N-亚硝基肌氨酸 | 13256-22-9

• 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-亚硝基肌氨酸
• 英文名称: N-nitrososarcosine
• 英文别名: N-Nitrososarcosin；N-methyl-N-nitrosoglycine；N-Nitroso-sarkosin；2-[Methyl(nitroso)azaniumyl]acetate
• CAS: 13256-22-9
• 化学式: C₃H₆N₂O₃
• mdl: MFCD00152671
• 分子量: 118.092
• InChiKey: HJMPSKKJHVWPBK-UHFFFAOYSA-N

物化性质

• 熔点：
  66-67°C
• 沸点：
  220.6°C (rough estimate)
• 密度：
  1.5267 (rough estimate)
• 溶解度：
  DMF：15 mg/ml，DMSO：10 mg/ml，乙醇：30 mg/ml，PBS（pH 7.2）：5 mg/ml
• 颜色/状态：
  Pale-yellow crystals
• 蒸汽压力：
  2.61X10-3 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Partially decarboxylates on heating at 180-190 °C to form N-nitrosodimethylamine
• 分解：
  When heated to decomposition it emits toxic fumes of ... /nitrogen oxides/.
• 解离常数：
  pKa = 3.63 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

代谢

一种用于定量估算大鼠内源性亚硝化的简单而敏感的方法被开发出来。这种方法基于以下发现：当亚硝基氨基酸（例如，亚硝基脯氨酸（NPRO）、亚硝基羟基脯氨酸（NHPRO）和亚硝基 sarcosine（NSAR））口服给大鼠时，它们几乎定量（剂量的88-96%）未改变地通过尿液和粪便排出。在顺序给予可亚硝化氨基酸和硝酸钠后，分析了尿液中排出的亚硝基氨基酸。大鼠尿液中排出的亚硝基脯氨酸的量与脯氨酸的剂量和亚硝酸钠剂量的平方成正比。同时给予抗坏血酸和α-生育酚以及前体物质会减少尿液中亚硝基脯氨酸的排出，而硫氰酸盐会增加产量。在喂食氨基酸前体和亚硝酸盐后，形成的亚硝基氨基酸并从尿液中排出的产量按以下顺序增加：亚硝基脯氨酸 < 亚硝基 sarcosine < 亚硝基羟基脯氨酸。当比较氨基酸在体外亚硝化的速率时，也观察到了相同的顺序。显然，大鼠体内的亚硝化作用通过一种与体外观察到的机制相似的机制发生。监测尿液中排出的亚硝基氨基酸似乎为内源性亚硝化提供了一个有价值的指标...

A simple and sensitive method for the quantitative estimation of endogenous N-nitrosation in rats was developed. This approach is based on the findings that N-nitroamino acids (e.g., nitrosoproline (NPRO), nitrosohydroxyproline(NHPRO) and nitrososarcosine (NSAR)) when administered orally to rats, are excreted unchanged almost quantitatively (88-96% of the dose) in the urine and feces. After sequential administration of a nitrosatable amino acid and sodium nitrite, the nitrosamino acid excreted in the urine and feces was analyzed. The amount of nitrosoproline excreted in the urine of rats was proportional to the dose of proline and to the square of the nitrite dose. Co-administration of ascorbic acid and alpha-tocopherol together with the precursors decreased the urinary nitrosoproline whereas thiocyanate increased the yield. After feeding an amino acid precursor and nitrite, the yield of nitrosamino acids, formed in vivo and excreted in the urine increased in the order: nitrosoproline < nitrososarcosine < nitrosohydroxyproline. The same order was seen when the nitrosation rates of the amino acids in vitro were compared. Evidently, N-nitrosation in vivo in rats occurs via a similar mechanism as observed in vitro. Monitoring of N-nitrosamino acids excreted in the urine and feces appears to provide a valuable index for endogenous N-nitrosation. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

没有关于人类的数据。有充分的证据表明对动物具有致癌性。总体评估：2B组：该物质可能对人类具有致癌性。

No data are available in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 2B: The agent is possibly carcinogenic to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

