3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid | 176255-04-2

• 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: 3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid
• CAS: 176255-04-2
• 化学式: C₄H₄F₄O₃
• 分子量: 176.068
• InChiKey: RQKQLDVHNRCKHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid 生成 methyl 3,3,3-trifluoro-2-(fluoromethoxy)propanoate
  参考文献：
  名称：

  Evidence for Metabolism of Fluoromethyl 2,2-Difluoro-1-(trifluoromethyl)vinyl Ether (Compound A), a Sevoflurane Degradation Product, by Cysteine Conjugate β-Lyase

  摘要：

  The volatile anesthetic sevoflurane is degraded to fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE), a potent rat nephrotoxin. In rats in vivo, FDVE undergoes glutathione conjugation and metabolism to cysteine conjugates, whose bioactivation by renal cysteine conjugate beta-lyase has been implicated by the protective effects of (aminooxy)acetic acid, an inhibitor of cysteine conjugate beta-lyase. We specifically tested the hypothesis that FDVE is metabolized via the beta-lyase pathway to yield 3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid. Urine of rats administered FDVE (0.3 mmol/kg) was extracted and derivatized with diazomethane. Headspace GC/MS analysis demonstrated a peak whose retention time and mass spectrum were identical to those of synthetic methyl 3,3,3-trifluoro-2-(fluoromethoxy)propanoate. Pretreatment of rats with (aminooxy)acetic acid significantly decreased the amount of 3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid detected in the urine of FDVE-treated animals. The F-19 NMR spectrum of urine from rats administered FDVE was consistent with the formation of 3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid, but could not be differentiated from that of FDVE mercapturates, which are also excreted in urine. These results suggest that FDVE undergoes biotransformation via the beta-lyase pathway and beta-lyase-catalyzed metabolism may mediate the nephrotoxicity of this compound.

  DOI：

  10.1021/tx9502103
• 作为产物：
  描述：

  S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine 在 磷酸吡哆醛 、 copper dichloride 作用下， 以 phosphate buffer 为溶剂， 反应 1.0h， 生成 3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid 、 2-(fluoromethoxy)-3,3,3-trifluorothiopropanoyl fluoride 、 3,3,3-Trifluoro-2-fluoromethoxy-thiopropionic acid 、 2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropanethiolate
  参考文献：
  名称：

  由2-（氟甲氧基）-1,1,3,3,3-五氟-1-丙烯（化合物A）衍生的半胱氨酸S-共轭物S- [2-（氟甲氧基）-1,1,3 ，3,3-五氟丙基] -L-半胱氨酸在吡ido醛模型系统中。

  摘要：

  2-（氟甲氧基）-1,1,3,3,3-五氟-1-丙烯（化合物A）是麻醉性七氟醚的降解产物，并在大鼠中经历半胱氨酸共轭β-裂合酶依赖的生物活化作用，以产生肾毒性代谢产物。设计本实验以鉴定在两个吡ido醛中由S- [2-（氟甲氧基）-1,1,3,3,3-五氟丙基] -L-半胱氨酸（化合物A衍生的半胱氨酸S-缀合物）形成的反应性中间体模型系统，即十六烷基三甲基铵胶束中的Cu2 + /吡rid醛和N-十二烷基吡ox醛。在模型系统中，将S- [2-（氟甲氧基）-1,1,3,3,3-五氟丙基] -L-半胱氨酸与苄基溴，五氟苄基溴，苯胺和邻苯二胺作为捕集剂一起孵育。产物通过TLC纯化，并通过19F和1H NMR光谱法以及通过GC / MS鉴定。在没有捕集剂的情况下，形成了2-（氟甲氧基）-3,3,3-三氟丙酸和3,3,3-三氟乳酸，它们是先前在生物转化研究中确定的。在化学模型中，预期的第一中间体2-（氟甲氧基）-1

  DOI：

  10.1021/tx010148b

文献信息

• Evidence for Metabolism of Fluoromethyl 2,2-Difluoro-1-(trifluoromethyl)vinyl Ether (Compound A), a Sevoflurane Degradation Product, by Cysteine Conjugate β-Lyase
  作者：Douglas K. Spracklin、Evan D. Kharasch

  DOI：10.1021/tx9502103

  日期：1996.1.1

  The volatile anesthetic sevoflurane is degraded to fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE), a potent rat nephrotoxin. In rats in vivo, FDVE undergoes glutathione conjugation and metabolism to cysteine conjugates, whose bioactivation by renal cysteine conjugate beta-lyase has been implicated by the protective effects of (aminooxy)acetic acid, an inhibitor of cysteine conjugate beta-lyase. We specifically tested the hypothesis that FDVE is metabolized via the beta-lyase pathway to yield 3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid. Urine of rats administered FDVE (0.3 mmol/kg) was extracted and derivatized with diazomethane. Headspace GC/MS analysis demonstrated a peak whose retention time and mass spectrum were identical to those of synthetic methyl 3,3,3-trifluoro-2-(fluoromethoxy)propanoate. Pretreatment of rats with (aminooxy)acetic acid significantly decreased the amount of 3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid detected in the urine of FDVE-treated animals. The F-19 NMR spectrum of urine from rats administered FDVE was consistent with the formation of 3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid, but could not be differentiated from that of FDVE mercapturates, which are also excreted in urine. These results suggest that FDVE undergoes biotransformation via the beta-lyase pathway and beta-lyase-catalyzed metabolism may mediate the nephrotoxicity of this compound.
• Reactive Intermediate Formation from the 2-(Fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (Compound A)-Derived Cysteine <i>S</i>-Conjugate <i>S</i>-[2-(Fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-<scp>l</scp>-cysteine in Pyridoxal Model Systems
  作者：Zeen Tong、M. W. Anders

  DOI：10.1021/tx010148b

  日期：2002.5.1

  degradation product of the anesthetic sevoflurane and undergoes cysteine conjugate beta-lyase-dependent bioactivation to nephrotoxic metabolites in rats. The present experiments were designed to identify reactive intermediates formed from S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine, a compound A-derived cysteine S-conjugate, in two pyridoxal model systems, namely Cu2+/pyridoxal and N-dodecylpyridoxal

  2-（氟甲氧基）-1,1,3,3,3-五氟-1-丙烯（化合物A）是麻醉性七氟醚的降解产物，并在大鼠中经历半胱氨酸共轭β-裂合酶依赖的生物活化作用，以产生肾毒性代谢产物。设计本实验以鉴定在两个吡ido醛中由S- [2-（氟甲氧基）-1,1,3,3,3-五氟丙基] -L-半胱氨酸（化合物A衍生的半胱氨酸S-缀合物）形成的反应性中间体模型系统，即十六烷基三甲基铵胶束中的Cu2 + /吡rid醛和N-十二烷基吡ox醛。在模型系统中，将S- [2-（氟甲氧基）-1,1,3,3,3-五氟丙基] -L-半胱氨酸与苄基溴，五氟苄基溴，苯胺和邻苯二胺作为捕集剂一起孵育。产物通过TLC纯化，并通过19F和1H NMR光谱法以及通过GC / MS鉴定。在没有捕集剂的情况下，形成了2-（氟甲氧基）-3,3,3-三氟丙酸和3,3,3-三氟乳酸，它们是先前在生物转化研究中确定的。在化学模型中，预期的第一中间体2-（氟甲氧基）-1