N-乙酰基-S-(3-羟基丙基)半胱氨酸 | 23127-40-4

• 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-(3-羟基丙基)半胱氨酸
• 中文别名: 乙酰半胱氨酸杂质9钠盐
• 英文名称: N-acetyl-3-hydroxypropylmercapturic acid
• 英文别名: N-acetyl-S-(3-hydroxypropyl)-L-cysteine；S-(3-hydroxypropyl)-N-acetyl-L-cysteine；3-(N-acetyl-L-cystein-S-yl)propan-1-ol；(R)-(3-hydroxypropyl)mercapturic acid；N-acetyl-S-propanol-L-cysteine；3HPMA；N-Acetyl-S-(3-hydroxypropyl)cysteine；(2R)-2-acetamido-3-(3-hydroxypropylsulfanyl)propanoic acid
• CAS: 23127-40-4
• 化学式: C₈H₁₅NO₄S
• 分子量: 221.277
• InChiKey: FMWPQZPFBAHHMB-ZETCQYMHSA-N

物化性质

• 沸点：
  493.9±45.0 °C(Predicted)
• 密度：
  1.278±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于二甲基亚砜、甲醇、水

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 海关编码：
  2930909090

反应信息

• 作为反应物：
  描述：

  N-乙酰基-S-(3-羟基丙基)半胱氨酸 反应 0.5h， 以2%的产率得到丙烯醛
  参考文献：
  名称：

  Acrolein Mercapturates: Synthesis, Characterization, and Assessment of Their Role in the Bladder Toxicity of Cyclophosphamide

  摘要：

  Acrolein is the metabolite of cyclophosphamide (CP) believed to be involved in the bladder toxicity associated with this anticancer drug. The mechanism by which this extremely reactive intermediate is delivered to the bladder is not known. Glutathione (GSH) readily conjugates with acrolein, and the acrolein mercapturate S-(3-hydroxypropyl)-N-acetylcysteine (3-hydroxy-PrMCA) has been found in the urine of animals and man given CP. The objectives of this study were to prepare and characterize synthetic standards of the GSH acrolein adduct (3-oxopropyl)glutathione (3-oxoPrGSH), the acrolein mercapturates S-(3-oxopropyl)-N-acetylcysteine (S-oxoPrMCA) and 3-hydroxyPrMCA, and the S-oxidation product of 3-oxoPrMCA (3-oxoPrMCA S-oxide). In addition, the release of acrolein from, and the bladder toxicity of, these conjugates was determined. 3-OxoPrGSH and 3-oxoPrMCA were prepared with a 99% yield by condensing acrolein with GSH and N-acetylcysteine, respectively. 3-HydroxyPrMCA was prepared with a 63% yield by refluxing 3-chloropropanol and N-acetylcysteine in a basic medium. Oxidation of 3-oxoPrMCA with H2O2 was used to prepare 3-oxoPrMCA S-oxide. By decreasing the reaction time to 1 h, and adjusting the ratio of S-oxoPrMCA to H2O2, the yield of 3-oxoPrMCA S-oxide was increased to 96%. The anhydrous aldehyde, 3-oxoPrMCA, afforded characteristic aldehydic proton resonances (H-1 NMR) in deuterated dimethyl sulfoxide. New resonances were observed in deuterated water, indicating a 75% hydration of the aldehyde to the corresponding geminal diol. This phenomenon was enhanced with 3-oxoPrMCA S-oxide where similar to 100% hydration of the aldehyde to the corresponding geminal diol was observed. When incubated at 25 degrees C in 100 mM potassium phosphate buffer containing 1 M KCl, pH 8.0, 3-oxoPrMCA released similar to 6% and 3-oxoPrMCA S-oxide released similar to 16-18% of the theoretical maximum yield of acrolein after 30 min, as indicated by an increase in absorbance at 210 nm and confirmed by trapping this aldehyde as a semicarbazone. There was less than a 2% yield of acrolein from 3-hydroxyPrMCA or 3-oxoPrGSH under similar conditions. At pH 7.4 the release of acrolein from 3-oxoPrMCA and S-oxoPrMCA S-oxide was decreased by 50%. An assay where aldehydes are reacted with m-aminophenol in acid media produced fluorescence consistent with 72%, 46%, 23%, and 1% yields of acrolein from 3-oxoPrMCA S-oxide, 3-oxoPrMCA, 3-oxoPrGSH, and 3-hydroxyPrMCA, respectively. These yields were unaffected by incubation in buffer for up to 2 h. Acrolein, 3-oxoPrMCA S-oxide, S-oxoPrMCA and 3-oxoPrGSH, but not 3-hydroxyPrMCA, damaged the bladder dose-dependently when instilled intravesically in mice at concentrations of 10-20 mM. Potency was acrolein > 3-oxoPrMCA S-oxide > 3-oxoPrMCA > 3-oxoPrGSH. These data support the possibility that a mercapturic acid may be involved in the bladder toxicity of CP.

