去甲基烟碱亚硝胺 | 80508-23-2

• 物质功能分类: 分析化学 - 标准品 - 食品和饮料标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 去甲基烟碱亚硝胺
• 中文别名: N-亚硝基降烟碱(NNN)
• 英文名称: 3-(1-nitroso-pyrrolidin-2-yl)-pyridine
• 英文别名: N’-nitrosonornicotine；N′-nitrosonornicotine；N'-nitrosonornicotine；N-nitrosonornicotine；NNN；1'-nitroso-6'-nor-nicotine；3-(1-Nitrosopyrrolidin-2-yl)pyridine
• CAS: 80508-23-2
• 化学式: C₉H₁₁N₃O
• mdl: MFCD00274581
• 分子量: 177.206
• InChiKey: XKABJYQDMJTNGQ-UHFFFAOYSA-N

物化性质

• 熔点：
  43-45°C
• 沸点：
  369.5±35.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)
• 闪点：
  9℃
• 溶解度：
  氯仿：微溶，甲醇：微溶
• 物理描述：
  Solid
• 保留指数：
  1756

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

N'-亚硝基降烟碱（NNN）是已知的N'-亚硝基降烟碱（NNN）的第三手烟雾代谢物。

N'-nitrosonornicotine (NNN) is a known thirdhand smoke metabolite of N'-Nitrosonornicotine (NNN).

来源:NORMAN Suspect List Exchange

代谢

Np-亚硝基去甲烟碱已知的人类代谢物包括Np-亚硝基去甲烟碱、N-葡萄糖苷酸。

Np-nitrosonornicotine has known human metabolites that include Np-nitrosonornicotine, N-glucuronide.

来源:NORMAN Suspect List Exchange

毒理性

• 致癌物分类

国际癌症研究机构致癌物：N'-硝基索尼金

IARC Carcinogenic Agent:N'-Nitrosonornicotine

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：1类：对人类致癌

IARC Carcinogenic Classes:Group 1: Carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第7卷补充：致癌性的总体评估：更新国际癌症研究机构专著第1至42卷，1987年；440页；ISBN 92-832-1411-0（已绝版） 第89卷：（2007年）无烟烟草和一些特定于烟草的N-亚硝胺 第100E卷：（2012年）个人习惯和室内燃烧

IARC Monographs:Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print) Volume 89: (2007) Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines Volume 100E: (2012) Personal Habits and Indoor Combustions

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：N'-硝基索尼金

IARC Carcinogenic Agent:N'-Nitrosonornicotine

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：1类：对人类致癌

IARC Carcinogenic Classes:Group 1: Carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

安全信息

• 危险品标志：
  F,T
• 安全说明：
  S16,S36/37,S45
• 危险类别码：
  R25,R40,R39/23/24/25,R23/24/25,R11
• WGK Germany：
  3
• 海关编码：
  29333990
• 危险品运输编号：
  UN2811 6.1/PG 3
• 储存条件：
  -20°C 冰箱

制备方法与用途

3-(1-亚硝异吡咯烷-2-基)吡啶是一种主要的烟草特有亚硝胺。

反应信息

• 作为反应物：
  描述：

  去甲基烟碱亚硝胺 在 sodium hydroxide 作用下， 反应 88.0h， 生成 pyridyl-N-β-D-glucopyranuronosyl-N'-nitrosonornicotinium inner salt
  参考文献：
  名称：

