2-Oxiranylmethyl-pentanoic acid ethyl ester | 102273-17-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-Oxiranylmethyl-pentanoic acid ethyl ester
• CAS: 102273-17-6
• 化学式: C₁₀H₁₈O₃
• 分子量: 186.251
• InChiKey: VNTOETHMXYSEER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.75
• 重原子数：
  13.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  38.83
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  N-乙酰-L-半胱氨酸 、 2-Oxiranylmethyl-pentanoic acid ethyl ester 以 水 、 乙腈 为溶剂， 反应 24.0h， 生成 2-propyl-5-(N-acetylcystein-S-yl)-4-hydroxypentanoic acid lactone
  参考文献：
  名称：

  Characterization of Thiol-conjugated Metabolites of 2-Propylpent-4-enoic Acid (4-eneVPA), a Toxic Metabolite of Valproic Acid, by Electrospray Tandem Mass Spectrometry

  摘要：

  The hepatotoxicity of the anticonvulsant drug valproic acid (VPA) is most likely associated with the bioactivation of its metabolite 2-propylpent-4-enoic acid (4-ene VPA), which is known to induce hepatic microvesicular steatosis in rats. This paper presents an on-line liquid chromatographic/tandem mass spectrometric (LC/MS/MS) identification of new glutathione (GSH)-related conjugates of the reactive metabolites of 4-ene VPA. Bile samples collected from male Sprague-Dawley rats dosed intraperitoneally with 4-ene VPA or its [2H7]-analogue (100 mg kg-1) were injected on to an ODS column interfaced to a LC/MS/MS instrument using electrospray ionization. LC was developed such that no overlapping of peaks occurred among those metabolites which may potentially produce common fragment ions of interest. Subsequent comparison of LC retention times and MS/MS full fragment ion spectra generated for putative metabolites with that of authentic reference compounds made available by chemical synthesis confirmed the presence of the GSH, cysteinylglycine, cysteine and N-acetylcysteine (NAC) conjugates of 2-(2'-carboxypentanyl)oxirane (4,5-epoxy VPA) and (E)-2-propylpenta-2,4-dienoic acid ((E)-2,4-diene VPA), respectively. Quantitatively, the biliary thiol conjugates accounted for 5% of the dose. This observation is novel for 4-ene VPA metabolism in terms of the degradation of GSH conjugates to the corresponding mercapturic acids possibly occurring within the liver as opposed to an inter-organ process which involves the kidney. In addition, the GSH- and NAC-glucuronide di-conjugates of (E)-2,4-diene VPA were also identified as the biliary metabolites with the GSH-glucuronide di-conjugate being 10% of the corresponding mono-GSH conjugate. Taken together, these data clearly indicate that reactive metabolites of VPA can react with hepatic GSH via several different metabolic pathways and may subsequently produce depletion of GSH that leads to toxic consequences.

  DOI：

  10.1002/(sici)1096-9888(199608)31:8<926::aid-jms383>3.0.co;2-p
• 作为产物：
  描述：

  乙基2-丙基-4-戊烯酸酯 在 二甲基二环氧乙烷 作用下， 以 丙酮 为溶剂， 反应 18.0h， 生成 2-Oxiranylmethyl-pentanoic acid ethyl ester
  参考文献：
  名称：

  Characterization of Thiol-conjugated Metabolites of 2-Propylpent-4-enoic Acid (4-eneVPA), a Toxic Metabolite of Valproic Acid, by Electrospray Tandem Mass Spectrometry

  摘要：

  The hepatotoxicity of the anticonvulsant drug valproic acid (VPA) is most likely associated with the bioactivation of its metabolite 2-propylpent-4-enoic acid (4-ene VPA), which is known to induce hepatic microvesicular steatosis in rats. This paper presents an on-line liquid chromatographic/tandem mass spectrometric (LC/MS/MS) identification of new glutathione (GSH)-related conjugates of the reactive metabolites of 4-ene VPA. Bile samples collected from male Sprague-Dawley rats dosed intraperitoneally with 4-ene VPA or its [2H7]-analogue (100 mg kg-1) were injected on to an ODS column interfaced to a LC/MS/MS instrument using electrospray ionization. LC was developed such that no overlapping of peaks occurred among those metabolites which may potentially produce common fragment ions of interest. Subsequent comparison of LC retention times and MS/MS full fragment ion spectra generated for putative metabolites with that of authentic reference compounds made available by chemical synthesis confirmed the presence of the GSH, cysteinylglycine, cysteine and N-acetylcysteine (NAC) conjugates of 2-(2'-carboxypentanyl)oxirane (4,5-epoxy VPA) and (E)-2-propylpenta-2,4-dienoic acid ((E)-2,4-diene VPA), respectively. Quantitatively, the biliary thiol conjugates accounted for 5% of the dose. This observation is novel for 4-ene VPA metabolism in terms of the degradation of GSH conjugates to the corresponding mercapturic acids possibly occurring within the liver as opposed to an inter-organ process which involves the kidney. In addition, the GSH- and NAC-glucuronide di-conjugates of (E)-2,4-diene VPA were also identified as the biliary metabolites with the GSH-glucuronide di-conjugate being 10% of the corresponding mono-GSH conjugate. Taken together, these data clearly indicate that reactive metabolites of VPA can react with hepatic GSH via several different metabolic pathways and may subsequently produce depletion of GSH that leads to toxic consequences.

  DOI：

  10.1002/(sici)1096-9888(199608)31:8<926::aid-jms383>3.0.co;2-p