1,1,1',1'-2H4-N-nitrosodiethanolamine | 57154-81-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1,1,1',1'-2H4-N-nitrosodiethanolamine
• 英文别名: α-D4-N-nitrosodiethanolamine；N-Nitroso-bis(1,1-dideuterio-2-hydroxyethyl)amin；N,N-bis(1,1-dideuterio-2-hydroxyethyl)nitrous amide
• CAS: 57154-81-1
• 化学式: C₄H₁₀N₂O₃
• 分子量: 138.103
• InChiKey: YFCDLVPYFMHRQZ-LNLMKGTHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  9
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  73.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,1,1',1'-2H4-N-nitrosodiethanolamine 在 horse liver ADH 作用下， 以 phosphate buffer 为溶剂， 反应 0.07h， 生成 N-亚硝基-2-羟基吗啉
  参考文献：
  名称：

  Probing the Mechanism of the Carcinogenic Activation of N-Nitrosodiethanolamine with Deuterium Isotope Effects:  In Vivo Induction of DNA Single-Strand Breaks and Related in Vitro Assays

  摘要：

  A series of bioassays, including in vivo induction of DNA single-strand breaks (SSB) and cytotoxicity in cytochrome P450 2E1-transfected cells, were utilized with N-nitrosodiethanolamine (NDELA), its deuterated isotopomers (alpha-D(4)NDELA and beta-D(4)NDELA), N-nitroso-2-hydroxymorpholine (NHMOR), and two of its deuterated isotopomers (2-D-NHMOR and 5,5-D-2-NHMOR) to probe the mechanism of carcinogenic activation of NDELA and the role of its metabolite NHMOR. DNA samples, taken from the livers of male Wistar rats 4 h after the administration of NDELA, exhibited dose-dependent DNA SSB levels over the range of 0.08-0.75 mmol/kg (body weight), with the greatest SSB level at the highest dose. Deuterium isotope effects on DNA SSB levels were inversely dependent on dose: alpha-D(4)NDELA, 3.22-1.37; and beta-D(4)NDELA, 1.38-0.79, At the lowest dose of 0.15 mmol/kg (body weight), 5,5-D-2-NHMOR gave an isotope effect for DNA SSB of 2.8 while that for 2-D-NHMOR was 0.7, NDELA and beta-D(4)NDELA were equally cytotoxic to human P450 2E1-transfected V79 Chinese hamster cells, while alpha-D(4)NDELA was not. Significant DNA SSR levels were observed in these cells for NDELA and beta-D(4)NDELA but not for alpha-D(4)NDELA. A kinetic deuterium isotope effect of 2.6 NDELA to NHMOR, while k(II)/k(D) for alpha-D(4)NDELA was 1.05, These data provide the first definitive evidence fur the activation of NDELA by a pathway involving the scission of the alpha-CH bond and are consistent with P450 2E1-mediated alpha-hydroxylation of NDELA producing the corresponding reactive alpha-hydroxynitrosamine.

  DOI：

  10.1021/tx9801716
• 作为产物：
  描述：

  二乙醇亚硝胺 在 氘氧化钠 、 重水 作用下， 反应 10.0h， 以82%的产率得到1,1,1',1'-2H4-N-nitrosodiethanolamine
  参考文献：
  名称：

  The synthesis of deuterium-labeled N-nitrosodiethanolamine and N-nitroso-2-hydroxymorpholine

  摘要：

  制备了两份N-亚硝基二乙醇胺的氘代衍生物和两份N-亚硝基-2-羟基吗啉的氘代衍生物。1a 1，1，1'，1'-2H4-N-亚硝基二乙醇胺以99%的同位素纯度通过简单的碱催化H-D交换反应制备得到。1b 2，2，2'，2'-2H4-N-亚硝基二乙醇胺以98%的同位素纯度通过二甲基亚氨基二乙酸酯的LiAlD4还原反应合成，随后进行酸催化硝化反应。2a 5，5-2H2-N-亚硝基-2-羟基吗啉通过一系列步骤制备，包括1)选择性碱催化H-D交换反应，涉及酯功能团邻近的CH2基团的交换，2)在-8°C下使用二异丁基氢化铝还原，3)酸催化水解原酸酯和环化成半缩醛，最终得到99%的同位素纯度。2b 2-2H-N-亚硝基-2-羟基吗啉（98%同位素纯度）是通过在-78°C下使用LiAlD4还原2-羟乙基亚氨基二乙酸酯制备的。

  DOI：

  10.1002/jlcr.2580341114

文献信息

• Loeppky Richard N., Xiong Heping, J. Labell. Compounds and Radiopharm, 34 (1994) N 11, S 1099-1110
  作者：Loeppky Richard N., Xiong Heping

