their acyl migration and hydrolysis kinetics with the corresponding acyl glucuronides
  作者：Lisa Iddon、Selena E. Richards、Caroline H. Johnson、John R. Harding、Ian D. Wilson、Jeremy K. Nicholson、John C. Lindon、Andrew V. Stachulski

  DOI：10.1039/c0ob00820f

  日期：——

  carboxylate group of the acyl glucuronides plays a part in the mechanism of the internal acyl migration. In addition, such acyl glucosides are known to be endogenous biochemicals in their own right and investigation of their acyl migration propensities is novel. Our previously described selective acylation procedure has proved highly successful for 1-β-O-acyl glucuronide synthesis and when subsequently

  我们报告了 1-β- O-酰基葡萄糖苷 的共轭 苯乙酸 （PAA），R-和 S-α-甲基-PAA 和 α，α'-二甲基-PAA，并通过NMR方法测量其转酰基和水解反应性。这些是酰基葡糖醛酸苷的类似物，其酰基转移动力学在药物不良反应中可能很重要。这项工作的目的之一是调查是否如先前所推测的那样，酰基葡糖醛酸内酯的游离羧酸盐基团是否在内部机理中起作用。酰基移民。另外，已知此类酰基葡糖苷本身就是内源性生化物质，并且对其进行了研究。酰基移民倾向是新颖的。我们先前描述的选择性酰化程序已证明在以下方面非常成功1-β- O-酰基葡糖醛酸 综合以及随后应用于 6- O-三苯甲基葡萄糖，它具有良好的收率和优异的端基异构体选择性。轻度酸解邻三苯甲基中间体以优异的产率得到所需的酰基葡糖苷，基本上具有完全的β-选择性。测量酰基葡萄糖苷通过1 H NMR光谱进行的转酰基反应动力学（仅基于pH 7.4的水性缓冲液中1-
• Robinson et al., Biochemical Journal, 1955, vol. 59, p. 153,154
  作者：Robinson et al.

  DOI：——

  日期：——
• Studies on the Chemical Reactivity of 2-Phenylpropionic Acid 1-<i>O</i>-Acyl Glucuronide and <i>S</i>-Acyl-CoA Thioester Metabolites
  作者：Chunze Li、Leslie Z. Benet、Mark P. Grillo

  DOI：10.1021/tx020013l

  日期：2002.10.1

  Chemically reactive species formed from the metabolism of carboxylic acid-containing compounds have been proposed as mediators of their toxic side-effects. Two alternative metabolic pathways known to be involved in the generation of reactive acylating metabolites of carboxylic acids are acyl glucuronidation and acyl-CoA formation. Here, we present studies with 2-phenylpropionic acid focused on evaluating the relative abilities of acyl glucuronides versus acyl-CoA derivatives to transacylate the nucleophilic cysteinyl-thiol of glutathione. Thus, synthetic 2-phenylpropionyl-S-acyl-CoA (2-PPA-SCoA) and biosynthetic 2-phenylpropionyl-1-O-acyl glucuronide (2-PPA-1-O-G) were incubated separately, and at varying concentrations (15.6-500 nM as well as at 0.1 mM), with GSH (1, 5, and 10 mM) in buffer (pH 7.4, 37 degreesC), and formation of the transacylation product, 2-phenylpropionyl-S-acyl-glutathione (2-PPA-SG), was quantified by reverse-phase HPLC and LC-MS. HPLC analysis of the products from both the reaction of 2-PPA-SCoA and 2-PPA-1-O-G with GSH showed the presence of 2-PPA-SG, which was confirmed by coelution with authentic 2-PPA-SG as well as by its LC/MS mass spectrum. The formation of 2-PPA-SG was time- and concentration-dependent with a formation rate constant of (1.9 +/- 0.2) x 10(-2) M(-1.)s(-1) from reactions of GSH with 2-PPA-SCoA, and (2.7 +/- 0.4) x 10(-4) M(-1.)s(-1) from reactions of GSH with 2-PPA-1-O-G. Therefore, the reactivity of 2-PPA-SCoA with GSH was 70 times greater than the reactivity of GSH with 2-PPA-1-O-G, which was found to acyl-migrate to less reactive isomers. Analysis of the in vitro stability of 2-PPA-SCoA and 2-PPA-1-O-G in the absence of GSH showed the CoA esters to be completely stable after 24 h, whereas the acyl glucuronides decomposed by 50% in 1.3 and 2.4 h of incubation at pH 7.4 and 37 degreesC for (R)- and (S)-2-PPA-1-O-G, respectively. In addition, studies of the reactivity of 2-PPA-SCoA with bovine serum albumin showed time- and pH-dependent covalent binding to the protein in vitro. These results support the hypothesis that xenobiotic acyl-CoA thioesters are reactive acylating species that, in addition to acyl glucuronides, may contribute to xenobiotic acid-protein adduct formation in vivo.