2-丙基戊-2,4-二烯酸 | 90830-41-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 2-丙基戊-2,4-二烯酸
• 中文别名: 丙戊酸钠杂质16
• 英文名称: (E)-2-n-propyl-2,4-pentadienoic acid
• 英文别名: (E)-2-propylpenta-2,4-dienoic acid；(E)-2-propyl-2,4-pentadienoic acid；2-propyl-(E)-2,4-pentadienoic acid；2-(n-propyl)-(E)-2,4-pentenoic acid；2-n-propyl-4-pentadienoic acid；2(E),4-diene-valproate；2-Propyl-2,4-pentadienoic acid；(2E)-2-propylpenta-2,4-dienoic acid
• CAS: 90830-41-4
• 化学式: C₈H₁₂O₂
• 分子量: 140.182
• InChiKey: UUILWXIBBZVJDU-FNORWQNLSA-N

物化性质

• 沸点：
  256.9±9.0 °C(Predicted)
• 密度：
  0.975±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-丙基戊-2,4-二烯酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 48.0h， 生成 2-propyl-5-(N-acetylcystein-S-yl)pent-3-enoic acid
  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：

  丙戊酸钠杂质 在 sodium hydroxide 、 ethyl (Z)-2-n-propyl-2,4-pentadienoate 作用下， 反应 24.0h， 生成 2-丙基戊-2,4-二烯酸
  参考文献：
  名称：

  丙戊酸二不饱和代谢物的立体选择性合成

  摘要：

  丙戊酸（VPA）的两种二烯代谢物分别是（E）-2-n-丙基-2,4-戊二烯酸和（E）-2-（1'-丙烯基）-（E）-2-戊烯酸立体选择性地合成。在2的情况下，最后一步在位置2产生不饱和基的甲磺酸酯消除对（E）-构型是立体定向的。使用气相色谱-质谱和NMR确认每个二烯的构型，包括次要异构体，（ Z）-2-正丙基-2,4-戊二烯酸和（Z）-2-（1'-丙烯基）-（E）-2-戊烯酸。通过负化学电离GC-MS对来自VPA治疗患者血清提取物的PFB衍生物进行分析，发现二烯为四个峰，按照洗脱顺序分别对应于9、18、1和2。

  DOI：

  10.1002/jps.2600780813

文献信息

• Bioactivation of a Toxic Metabolite of Valproic Acid, (<i>E</i>)-2-Propyl-2,4-pentadienoic Acid, via Glucuronidation. LC/MS/MS Characterization of the GSH−Glucuronide Diconjugates
  作者：Wei Tang、Frank S. Abbott

  DOI：10.1021/tx950120y

  日期：1996.1.1

  of GST enzyme led to the formation of 5-GS-3-ene VPA-glucuronide I which was readily detected by LC/MS/MS, suggesting that in vivo the diconjugate may arise from the reaction of GSH with 2,4-diene VPA-glucuronide. To our knowledge, this is the first recorded instance in which glucuronide formation activates a drug to further conjugate with GSH via a Michael addition reaction.

  抗惊厥药丙戊酸的肝毒性可能与潜在反应性代谢物的形成有关，其中之一是（E）-2-丙基-2,4-戊二烯酸（（E）-2,4-二烯VPA）。该报告描述了该二烯新的GSH相关缀合物的表征。通过LC / MS / MS分析从腹膜内注射（E）-2,4-二烯VPA（100 mg / kg）的雄性Sprague-Dawley大鼠收集的胆汁样品。扫描中最初的Q1母体表明，子离子m / z 162和123可以分别来自m / z 624和480的离子。随后这些母离子的碰撞诱导解离（CID）显示了176 Da的常见中性损失，可诊断为葡糖醛酸苷。在大鼠腹腔内注射[2H7] -4-ene VPA产生的胆汁代谢产物的子离子光谱中观察到类似的176 Da中性损失，其中包含VPA部分的离子片段比未标记药物衍生的离子片段高7 amu。离子在m / z 624的CID也给出了GSH共轭物的片段特征，例如甘氨酸和谷氨酸部分的丢失。
• Valproic acid analogues and pharmaceutical composition thereof
  申请人：Abbott Slade Frank

  公开号：US20060223888A1

  公开（公告）日：2006-10-05

  Analogues of valproic acid useful in treating neuroaffective disorders including convulsions, bipolar disorder, and migraine headache are disclosed. The analogues are halide liver substituted analogues, cyclic analogues, and conjugated diene analogues of valproic acid. Pharmaceutical compositions or prodrugs containing the analogues or pharmaceutically acceptable salts thereof are disclosed. Methods of malting the compounds and treating mammals with neuroaffective disorders are also disclosed.

  本文介绍了一类与丙戊酸类似的化合物，可用于治疗神经情感障碍，包括惊厥、双相障碍和偏头痛。这些类似物是丙戊酸的卤代肝脏取代类似物、环状类似物和共轭二烯类似物。本文还介绍了含有这些类似物或其药学上可接受的盐的药物组合物或前药。同时，本文还介绍了制备这些化合物和治疗患有神经情感障碍的哺乳动物的方法。
• Microorganisms and methods for the production of butadiene using acetyl-coA
  申请人：Genomatica, Inc.

  公开号：US11371063B2

  公开（公告）日：2022-06-28

  The invention provides non-naturally occurring microbial organisms containing butadiene or 2,4-pentadienoate pathways comprising at least one exogenous nucleic acid encoding a butadiene or 2,4-pentadienoate pathway enzyme expressed in a sufficient amount to produce butadiene or 2,4-pentadienoate. The organism can further contain a hydrogen synthesis pathway. The invention additionally provides methods of using such microbial organisms to produce butadiene or 2,4-pentadienoate by culturing a non-naturally occurring microbial organism containing butadiene or 2,4-pentadienoate pathways as described herein under conditions and for a sufficient period of time to produce butadiene or 2,4-pentadienoate. Hydrogen can be produced together with the production of butadiene or 2,4-pentadienoate.

  本发明提供了含有丁二烯或 2,4-戊二烯酸途径的非天然存在的微生物有机体，该有机体包含至少一种编码丁二烯或 2,4-戊二烯酸途径酶的外源核酸，其表达量足以产生丁二烯或 2,4-戊二烯酸。该生物体可进一步含有氢合成途径。本发明还提供了使用此类微生物生产丁二烯或 2,4-戊二烯酸酯的方法，具体方法是将含有本文所述丁二烯或 2,4-戊二烯酸酯途径的非天然存在的微生物有机体在一定条件下培养足够长的时间，以生产丁二烯或 2,4-戊二烯酸酯。在生产丁二烯或 2,4-戊二烯酸酯的同时还可产生氢气。
• KASSAHUN, KELEM;FARRELL, KEVIN;ZHENG, JIAOJIAO;ABBOTT, FRANK, J. CHROMATOGR. BIOMED. APPL., 527,(1990) N, C. 327-341
  作者：KASSAHUN, KELEM、FARRELL, KEVIN、ZHENG, JIAOJIAO、ABBOTT, FRANK

  DOI：——

  日期：——
• SEMMES, R. L. O.;SHEN, D. D., J. CHROMATOGR. BIOMED. APPL., 432,(1988) C. 185-197
  作者：SEMMES, R. L. O.、SHEN, D. D.

  DOI：——

  日期：——