  烟草特有亚硝胺的吡啶-N-葡糖醛酸苷的制备。

  摘要：

  尼古丁和可替宁在人体内代谢为吡啶-N-葡萄糖醛酸。这表明致癌的尼古丁相关亚硝胺N'-亚硝基亚古丁（NNN），4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮（NNK）和4-（甲基亚硝基氨基）-1的类似代谢物通过烟草产品接触这些化合物的人也应形成-（3-吡啶基）-1-丁醇（NNAL）。我们描述了合适的吡啶-N-葡糖醛酸的合成：吡啶基-N-β-D-吡喃葡萄糖醛糖基-N'-亚硝基异烟酸内盐（NNN-N-Gluc，8），4-（甲基亚硝基氨基）-1-（3-吡啶基-N-β-D-吡喃葡萄糖醛酸）-1-丁鎓内盐（NNK-N-Gluc，9）和4-（甲基亚硝胺基）-1-（3-吡啶基-N-β-D-吡喃葡萄糖醛酸）-1 -丁醇内盐（NNAL-N-Gluc，10）。起始原料甲基2,3 由葡糖醛酸内酯分两步制备4-三-O-乙酰基-1-溴-1-脱氧-α-D-吡喃葡萄糖醛酸酯（1）。1与外消旋NNN（2），NNK（3

  DOI：

  10.1021/tx000262e
• 作为产物：
  描述：

  ethyl N-methyl-N-<4-chloro-4-(3-pyridyl)butnyl>carbamate 在 silver(I) nitrite 、 硫酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 去甲基烟碱亚硝胺
  参考文献：
  名称：

  Acheson, R. Morrin; Ferris, Michael J.; Sinclair, Neil M., Journal of the Chemical Society. Perkin transactions I, 1980, p. 579 - 585

  摘要：

  DOI：

文献信息

• A facile synthesis and application of protoporphyrin derivatives on reducing the tobacco specific N-nitroamines levels of smoke
  作者：Fei Y. Tao、Chang G. Wang、Kuo Y. Ma、Dong L. Li、Lan L. Tan、Ji Zhang、Ya Dai、Xiao Q. Yu

  DOI：10.1142/s1088424613500089

  日期：2013.4

  Two protoporphyrin derivatives were prepared by a facile method using inexpensive hemin as starting material. They were added to cigarette filters to reduce the carcinogenic tobacco specific N-nitroamines (TSNAs), especially toward NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) and NNN (N-nitrosonornicotine) for environment protection and public health. The reduction level of TSNAs was reached to 37.6% from MSS, with greater reductions when more porphyrin was included in the filter. The decrease level for NNK by protoporphyrin derivatives is more effective than NNN. The interaction between protoporphyrin derivatives and TSNAs (NNK and NNN) were investigated by fluorescence spectra and UV-visible titration. The correlation coefficients were 0.978~0.997 and the binding constants was the scope from 1.26 × 10³ to 4.04 × 10⁴. The interaction mechanisms between protoporphyrin derivatives and, NNK and NNN are possibly the co-interaction of hydrogen bond binding and strong π–π stacking.

  以廉价的hemin为起始原料，通过简便的方法制备了两种原卟啉衍生物。它们被添加到香烟过滤嘴中，以减少致癌的烟草特异性 N-亚硝胺（TSNAs），尤其是 NNK（4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮）和 NNN（N-亚硝基烟碱），从而保护环境和公众健康。与 MSS 相比，TSNAs 的减少水平达到 37.6%，当过滤器中含有更多卟啉时，减少水平更高。原卟啉衍生物对 NNK 的降低水平比 NNN 更有效。通过荧光光谱和紫外可见滴定法研究了原卟啉衍生物与 TSNA（NNK 和 NNN）之间的相互作用。结果表明，原卟啉衍生物与 TSNAs（NNK 和 NNN）的结合常数为 1.26 × 103 至 4.04 × 104，相关系数为 0.978 至 0.997。原卟啉衍生物与 NNK 和 NNN 之间的相互作用机制可能是氢键结合和强π-π堆积的共同作用。
• Selective reduction of tobacco-specific nitrosamines and related methods
  申请人：Massachusetts Institute of Technology

  公开号：US10383357B2

  公开（公告）日：2019-08-20

  Aspects of the present disclosure relate to electrochemical reduction of tobacco-specific nitrosamines (TSNAs). According to certain methods described herein, a tobacco composition containing one or more TSNAs and nicotine is contacted with a solvent to form a tobacco mixture. In some embodiments, the tobacco mixture is introduced into an electrochemical device comprising an anode and a cathode. The tobacco mixture may, in some cases, form at least part of an initial electrolyte mixture that is in physical contact with at least a portion of the anode and at least a portion of the cathode. In some instances, an electrical potential is applied between the anode and the cathode, thereby reducing one or more TSNAs in the initial electrolyte mixture and producing a reduced electrolyte mixture. In certain cases, application of the electrical potential between the anode and the cathode does not cause non-TSNA components of the tobacco mixture (e.g., nicotine) to undergo electrochemical reduction or any other chemical reaction.