  DOI：

  10.1021/tx00046a005
• 作为产物：
  描述：

  N-乙酰-L-半胱氨酸 、 3-氯-1-丙醇 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以63%的产率得到N-乙酰基-S-(3-羟基丙基)半胱氨酸
  参考文献：
  名称：

  Acrolein Mercapturates: Synthesis, Characterization, and Assessment of Their Role in the Bladder Toxicity of Cyclophosphamide

  摘要：

  Acrolein is the metabolite of cyclophosphamide (CP) believed to be involved in the bladder toxicity associated with this anticancer drug. The mechanism by which this extremely reactive intermediate is delivered to the bladder is not known. Glutathione (GSH) readily conjugates with acrolein, and the acrolein mercapturate S-(3-hydroxypropyl)-N-acetylcysteine (3-hydroxy-PrMCA) has been found in the urine of animals and man given CP. The objectives of this study were to prepare and characterize synthetic standards of the GSH acrolein adduct (3-oxopropyl)glutathione (3-oxoPrGSH), the acrolein mercapturates S-(3-oxopropyl)-N-acetylcysteine (S-oxoPrMCA) and 3-hydroxyPrMCA, and the S-oxidation product of 3-oxoPrMCA (3-oxoPrMCA S-oxide). In addition, the release of acrolein from, and the bladder toxicity of, these conjugates was determined. 3-OxoPrGSH and 3-oxoPrMCA were prepared with a 99% yield by condensing acrolein with GSH and N-acetylcysteine, respectively. 3-HydroxyPrMCA was prepared with a 63% yield by refluxing 3-chloropropanol and N-acetylcysteine in a basic medium. Oxidation of 3-oxoPrMCA with H2O2 was used to prepare 3-oxoPrMCA S-oxide. By decreasing the reaction time to 1 h, and adjusting the ratio of S-oxoPrMCA to H2O2, the yield of 3-oxoPrMCA S-oxide was increased to 96%. The anhydrous aldehyde, 3-oxoPrMCA, afforded characteristic aldehydic proton resonances (H-1 NMR) in deuterated dimethyl sulfoxide. New resonances were observed in deuterated water, indicating a 75% hydration of the aldehyde to the corresponding geminal diol. This phenomenon was enhanced with 3-oxoPrMCA S-oxide where similar to 100% hydration of the aldehyde to the corresponding geminal diol was observed. When incubated at 25 degrees C in 100 mM potassium phosphate buffer containing 1 M KCl, pH 8.0, 3-oxoPrMCA released similar to 6% and 3-oxoPrMCA S-oxide released similar to 16-18% of the theoretical maximum yield of acrolein after 30 min, as indicated by an increase in absorbance at 210 nm and confirmed by trapping this aldehyde as a semicarbazone. There was less than a 2% yield of acrolein from 3-hydroxyPrMCA or 3-oxoPrGSH under similar conditions. At pH 7.4 the release of acrolein from 3-oxoPrMCA and S-oxoPrMCA S-oxide was decreased by 50%. An assay where aldehydes are reacted with m-aminophenol in acid media produced fluorescence consistent with 72%, 46%, 23%, and 1% yields of acrolein from 3-oxoPrMCA S-oxide, 3-oxoPrMCA, 3-oxoPrGSH, and 3-hydroxyPrMCA, respectively. These yields were unaffected by incubation in buffer for up to 2 h. Acrolein, 3-oxoPrMCA S-oxide, S-oxoPrMCA and 3-oxoPrGSH, but not 3-hydroxyPrMCA, damaged the bladder dose-dependently when instilled intravesically in mice at concentrations of 10-20 mM. Potency was acrolein > 3-oxoPrMCA S-oxide > 3-oxoPrMCA > 3-oxoPrGSH. These data support the possibility that a mercapturic acid may be involved in the bladder toxicity of CP.