N-亚硝基肌氨酸：合理预期为人类致癌物。

N-Nitrososarcosine: reasonably anticipated to be a human carcinogen.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：N-亚硝基肌氨酸

IARC Carcinogenic Agent:N-Nitrososarcosine

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：2B组：可能对人类致癌

IARC Carcinogenic Classes:Group 2B: Possibly 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论：第17卷：（1978年）一些N-亚硝基化合物

IARC Monographs:Volume 17: (1978) Some N-Nitroso Compounds

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

当对大鼠进行口服给药时，N-亚硝基氨基酸（例如，亚硝基脯氨酸（NPRO）、亚硝基羟基脯氨酸（NHPRO）和亚硝基肌氨酸（NSAR））几乎以不变的形式（剂量的88-96%）在尿液和粪便中排出。

...N-nitrosamino acids (e.g., nitrosoproline (NPRO), nitrosohydroxyproline (NHPRO) and nitrososarcosine (NSAR)) when administered orally to rats, are excreted unchanged almost quantitatively (88-96% of the dose) in the urine and feces. ...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险品运输编号：
  UN 2811
• 储存条件：
  20°C

反应信息

• 作为反应物：
  描述：

  N-亚硝基肌氨酸 在 SC(NH₂)2 sodium azide 、 硫酸 作用下， 以 水 、 溶剂黄146 为溶剂， 生成 肌氨酸
  参考文献：
  名称：

  Denitrosation of nitrosamines—a quantitative study. Reactions of N-methyl-N-nitrosoaniline, N-nitrosoproline, dimethylnitrosamine and N-nitrososarcosine

  摘要：

  Rate measurements are reported for the denitrosation of N-methyl-N-nitrosoaniline (NMNA), N-nitrosoproline (NPr), dimethylnitrosamine (DMN), N-nitrososarcosine (NS) and N-nitrosopyrrol-idine (NPy), in acid solution in the presence of nucleophilic catalysts in the following solvent systems: water, ethanol, various aqueous acetic acid solutions (up to 80% acetic acid) and acetonitrile. The reactivity sequence generally is found to be NMNA > NPr = ca. NS >> DMN = ca. NPy. The most reactive solvent system is 80% acetic acid-water containing bromide ion (or thiourea) as a nucleophilic catalyst. The results, together with some earlier work in water, are discussed (a) in terms of the changing relative reactivities of the nucleophiles as the polarity of the solvent is changed, and (b) in terms of the electron-withdrawing properties of any substituents which can effect both the protonation equilibria and also the rate constant for nucleophilic attack of the protonated form of the nitrosamine.

  DOI：

  10.1039/p29910001099
• 作为产物：
  描述：

  N,N-二甲基甘氨酸 在 dinitrogen tetraoxide 作用下， 以 四氯化碳 为溶剂， 反应 15.0h， 以24%的产率得到N-亚硝基肌氨酸
  参考文献：
  名称：

  Boyer, Joseph H.; Kumar, Govindarajulu; Pillai, T. Perumal, Journal of the Chemical Society. Perkin transactions I, 1986, p. 1751 - 1754

  摘要：

  DOI：

文献信息

• Expanding available pyrazole substitution patterns by sydnone cycloaddition reactions
  作者：A.W. Brown、J.P.A. Harrity

  DOI：10.1016/j.tet.2017.04.049

  日期：2017.6

  We report the use of alkynylsilanes for the regiocontrolled synthesis of pyrazoles from functionalised sydnones. The strategies outlined herein allow a range of pyrazoles to be accessed with substitution patterns that are otherwise not directly obtained with high selectivity by alkyne cycloadditions. Moreover, this study serendipitously highlighted a simple and convenient procedure for the synthesis

  我们报告了炔基硅烷用于从功能化的sydnones的吡唑的区域控制合成。本文概述的策略允许使用取代模式来访问一定范围的吡唑，否则该取代模式不能通过炔烃环加成直接以高选择性获得。而且，该研究偶然地强调了通过TBAF和二氯甲烷的组合来合成芳基单氟甲基醚的简单和方便的方法。
• Bioorthogonal Click and Release Reaction of Iminosydnones with Cycloalkynes
  作者：Sabrina Bernard、Davide Audisio、Margaux Riomet、Sarah Bregant、Antoine Sallustrau、Lucie Plougastel、Elodie Decuypere、Sandra Gabillet、Ramar Arun Kumar、Jijy Elyian、Minh Nguyet Trinh、Oleksandr Koniev、Alain Wagner、Sergii Kolodych、Frédéric Taran