  本公开的各个方面涉及烟草特异性亚硝胺（TSNAs）的电化学还原。根据本文所述的某些方法，将含有一种或多种 TSNA 和尼古丁的烟草组合物与溶剂接触以形成烟草混合物。在某些实施例中，将烟草混合物引入由阳极和阴极组成的电化学装置中。在某些情况下，烟草混合物可至少构成初始电解质混合物的一部分，该混合物与阳极的至少一部分和阴极的至少一部分发生物理接触。在某些情况下，在阳极和阴极之间施加电势，从而减少初始电解质混合物中的一种或多种 TSNA，并产生还原电解质混合物。在某些情况下，在阳极和阴极之间施加电势不会导致烟草混合物中的非 TSNA 成分（如尼古丁）发生电化学还原或任何其他化学反应。
• Metabolic .beta.-hydroxylation and N-oxidation of n'-nitrosonornicotine
  作者：Stephen S. Hecht、Chi-Hong B. Chen、Dietrich Hoffmann

  DOI：10.1021/jm00185a005

  日期：1980.11

  3'-Hydroxy-N'-nitrosonornicotine (2), 4'-hydroxy-N'-nitrosonornicotine (3), N'-nitrosonornicotine 1-N-oxide (4) were synthesized and identified as metabolites in the F-344 rat of the tobacco-specific carcinogen N'-nitrosonornicotine (1). For the synthesis of 2, myosmine (5) was converted to 3'-bromomyosmine (6). Displacement by acetate and hydrolysis gave 3'-hydroxymyosmine (7), which was reduced and nitrosated to give 2. 4'-Hydroxymyosmine (13), the precursor to 3, was prepared by ammonolysis of 1,2-epoxy-4-(N-morpholino)-4-(3-pyridyl)-4-cyanobutane (10). N'-Nitrosonornicotine 1-N-oxide (4) was prepared by m-chloroperbenzoic acid oxidation of 1. When 1 was incubated with liver microsomes from Aroclor-pretreated F-344 rats, trace amounts of 2 and 3 were produced and 4 was a major metabolite. The urine from rats treated with N'-nitrosonornicotine-2'-14C contained only trace amounts of 2 and 3, whereas 4 accounted for 6.7-9.4% of the dose.
• <i>N</i>-Nitrosation of Myosmine Yields HPB (4-Hydroxy-1-(3-pyridyl)-1-butanone) and NNN (<i>N</i>-Nitrosonornicotine)
  作者：Wolfgang Zwickenpflug

  DOI：10.1021/jf9903004

  日期：2000.2.1

  N-Nitrosonornicotine (NNN) is formed by synthetic or biological N-nitrosation of the tobacco alkaloid nornicotine. Following metabolic activation of NNN, DNA and protein adducts are formed releasing 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB), an actual biomarker to differentiate between tobacco smokers and passive smokers. NNN and HPB can be prepared in a new one step reaction by N-nitrosation of the nicotinoid myosmine which has been found not only in tobacco but also in nut products. The reaction was tested also in human gastric juice. The formation rate of NNN and HPB depends on the pH value in the reaction solutions. This is important under the aspect of myosmine uptake by humans from other biological sources and subsequent biological activation. The new reaction pathway indicates that human exposure to nicotinoid nitrosation products seems to be not restricted exclusively to tobacco.
• HECHT S. S.; CHEN CHI-HONG B.; HOFFMANN D., J. MED. CHEM., 1980, 23, NO 11, 1175-1178
  作者：HECHT S. S.、 CHEN CHI-HONG B.、 HOFFMANN D.

  DOI：——

  日期：——