  DOI：

  10.1021/tx00046a005

文献信息

• Identification of N-Acetylcysteine Conjugates of 1,2-Dibromo-3-chloropropane: Evidence for Cytochrome P450 and Glutathione Mediated Bioactivation Pathways
  作者：Gregory L. Weber、Rick C. Steenwyk、Sidney D. Nelson、Paul G. Pearson

  DOI：10.1021/tx00046a010

  日期：1995.6

  (Ib), N-acetyl-S-(3-hydroxypropyl)cysteine (IIa), and N-acetyl-S-(3-chloro-2-hydroxypropyl)-cysteine (III). Metabolites Ia, Ib, and III displayed quantitative retention of deuterium, an observation consistent with the formation of episulfonium ion intermediate(s) in their biogenesis. Mercapturate IIa retained three atoms of deuterium from D5-DBCP, and two atoms of deuterium from the dideuterio analogs

  卤代烷1,2-二溴-3-氯丙烷（DBCP）是致癌物，诱变剂，肾毒素和睾丸毒素。DBCP的N-乙酰半胱氨酸缀合物的鉴定提供了有关DBSH诱导的毒性表达中GSH介导的和细胞色素P450介导的生物活化途径的信息。通过反相HPLC纯化雄性Sprague-Dawley大鼠的DBCP，C1D2-DBCP，C2D1-DBCP，C3D2-DBCP或D5-DBCP（80 mg / kg）尿中排泄的N-乙酰半胱氨酸结合物作为其甲酯衍生物，并以快速原子轰击串联质谱为特征。这些代谢物也被转化为叔丁基二甲基甲硅烷基醚衍生物，并通过气相色谱-质谱法（GC-MS）进行分析，以促进鉴定N-乙酰基-S-（2,3-二羟丙基）半胱氨酸（Ia）（一种明显的区域异构体） Ia，2-（S-（N-乙酰基半胱氨酰基））-1,3-丙二醇（Ib），N-乙酰基-S-（3-羟丙基）半胱氨酸（IIa）和N-乙酰基-S-（3-氯-2 -羟丙基）-半
• Identification of Novel Metabolites of Butadiene Monoepoxide in Rats and Mice
  作者：Kevan A. Richardson、Melanie M. C. G. Peters、René H. J. J. J. Megens、Paul A. van Elburg、Bernard T. Golding、Peter J. Boogaard、William P. Watson、Nico J. van Sittert

  DOI：10.1021/tx970175v

  日期：1998.12.1

  Differences in the metabolism of 1,3-butadiene (Bd) in rats and mice may account for the observed species difference in carcinogenicity. Previous studies of the metabolic fate of Ed have identified epoxide formation as a key metabolic transformation which gives 1,2-epoxy-3-butene (BMO), although some evidence of aldehyde metabolites is reported. In this study, male Sprague-Dawley rats and male B6C3F1 mice received single doses of [4-C-14]BMO at 1, 5, 20, and 50 mg/kg of body weight (0.014, 0.071, 0.286, and 0.714 mmol/kg of body weight). Analysis of urinary metabolites indicated that both species preferentially metabolize BMO by direct reaction with GSH when given by ip administration. The excretion of (R)-2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene (IIa), 1-(N-acetyl-L-cystein-S-yl)-2-(S)-hydroxybut-3-ene (IIb), 1-(N-acetyl-L-cystein-S-yl)-2-(R)-hydroxybut-3-ene (IIc), and (S)-2-(N-acetyl-L-cystein-S-yl)- 1-hydroxybut-3-ene (IId) accounted for 48-64% of urinary radioactivity in rats and 46-54% in mice. The metabolites originating from the R-stereoisomer of BMO (IIc and IId) predominated over those arising from the S-stereoisomer (IIa and IIb) in both species. IIc was formed preferentially in mice and IId in rats. The corresponding mercaptoacetic acids, S-(1-hydroxybut-3-en-2-yl)mercaptoacetic acid (IIf) and S-(2-hydroxybut-3-en-1-yl)mercaptoacetic acid (IIg), were identified only in mouse urine (ca. 20% of the recovered radioactivity,, 4-(N-Acetyl-L-cystein-S-yl)- 1,2-dihydroxybutane (Ia), a metabolite derived from hydrolysis of BMO, accounted for 10-17% of the radioactivity in rat and 6-10% in mouse urine. 4-(N-Acetyl-L-cystein-S-yl)-2-hydroxybutanoic acid (1b), 3-(N-acetyl-L-cystein-S-yl)propan-1-ol (Ic), and 3-(N-acetyl-L-cystein-S-yl)propanoic acid (Id:). also derived from the hydrolysis of RR IO, were only present in the rat. Metabolites of 1,2,3,4-diepoxybutane (DEB) were not detected after administration of BMO in rat or mouse urine. This study showed both quantitative and qualitative differences in the metabolism of BMO with varying doses and between species. The data aid in the safety evaluation of Ed and contribute to the interpretation of mathematical models developed for quantitative risk assessment and extrapolation of animals to humans.
• Acrolein Mercapturates: Synthesis, Characterization, and Assessment of Their Role in the Bladder Toxicity of Cyclophosphamide
  作者：Kumar Ramu、Lucy H. Fraiser、Blain Mamiya、Tamer Ahmed、James P. Kehrer

