An excellent correlation was found between the metabolism of nitrosopyrrolidine and nitrosohexamethylenimine (probably via oxidation at the alpha-C) in rat liver microsomes and mutagenic potency in 2 bacterial mutagenic systems.
The structures of the DNA adducts formed in the metabolism of cyclic (carcinogen) N-nitrosamines are not known. The reactions with deoxyguanosine, catalyzed by porcine liver esterase, of alpha-acetoxy-N-nitrosopyrrolidine and 4-(carbethoxynitrosamino) butanal which are stable precursors to the reactive intermediates, alpha- hydroxy-N-nitrosopyrrolidine and 3-formyl-1-propanediazohydroxide, formed in the alpha-hydroxylation of the cyclic nitrosamine, N-nitrosopyrrolidine were studied. The same 2 major deoxyguanosine adducts were produced in each reaction. They were isolated by high-performance liquid chromatography and characterized by their UV spectra, mass spectra and proton magnetic resonance spectra. On the basis of these spectral data, the structures of the 2 major adducts were assigned as 3-(2-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8R- hydroxy-6R-methylpyrimido (1,2-a)purine-10(3H)one and 3-(2-deoxy-beta-D-erythro- pentofuranosyl)-5,6,7,8-tetrahydro-8S-h-ydroxy-6S-methylpyrimido(1,2,-a)purine- 10(3H)one, in which a new saturated 6-membered ring is formed by reaction at the 1- and N2-positions of deoxyguanosine. The same 2 adducts were formed in the reaction of crotonaldehyde (2-butenal) with deoxyguanosine. Mild acid hydrolysis of each of the 2 diastereomeric deoxyguanosine adducts yielded a pair of enantiomeric tricyclic 1,N2-guanine derivatives which had spectral properties in accordance with the assigned structures. Treatment of these tricyclic 1,N-2-guanine derivatives with sodium hydroxide and sodium borohydrate yielded N2-(3-hydroxy-1- methylpropyl) guanine, confirming the structural assignments. Unlike saturated dialkylnitrosamines which are metabolized to intermediates that give mainly 7-alkylation of deoxyguanosine, the intermediates formed in the alpha-hydroxylation of a cyclic nitrosamine, N-nitrosopyrrolidine, modify deoxyguanosine by forming cyclic 1,N2-adducts.
It is interesting to note that apparently all N,N-dialkylnitrosamines containing a tert-butyl group are noncarcinogenic. The list includes N-nitroso-1-proline, found in cured meats, particularly bacon. Although noncarcinogenic itself, nitrosoproline gives rise to the carcinogenic N-nitrosopyrrolidine during cooking. Aromatic nitrosamines are capable of transnitrosation, ie, under suitable conditions, their nitroso group can be transferred to appropriate amine-type compounds. It is thus possible that noncarcinogenic transnitrosating agents could form new carcinogenic N-nitroso compounds in the stomach.
Less than 1% of ip dose of NPYR appeared as n-nitroso-3-hydroxy-pyrrolidine in urine of rats. Alkylated base, which was not identified ... was isolated from hydrolysates of liver DNA. (3)h-NPYR administration to rats reacted with DNA and RNA; however, no products were characterized.
来源:Hazardous Substances Data Bank (HSDB)
代谢
NPYR已知的人类代谢物包括2-吡咯烷醇和1-亚硝基。
NPYR has known human metabolites that include 2-Pyrrolidinol, 1-nitroso-.
There is sufficient evidence of a carcinogenic effect of N-nitrosopyrrolidine in one experimental animal species. Although no epidemiological data were available, N-nitrosopyrrolidine should be regarded as if it were carcinogenic to humans.
No data are available in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 2B: The agent is possibly carcinogenic to humans.
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: Tumors at more than one site have been observed in two rodent species administered nitrosopyrrolidine orally. HUMAN CARCINOGENICITY DATA: None.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
N-亚硝基吡咯烷：合理预期为人类致癌物。
N-Nitrosopyrrolidine: 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-亚硝基吡咯烷
IARC Carcinogenic Agent:N-Nitrosopyrrolidine
来源:International Agency for Research on Cancer (IARC)
After ip administration of 6 mg/kg bw (2,5-(14)c)- or (3,4-(14)c)-NPYR to rats, these compounds were converted to (14)CO2 to extent of 18-25% within 6 hr; 7% of radioactivity was excreted in urine and only 1-2% in feces. Oral dose of 4 mg/kg bw (2,5-(14)c)-NPYR was converted to (14)CO2 to extent of 77%, while only 14% of dose of 650 mg/kg bw appeared as (14)CO2 in 24 hr.
Whole-body autoradiography performed with hemisections of mice at -80 °C and dry tape-sections, using pretreated and non-pretreated mice, indicated uniform distribution of non-metabolized N-nitrosopyrrolidine in tissues. At the shortest survival intervals (1 and 5 min) a high level of metabolites were found in liver, tracheo-bronchial and nasal mucosa and harder's gland which indicates local formation of metabolites in these tissues. At later survival intervals (0.5-24 hr) metabolites were in addition found in tissues with rapid cell turnover and high rate of protein synthesis and in brown fat.