  DOI：——

  日期：——
• The synthesis of deuterium-labeled N-nitrosodiethanolamine and N-nitroso-2-hydroxymorpholine
  作者：Richard N. Loeppky、Heping Xiong

  DOI：10.1002/jlcr.2580341114

  日期：1994.11

  Two deuterated derivatives of N-nitrosodiethanolamine and two deuterated derivatives of N-Nitroso-2-hydroxymorpholine were prepared. 1,1,1′,1′-2H4-N-Nitrosodiethanolamine 1a was prepared in 99% isotopic purity by simple base catalyzed H-D exchange. 2,2,2′,2′-2H4-N-Nitrosodiethanolamine 1b was synthesized in 98% isotopic purity by the LiAlD4 reduction of dimethyl iminodiethanoate, followed by acid catalyzed nitrosation. 5,5-2H2-N-Nitroso-2-hydroxymorpholine 2a was prepared in 99% isotopic purity through a series of steps involving 1) the selective base catalyzed H-D exchange of the CH2 adjacent to the ester function of 2,2-diethoxyethylcarboethoxymethylnitrosamine, 2) its reduction with diisobutylaluminum hydride at −8°C followed by 3) acid catalyzed hydrolysis of the acetal and cyclization to the hemiacetal. 2-2H-N-Nitroso-2-hydroxymorpholine 2b (98% isotopic purity) was prepared through the LiAlD4 reduction of 2-hydroxyethylcorboethoxymethylnitrosamine at −78°C.

  制备了两份N-亚硝基二乙醇胺的氘代衍生物和两份N-亚硝基-2-羟基吗啉的氘代衍生物。1a 1，1，1'，1'-2H4-N-亚硝基二乙醇胺以99%的同位素纯度通过简单的碱催化H-D交换反应制备得到。1b 2，2，2'，2'-2H4-N-亚硝基二乙醇胺以98%的同位素纯度通过二甲基亚氨基二乙酸酯的LiAlD4还原反应合成，随后进行酸催化硝化反应。2a 5，5-2H2-N-亚硝基-2-羟基吗啉通过一系列步骤制备，包括1)选择性碱催化H-D交换反应，涉及酯功能团邻近的CH2基团的交换，2)在-8°C下使用二异丁基氢化铝还原，3)酸催化水解原酸酯和环化成半缩醛，最终得到99%的同位素纯度。2b 2-2H-N-亚硝基-2-羟基吗啉（98%同位素纯度）是通过在-78°C下使用LiAlD4还原2-羟乙基亚氨基二乙酸酯制备的。
• Probing the Mechanism of the Carcinogenic Activation of <i>N</i>-Nitrosodiethanolamine with Deuterium Isotope Effects:  In Vivo Induction of DNA Single-Strand Breaks and Related in Vitro Assays
  作者：Richard N. Loeppky、Anne Fuchs、Christine Janzowski、Christina Humberd、Petra Goelzer、Heiko Schneider、Gerhard Eisenbrand

  DOI：10.1021/tx9801716

  日期：1998.12.1

  A series of bioassays, including in vivo induction of DNA single-strand breaks (SSB) and cytotoxicity in cytochrome P450 2E1-transfected cells, were utilized with N-nitrosodiethanolamine (NDELA), its deuterated isotopomers (alpha-D(4)NDELA and beta-D(4)NDELA), N-nitroso-2-hydroxymorpholine (NHMOR), and two of its deuterated isotopomers (2-D-NHMOR and 5,5-D-2-NHMOR) to probe the mechanism of carcinogenic activation of NDELA and the role of its metabolite NHMOR. DNA samples, taken from the livers of male Wistar rats 4 h after the administration of NDELA, exhibited dose-dependent DNA SSB levels over the range of 0.08-0.75 mmol/kg (body weight), with the greatest SSB level at the highest dose. Deuterium isotope effects on DNA SSB levels were inversely dependent on dose: alpha-D(4)NDELA, 3.22-1.37; and beta-D(4)NDELA, 1.38-0.79, At the lowest dose of 0.15 mmol/kg (body weight), 5,5-D-2-NHMOR gave an isotope effect for DNA SSB of 2.8 while that for 2-D-NHMOR was 0.7, NDELA and beta-D(4)NDELA were equally cytotoxic to human P450 2E1-transfected V79 Chinese hamster cells, while alpha-D(4)NDELA was not. Significant DNA SSR levels were observed in these cells for NDELA and beta-D(4)NDELA but not for alpha-D(4)NDELA. A kinetic deuterium isotope effect of 2.6 NDELA to NHMOR, while k(II)/k(D) for alpha-D(4)NDELA was 1.05, These data provide the first definitive evidence fur the activation of NDELA by a pathway involving the scission of the alpha-CH bond and are consistent with P450 2E1-mediated alpha-hydroxylation of NDELA producing the corresponding reactive alpha-hydroxynitrosamine.