  DOI：10.1021/tx00046a005

  日期：1995.6

  Acrolein is the metabolite of cyclophosphamide (CP) believed to be involved in the bladder toxicity associated with this anticancer drug. The mechanism by which this extremely reactive intermediate is delivered to the bladder is not known. Glutathione (GSH) readily conjugates with acrolein, and the acrolein mercapturate S-(3-hydroxypropyl)-N-acetylcysteine (3-hydroxy-PrMCA) has been found in the urine of animals and man given CP. The objectives of this study were to prepare and characterize synthetic standards of the GSH acrolein adduct (3-oxopropyl)glutathione (3-oxoPrGSH), the acrolein mercapturates S-(3-oxopropyl)-N-acetylcysteine (S-oxoPrMCA) and 3-hydroxyPrMCA, and the S-oxidation product of 3-oxoPrMCA (3-oxoPrMCA S-oxide). In addition, the release of acrolein from, and the bladder toxicity of, these conjugates was determined. 3-OxoPrGSH and 3-oxoPrMCA were prepared with a 99% yield by condensing acrolein with GSH and N-acetylcysteine, respectively. 3-HydroxyPrMCA was prepared with a 63% yield by refluxing 3-chloropropanol and N-acetylcysteine in a basic medium. Oxidation of 3-oxoPrMCA with H2O2 was used to prepare 3-oxoPrMCA S-oxide. By decreasing the reaction time to 1 h, and adjusting the ratio of S-oxoPrMCA to H2O2, the yield of 3-oxoPrMCA S-oxide was increased to 96%. The anhydrous aldehyde, 3-oxoPrMCA, afforded characteristic aldehydic proton resonances (H-1 NMR) in deuterated dimethyl sulfoxide. New resonances were observed in deuterated water, indicating a 75% hydration of the aldehyde to the corresponding geminal diol. This phenomenon was enhanced with 3-oxoPrMCA S-oxide where similar to 100% hydration of the aldehyde to the corresponding geminal diol was observed. When incubated at 25 degrees C in 100 mM potassium phosphate buffer containing 1 M KCl, pH 8.0, 3-oxoPrMCA released similar to 6% and 3-oxoPrMCA S-oxide released similar to 16-18% of the theoretical maximum yield of acrolein after 30 min, as indicated by an increase in absorbance at 210 nm and confirmed by trapping this aldehyde as a semicarbazone. There was less than a 2% yield of acrolein from 3-hydroxyPrMCA or 3-oxoPrGSH under similar conditions. At pH 7.4 the release of acrolein from 3-oxoPrMCA and S-oxoPrMCA S-oxide was decreased by 50%. An assay where aldehydes are reacted with m-aminophenol in acid media produced fluorescence consistent with 72%, 46%, 23%, and 1% yields of acrolein from 3-oxoPrMCA S-oxide, 3-oxoPrMCA, 3-oxoPrGSH, and 3-hydroxyPrMCA, respectively. These yields were unaffected by incubation in buffer for up to 2 h. Acrolein, 3-oxoPrMCA S-oxide, S-oxoPrMCA and 3-oxoPrGSH, but not 3-hydroxyPrMCA, damaged the bladder dose-dependently when instilled intravesically in mice at concentrations of 10-20 mM. Potency was acrolein > 3-oxoPrMCA S-oxide > 3-oxoPrMCA > 3-oxoPrGSH. These data support the possibility that a mercapturic acid may be involved in the bladder toxicity of CP.