N-乙酰基-S-(5-羟基-2-戊基四氢-3-呋喃基)-L-半胱氨酸 | 146764-24-1

• 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
• 中文名称: N-乙酰基-S-(5-羟基-2-戊基四氢-3-呋喃基)-L-半胱氨酸
• 英文名称: N-acetyl-S-(tetrahydro-5-hydroxy-2-pentyl-3-furanyl)-L-cysteine
• 英文别名: 4-hydroxy Nonenal Mercapturic Acid；(2R)-2-acetamido-3-(5-hydroxy-2-pentyloxolan-3-yl)sulfanylpropanoic acid
• CAS: 146764-24-1
• 化学式: C₁₄H₂₅NO₅S
• 分子量: 319.422
• InChiKey: DEWNQQSQBYUUAE-DCNVRKPOSA-N

物化性质

• 沸点：
  576.3±50.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：50mg/mL； DMSO：50mg/mL；乙醇：50mg/mL； PBS pH 7.2：0.1 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-乙酰基-S-(5-羟基-2-戊基四氢-3-呋喃基)-L-半胱氨酸 在 sodium tetrahydroborate 作用下， 生成 1,4-Dihydroxynonene mercapturic acid
  参考文献：
  名称：

  Mercapturic Acid Conjugates as Urinary End Metabolites of the Lipid Peroxidation Product 4-Hydroxy-2-nonenal in the Rat

  摘要：

  4-Hydroxy-2-nonenal (HNE), an aldehyde end product of lipid peroxidation in biological systems, is capable of producing a range of powerful biological effects. Despite its biological relevance, the metabolic fate of this aldehyde is unknown in vivo. This study examines the urinary excretion of HNE in the rat and the nature of metabolites formed. Following iv administration of [H-3]HNE, the majority of the dose appeared in urine (67.1% after 48 h). The radio-HPLC metabolic profile showed that no unchanged parent compound was detected in urine whereas at least four metabolites were present, most of them corresponding to mercapturic acid conjugates. Two major pathways were involved in the biotransformation of HNE in vivo: (i) reduction/oxidation of the aldehyde group, and (ii) conjugation to endogenous glutathione leading to mercapturic acid conjugates in urine. These end products were isolated by HPLC and identified by mass spectrometry as HNE mercapturic acid, 1,4-dihydroxynonene mercapturic acid, 4-hydroxynonenoic mercapturic acid, and the corresponding lactone.

  DOI：

  10.1021/tx00043a004
• 作为产物：
  描述：

  N-乙酰-L-半胱氨酸 、 4-羟基-2,3-壬烯醛 在 ammonium bicarbonate 作用下， 以 水 为溶剂， 反应 72.0h， 生成 N-乙酰基-S-(5-羟基-2-戊基四氢-3-呋喃基)-L-半胱氨酸
  参考文献：
  名称：

  Mercapturic Acid Conjugates as Urinary End Metabolites of the Lipid Peroxidation Product 4-Hydroxy-2-nonenal in the Rat

  摘要：

  4-Hydroxy-2-nonenal (HNE), an aldehyde end product of lipid peroxidation in biological systems, is capable of producing a range of powerful biological effects. Despite its biological relevance, the metabolic fate of this aldehyde is unknown in vivo. This study examines the urinary excretion of HNE in the rat and the nature of metabolites formed. Following iv administration of [H-3]HNE, the majority of the dose appeared in urine (67.1% after 48 h). The radio-HPLC metabolic profile showed that no unchanged parent compound was detected in urine whereas at least four metabolites were present, most of them corresponding to mercapturic acid conjugates. Two major pathways were involved in the biotransformation of HNE in vivo: (i) reduction/oxidation of the aldehyde group, and (ii) conjugation to endogenous glutathione leading to mercapturic acid conjugates in urine. These end products were isolated by HPLC and identified by mass spectrometry as HNE mercapturic acid, 1,4-dihydroxynonene mercapturic acid, 4-hydroxynonenoic mercapturic acid, and the corresponding lactone.

  DOI：

  10.1021/tx00043a004

文献信息

• Identification of Intermediate Pathways of 4-Hydroxynonenal Metabolism in the Rat
  作者：Jacques Alary、Yvette Fernandez、Laurent Debrauwer、Elisabeth Perdu、Françoise Guéraud

  DOI：10.1021/tx025671k

  日期：2003.3.1

  The formation of 4-hydroxy-2-nonenal (HNE) conjugates with glutathione (GSH) by Michael addition and subsequent cleavage to yield the related mercapturic acid (MA) conjugates are a major detoxication process. To characterize the metabolic pathways involved in the formation of urinary HNE-MA conjugates in the rat, the metabolism of HNE-thioethers (HNE-GSH, HNE-MA, and HNE-Cys) by rat liver and kidney cytosolic fractions was investigated. The experimental results showed that HNE-GSH is a good substrate for cytosolic incubations whereas HNE-MA and HNE-Cys are poorly metabolized. About 80% of the urinary MA conjugates originate from the primary and major HNE metabolite, namely, the hemiacetalized HNE-GSH. The direct reduction of HNE-GSH by a cytosolic aldo-keto reductase (NADPH) leads to 1,4-dihydroxynonene-GSH (DHN-GSH) and subsequently to DHN-MA. The direct oxidation of HNE-GSH by aldehyde dehydrogenase (NAD)(+) leads to 4-hydroxynonenoiclactone-GSH, the partial hydrolysis of which occurs at physiological pH and accounts for the corresponding 4-hydroxynonenoic-GSH. Both the spontaneous- and the glutathione S-transferases-catalyzed retro-Michael cleavages of HNE-GSH and HNA-lactone-GSH are the source of HNE and HNA-lactone, respectively. This latter compound, with both lipophilic and electrophilic properties, is available for microsomal omega-hydroxylation by cytochrome P450 4A enzymes and conjugation with thiol groups and therefore is the most likely candidate for the formation of omega-hydroxylated HNE-mercapturic acid conjugates excreted in rat urine.
• Mercapturic Acid Conjugates as Urinary End Metabolites of the Lipid Peroxidation Product 4-Hydroxy-2-nonenal in the Rat
  作者：Jacques Alary、Fabienne Bravais、Jean-Pierre Cravedi、Laurent Debrauwer、Dinesh Rao、George Bories

  DOI：10.1021/tx00043a004

  日期：1995.1

  4-Hydroxy-2-nonenal (HNE), an aldehyde end product of lipid peroxidation in biological systems, is capable of producing a range of powerful biological effects. Despite its biological relevance, the metabolic fate of this aldehyde is unknown in vivo. This study examines the urinary excretion of HNE in the rat and the nature of metabolites formed. Following iv administration of [H-3]HNE, the majority of the dose appeared in urine (67.1% after 48 h). The radio-HPLC metabolic profile showed that no unchanged parent compound was detected in urine whereas at least four metabolites were present, most of them corresponding to mercapturic acid conjugates. Two major pathways were involved in the biotransformation of HNE in vivo: (i) reduction/oxidation of the aldehyde group, and (ii) conjugation to endogenous glutathione leading to mercapturic acid conjugates in urine. These end products were isolated by HPLC and identified by mass spectrometry as HNE mercapturic acid, 1,4-dihydroxynonene mercapturic acid, 4-hydroxynonenoic mercapturic acid, and the corresponding lactone.