(2R)-2-乙酰氨基-3-(1-羟基丁-3-烯-2-基硫基)丙酸 | 144889-51-0

• 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: (2R)-2-乙酰氨基-3-(1-羟基丁-3-烯-2-基硫基)丙酸
• 英文名称: N-acetyl-S-(1-(hydroxymethyl)-2-propenyl)-L-cysteine
• 英文别名: [2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene]；S-(1-hydroxy-3-buten-2-yl)-N-acetyl-L-cysteine；1-Hydroxy-2-(N-acetylcysteinyl)-3-butene；(2R)-2-acetamido-3-(1-hydroxybut-3-en-2-ylsulfanyl)propanoic acid
• CAS: 144889-51-0
• 化学式: C₉H₁₅NO₄S
• 分子量: 233.288
• InChiKey: CVFXMLXLNNEEJM-MQWKRIRWSA-N

物化性质

• 溶解度：
  DMSO（少许）、甲醇（少许）、水（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 (2R)-2-乙酰氨基-3-(1-羟基丁-3-烯-2-基硫基)丙酸 生成
  参考文献：
  名称：

  Synthesis and Characterization of N-Acetyl-L-cysteine S-Conjugates of Butadiene Monoxide and Their Detection and Quantitation in Urine of Rats and Mice Given Butadiene Monoxide

  摘要：

  Butadiene monoxide (BM), a mutagen and carcinogen, is the major metabolite of 1,3-butadiene in rats and mice. Because mercapturic acids (N-acetyl-L-cysteine S-conjugates) were expected in vivo metabolites of BM, reference BM-mercapturic acids were prepared by the reaction of racemic BM with N-acetyl-L-cysteine. Four isomers were purified and characterized as diastereomeric pairs of S-(2-hydroxy-3-buten-1-yl)-N-acetyl-L-cysteine (I) and S-(1-hydroxy-3-buten-2-yl)-N-acetyl-L-cysteine (II) based on analyses by H-1 NMR, fast atom bombardment mass spectrometry, and high resolution electron impact mass spectrometry. Regioisomers I and II were identified in the urine of rats and mice administered (ip) BM based on GC/MS analyses performed after HPLC fractionation followed by esterification and silylation of the carboxyl and hydroxyl groups, respectively, and comparison of GC retention times with synthetic standards. S-(4-Hydroxy-2-buten-1-yl)-N-acetyl-L-cysteine, a rearrangement pro duct formed during chemical synthesis or storage of both I and II under acidic conditions, was not detected; no other BM metabolites were evident in urine samples using this method. When rats were given BM at a dose of 71.5 to 285 mu mol/kg, their urinary excretion of I and II within 8 h of BM administration exhibited linear relationships with the administered BM dose; the total amount of the BM dose excreted as combined I and II averaged 17 +/- 4% (mean +/- SD, n = 15). No metabolites were detected in urine samples collected between 8 and 24 h after BM dosing. Mice, which are known to be more sensitive to 1,3-butadiene carcinogenicity than rats, excreted similar amounts of mercapturic acids (26 +/- 13%) at the 285 mu mol/kg BM dose within 24 h of BM administration, however, at the 143 and 71.5 mu mol/kg BM doses, they excreted only 7 +/- 3% and 9 +/- 3% of the BM dose as mercapturic acids, respectively. Thus, the ability of the rat to excrete higher levels of BM-mercapturic acids compared to the mouse at low BM doses may partially explain the lower sensitivity of the rat to 1,3-butadiene-induced carcinogenicity. Furthermore, the BM-mercapturic acid analysis method, which has limits of detection of 25 and 40 mu M in rat and mouse urine, respectively, may be used to assess human exposure to 1,3-butadiene.

  DOI：

  10.1021/tx00043a009
• 作为产物：
  描述：

  环氧丁烯 、 N-乙酰-L-半胱氨酸 在 三乙胺 作用下， 以 水 、 丙酮 为溶剂， 反应 5.5h， 生成 1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene 、 (2R)-2-乙酰氨基-3-(1-羟基丁-3-烯-2-基硫基)丙酸
  参考文献：
  名称：

  Synthesis and Characterization of N-Acetyl-L-cysteine S-Conjugates of Butadiene Monoxide and Their Detection and Quantitation in Urine of Rats and Mice Given Butadiene Monoxide