  DOI：10.1002/anie.201708790

  日期：2017.12.4

  We report the discovery of a new bioorthogonal click‐and‐release reaction involving iminosydnones and strained alkynes. This transformation leads to two products resulting from the ligation and fragmentation of iminosydnones under physiological conditions. Optimized iminosydnones were successfully used to design innovative cleavable linkers for protein modification, thus opening up new areas in the

  我们报告发现了一种新的生物正交的点击释放反应，涉及到亚氨基sydnones和应变炔烃。这种转化导致在生理条件下亚氨基sydnones的连接和断裂产生两种产物。优化的亚氨基缩醛成功用于设计用于蛋白质修饰的创新性可裂解连接子，从而在药物释放和目标捕捞应用领域开辟了新领域。这种点击释放技术可在温和生物正交条件下为功能化的环辛炔交换蛋白质上的标签。
• 4-Halogeno-sydnones for fast strain promoted cycloaddition with bicyclo-[6.1.0]-nonyne
  作者：Lucie Plougastel、Oleksandr Koniev、Simon Specklin、Elodie Decuypere、Christophe Créminon、David-Alexandre Buisson、Alain Wagner、Sergii Kolodych、Frédéric Taran

  DOI：10.1039/c4cc03816a

  日期：——

  4-Halogeno-sydnones were found to be efficient dipole partners for the strain promoted click reaction with bicyclo-[6.1.0]-nonyne. This bioorthogonal reaction has been applied to protein labeling.

  4-卤代-悉尼酮被发现是双环[6.1.0]-壬炔进行应变促进点击反应的高效偶极伙伴。这种生物正交反应已被应用于蛋白质标记。

• Versatile New Reagent for Nitrosation under Mild Conditions
  作者：Jordan D. Galloway、Cristian Sarabia、James C. Fettinger、Hrant P. Hratchian、Ryan D. Baxter

  DOI：10.1021/acs.orglett.1c00637

  日期：2021.5.7

  Here we report a new chemical reagent for transnitrosation under mild experimental conditions. This new reagent is stable to air and moisture across a broad range of temperatures and is effective for transnitrosation in multiple solvents. Compared with traditional nitrosation methods, our reagent shows high functional group tolerance for substrates that are susceptible to oxidation or reversible transnitrosation

  在这里，我们报告了一种在温和的实验条件下进行反硝化的新化学试剂。这种新试剂在很宽的温度范围内对空气和湿气都稳定，并且对多种溶剂中的亚硝基化有效。与传统的亚硝化方法相比，我们的试剂对易氧化或可逆转亚硝化的底物显示出较高的官能团耐受性。首次在此访问了几种具有挑战性的亚硝基化合物，其中包括15种N个同位素。X射线数据证实了该试剂的两种旋转异构体在室温下是构型稳定的，尽管仅一种异构体对亚硝基化有效。计算分析描述了旋转异构体相互转化的能量，包括有趣的几何依赖性杂交效应。
• Synthesis and reactions of 9,10-diazatetracyclo-[6.3.0.0.^4,110.^5,9]undecanes
  作者：Gordon W. Gribble、Bradford H. Hirth

  DOI：10.1002/jhet.5570330333

  日期：1996.5

  The tandem 1,3-dipolar cycloaddition between sydnones and 1,5-cyclooctadiene provides 9,10-diazatetracyclo[6.3.0.0.4,110.5,9]undecanes (the Weintraub reaction) in modest to good yields.

  sydnones和1,5-环辛二烯之间的串联1,3-偶极环加成反应可提供9,10-二氮杂四环[6.3.0.0。]。4,11 0. 5,9 ]十一烷（Weintraub反应）适度至良好收率。