... Nitrosamines ... can presumably cross the placenta since they are capable of inducing neoplasma in the offspring if administered to rats in late pregnancy. /Nitrosamines/
Differential pulsed polarography in 0.05M sulfuric acid was used for the determination of urinary concentration of nonmetabolized N-nitrosamines in rats 24-72 hr after intragastric administration of 0.01-0.5 LD50 of ... N-nitrosopyrrolidine. ... Most of the nitrosamines were recovered in urine in less than or equal to 10% of the administered amounts. ...
Selective N-Nitrosation of Amines,<i>N</i>-Alkylamides and<i>N</i>-Alkylureasby N<sub>2</sub>O<sub>4</sub>Supported on Cross-Linked Polyvinylpyrrolidone(PVP-N<sub>2</sub>O<sub>4</sub>)
N2O4 was supported on the cross-linked polyvinylpyrrolidone (PVP) to afford a solid, stable and recyclable nitrosating agent. This reagent shows excellent selectivity for N-nitrosation of dialkyl amines in the presence of diaryl-, arylalkyl-, trialkylamines and also for secondary amides in dichloromethane at room temperature under mild and heterogeneous conditions. Also N-nitroso-N-alkyl amides can be selectively prepared in the presence of primary amides and N-phenylamides under similar reaction conditions. Selective N-nitrosation or dealkylation and N-nitrosation of tertiary amines can also be performed by this reagent.
Reactions of trifluoroamine oxide: a route to acyclic and cyclic fluoroamines and N-nitrosoamines
作者：Om Dutt Gupta、Robert L. Kirchmeier、Jean'ne M. Shreeve
DOI：10.1021/ja00162a045
日期：1990.3
Preparation de fluoroamines et de nitrosoamines secondaires acycliques R 2 NF et R 2 NNO (R=CH 3 ,C 2 H 5 ,n-C 3 H 7 ,i-C 3 H 7 ,n-C 4 H 9 ,i-C 4 H 9 ,c-C 6 H 11 ) et de fluoroamines et nitrosoamines heterocycliques satures RNF et RNNO (R=c-C 4 H 8 ,c-C 5 H 10 ,(CH 3 ) 2 -2,6-c-C 5 H 8 ,(CH 3 ) 4 -2,2,6,6-c-C 5 H 6 ) par reaction des amines correspondantes avec NF 3 O
制备去氟胺和去亚硝基胺二类无环R 2 NF 和R 2 NNO (R=CH 3 ,C 2 H 5 ,nC 3 H 7 ,iC 3 H 7 ,nC 4 H 9 ,iC 4 H 9 ,cC 6 H 11 ) et de fluoroamines et nitrosoamines 杂环饱和 RNF et RNNO (R=cC 4 H 8 ,cC 5 H 10 ,(CH 3 ) 2 -2,6-cC 5 H 8 ,(CH 3 ) 4 -2,2,6 ,6-cC 5 H 6 ) par 反应脱胺对应物 avec NF 3 O
Formation of <i>N</i>-Nitrosamines and <i>N</i>-Nitramines by the Reaction of Secondary Amines with Peroxynitrite and Other Reactive Nitrogen Species: Comparison with Nitrotyrosine Formation
作者：Mitsuharu Masuda、Howard F. Mower、Brigitte Pignatelli、Irena Celan、Marlin D. Friesen、Hoyoku Nishino、Hiroshi Ohshima
DOI：10.1021/tx990120o
日期：2000.4.1
mechanism, involving one-electron oxidation by peroxynitrite of secondaryamines to form amino radicals (R(2)N(*)), which react with nitric oxide ((*)NO) or nitrogen dioxide ((*)NO(2)) to yield nitroso and nitro secondaryamines, respectively. Reaction of morpholine with NO(*) and superoxide anion (O(2)(*)(-)), which were concomitantly produced from spermine NONOate and by the xanthine oxidase systems, respectively
Visible-Light-Induced Photoaddition of <i>N</i>-Nitrosoalkylamines to Alkenes: One-Pot Tandem Approach to 1,2-Diamination of Alkenes from Secondary Amines
作者：Dilip V. Patil、Tengda Si、Hun Young Kim、Kyungsoo Oh
DOI：10.1021/acs.orglett.1c00786
日期：2021.4.16
excitation at 453 nm. The developed visible-light-promoted photoadditionreaction of N-nitrosoamines to alkenes was combined with the o-NQ-catalyzed aerobic oxidation protocol of amines to telescope the direct handling of harmful N-nitroso compounds, where the desired α-amino oxime derivatives were obtained in a one-pot tandem N-nitrosation and photoaddition sequence.
Facile N-Nitrosation of Secondary Amines Using Poly(N,N&#39;-dibromo-Nethylene- benzene-1,3-disulfonamide)and N,N,N&#39;,N&#39;-tetrabromobenzene- 1,3-disulfonamide/NaNO<sub>2</sub> Under Mild Conditions
In this research project, a combination of poly(N,N'-dibromo-N-ethylene-benzene-1,3-disulfonamide) [PBBS]
and/or(N,N,N',N'-tetrabromobenzene-1,3-disulfonamide) [TBBDA] with sodium nitrite in the presence of wet SiO2 (50%
w/w) was used as an efficient nitrosating agent for the conversion of secondary amines to their corresponding nitroso
compounds. N-Nitrosation reaction has been performed in dichloromethane at room temperature under mild and heterogeneous
conditions. The reaction is operationally simple and corresponding products were achieved in good to excellent
yields.