  摘要：

  Butadiene monoxide (BM), a mutagen and carcinogen, is the major metabolite of 1,3-butadiene in rats and mice. Because mercapturic acids (N-acetyl-L-cysteine S-conjugates) were expected in vivo metabolites of BM, reference BM-mercapturic acids were prepared by the reaction of racemic BM with N-acetyl-L-cysteine. Four isomers were purified and characterized as diastereomeric pairs of S-(2-hydroxy-3-buten-1-yl)-N-acetyl-L-cysteine (I) and S-(1-hydroxy-3-buten-2-yl)-N-acetyl-L-cysteine (II) based on analyses by H-1 NMR, fast atom bombardment mass spectrometry, and high resolution electron impact mass spectrometry. Regioisomers I and II were identified in the urine of rats and mice administered (ip) BM based on GC/MS analyses performed after HPLC fractionation followed by esterification and silylation of the carboxyl and hydroxyl groups, respectively, and comparison of GC retention times with synthetic standards. S-(4-Hydroxy-2-buten-1-yl)-N-acetyl-L-cysteine, a rearrangement pro duct formed during chemical synthesis or storage of both I and II under acidic conditions, was not detected; no other BM metabolites were evident in urine samples using this method. When rats were given BM at a dose of 71.5 to 285 mu mol/kg, their urinary excretion of I and II within 8 h of BM administration exhibited linear relationships with the administered BM dose; the total amount of the BM dose excreted as combined I and II averaged 17 +/- 4% (mean +/- SD, n = 15). No metabolites were detected in urine samples collected between 8 and 24 h after BM dosing. Mice, which are known to be more sensitive to 1,3-butadiene carcinogenicity than rats, excreted similar amounts of mercapturic acids (26 +/- 13%) at the 285 mu mol/kg BM dose within 24 h of BM administration, however, at the 143 and 71.5 mu mol/kg BM doses, they excreted only 7 +/- 3% and 9 +/- 3% of the BM dose as mercapturic acids, respectively. Thus, the ability of the rat to excrete higher levels of BM-mercapturic acids compared to the mouse at low BM doses may partially explain the lower sensitivity of the rat to 1,3-butadiene-induced carcinogenicity. Furthermore, the BM-mercapturic acid analysis method, which has limits of detection of 25 and 40 mu M in rat and mouse urine, respectively, may be used to assess human exposure to 1,3-butadiene.

  DOI：

  10.1021/tx00043a009

文献信息

• Synthesis and Characterization of N-Acetyl-L-cysteine S-Conjugates of Butadiene Monoxide and Their Detection and Quantitation in Urine of Rats and Mice Given Butadiene Monoxide
  作者：Adnan A. Elfarra、Jane E. Sharer、Renee J. Duescher

  DOI：10.1021/tx00043a009

  日期：1995.1

  Butadiene monoxide (BM), a mutagen and carcinogen, is the major metabolite of 1,3-butadiene in rats and mice. Because mercapturic acids (N-acetyl-L-cysteine S-conjugates) were expected in vivo metabolites of BM, reference BM-mercapturic acids were prepared by the reaction of racemic BM with N-acetyl-L-cysteine. Four isomers were purified and characterized as diastereomeric pairs of S-(2-hydroxy-3-buten-1-yl)-N-acetyl-L-cysteine (I) and S-(1-hydroxy-3-buten-2-yl)-N-acetyl-L-cysteine (II) based on analyses by H-1 NMR, fast atom bombardment mass spectrometry, and high resolution electron impact mass spectrometry. Regioisomers I and II were identified in the urine of rats and mice administered (ip) BM based on GC/MS analyses performed after HPLC fractionation followed by esterification and silylation of the carboxyl and hydroxyl groups, respectively, and comparison of GC retention times with synthetic standards. S-(4-Hydroxy-2-buten-1-yl)-N-acetyl-L-cysteine, a rearrangement pro duct formed during chemical synthesis or storage of both I and II under acidic conditions, was not detected; no other BM metabolites were evident in urine samples using this method. When rats were given BM at a dose of 71.5 to 285 mu mol/kg, their urinary excretion of I and II within 8 h of BM administration exhibited linear relationships with the administered BM dose; the total amount of the BM dose excreted as combined I and II averaged 17 +/- 4% (mean +/- SD, n = 15). No metabolites were detected in urine samples collected between 8 and 24 h after BM dosing. Mice, which are known to be more sensitive to 1,3-butadiene carcinogenicity than rats, excreted similar amounts of mercapturic acids (26 +/- 13%) at the 285 mu mol/kg BM dose within 24 h of BM administration, however, at the 143 and 71.5 mu mol/kg BM doses, they excreted only 7 +/- 3% and 9 +/- 3% of the BM dose as mercapturic acids, respectively. Thus, the ability of the rat to excrete higher levels of BM-mercapturic acids compared to the mouse at low BM doses may partially explain the lower sensitivity of the rat to 1,3-butadiene-induced carcinogenicity. Furthermore, the BM-mercapturic acid analysis method, which has limits of detection of 25 and 40 mu M in rat and mouse urine, respectively, may be used to assess human exposure to 1,3-butadiene.