- The nitrosation of N-alkylureas: Evidence for a proton transfer mechanism
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The kinetics of the nitrosation of methyl, ethyl, propyl, butyl, and allyl urea were studied by conventional and stopped-flow spectrophotometry in the presence or absence of acetate or mono-, di-, or trichloroacetate anions In the presence of a large excess of urea, the observed rate equation was chemical equations presented where Ka is the acidity constant of nitrous acid and KR that of the carboxylic acid The ureas exhibited the reactivity order methylurea ? (ethylurea ≈ propylurea ≈ butylureal ? allylurea. Experiments in D2O afforded values of kH2O/kD2O in general agreement with the values 4.1-5 5 predicted by a semiclassical transition state theory of kinetic isotope effects [i.e., kH2O/kD2O = exp(0.130hv/kT)]where v is the frequency of R3N - H stretching (2700-2250 cm-1) in the protonated urea. This result, the observed catalysis by carboxylate ions and the value of the Bronsted parameter β(0.45) show the rate-controlling step of these reactions to be the transfer of a proton from the protonated N-alkyl-N-nitrosourea to the solvent or to the organic anion. if present. The observed order of substrate reactivities is explicable in terms of the capacity of the protonated N-alkyl-N-nitrosourea for forming a hydrogen bond with the water molecule to which the proton will be transferred, and the degree to which the formation of such bonds is hindered by the hydrophobic alkyl chain of the nitrosourea.
- Casado, Iulio,Gonzalez-Alatorre, Guillermo,Izquierdo, Carmen,Brunner, Christian
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- Polyprenylated benzophenone derivatives with a novel tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton from Clusia burle-marxii exhibited cytotoxicity against GL-15 glioblastoma-derived human cell line
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Three new polyprenylated benzophenone derivatives (1–3) were identified in the hexane extract of Clusia burle-marxii trunks, through the isolation and structural elucidation of their methyl derivatives, along with two known polyprenylated benzophenone derivatives sampsonine N (4) and obdeltifolione C (5). Burlemarxiones A (1) and B (2) show an unprecedent tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton. These compounds are a pair of β-diketones in tautomeric equilibrium, whereas isonemorosonol (3) is the respective β-diketone pair in tautomeric equilibrium with nemorosonol. Burlemarxione A methyl derivative (1a) and sampsonine N exhibited strong in vitro cytotoxic activity against GL-15 glioblastoma-derived human cell line.
- Ferraz, Caline G.,Ribeiro, Paulo R.,Marques, édson J.,Mendon?a, Renata,Guedes, Maria Lenise S.,Silveira, Edilberto R.,El-Bachá, Ramon,Cruz, Frederico G.
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- REACTION MECHANISM OF THE NISTOSATION OF UREAS.
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The nitrosation of methylurea has been studied under catalysis by acetate and mono-, di- and trichloroacetate buffers. The catalysis observed has been found to be due to the organic anions, and Bronsted relation is obeyed with beta equals 0. 24. The experimental results have been interpreted in terms of a reaction mechanism which features the rapid formation of an intermediate, MeNH(NO)CONH//2, when the methylurea is nitrosated. The rate controlling step is the transfer of a proton from this intermediate to the solvent or to a basic catalyst (the nitrite ion or the organic anion). That it is this step that controls the overall rate of reaction is supported by the isotopic effect (k//H/k//D equals 3. 5) observed on carrying out kinetic measurements in D//2O.
- Casado,Castro,Mosquera,Rodriguez Preito,Vazquez Tato
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- Novel polyprenylated benzophenone derivatives from Clusia burle-marxii
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Three new caged polyprenylated benzophenone derivatives named burlemarxiones D-F (1–3) were isolated from the hexane extract of Clusia burle-marxii trunks. Burlemarxione D (1) contains the tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton also observed for burlemarxione A, its probable immediate precursor. However, two additional rings are formed to produce an unprecedented complex-caged core skeleton. These additional rings could be formed by a radical cyclization reaction of one prenyl group at C-5 with C-1 and C-33, followed by oxidative dehydrogenation (rearomatization) or by an intramolecular [4 + 2] radical cycloaddition (Diels-Alder reaction), followed by an enolization reaction (rearomatization). Burlemarxiones E and F were isolated after methylation with diazomethane that was necessary to avoid the interconversion of the pair of β-diketones in tautomeric equilibrium. The proposed biosynthetic pathway for burlemarxiones D-F involves the condensation of either lavandulyl pyrophosphate or 2-(1-methylvinyl)-hexa-5-enyl pyrophosphate with the acylphloroglucinol derivative 6-benzoyl-5-hydroxy-5-cyclohexen-1,3-dione, followed by consecutive prenylation reactions. Therefore, Clusia burle-marxii reinforces the claim that the genus Clusia is an important source of sophisticated caged polyprenylated benzophenone derivatives.
- Ferraz, Caline G.,Ribeiro, Paulo R.,Mendon?a, Renata,Silveira, Edilberto R.,Cruz, Frederico G.
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- Kinetic study of the nitrosation of N-alkylureas in dioxane-acetic acid mixtures
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The rate constants were determined for the nitrosation reactions of the following substrates: Methyl (MU), Ethyl (EU), Propyl (PU)Butyl (BU), and Allylurea (AU). The rate equation found at a constant pH was: v = k[HNO2] [Urea]. The reactions were carried out in predominantly organic media(dioxane-acetic acid-water) with differing polarities. The proposed reaction mechanism involves the proton transfer from the protonated N-alkyl-N-nitrosourea to the acetate anion. As the polarity of the medium decreased, an approximation of the rate constants of the nitrosation of the different substrates was observed. This approximation can be interpreted as a function of the impediment generated by the R alkyl radical in the rate controlling step. Accordingly, the substrate reactivity will be associated with the ease in which the protonated N-alkyl-N nitrosurea can transfer the proton to the acetate anion. The results achieved in this study are in accordance with there activities observed in the nitrosation of these substrates in aqueous media MU ? (EU ≈ PU ≈ BU) > AU.
- Alatorre,Zapiain,Quintana,Martinez
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- Transnitrosation of non-mutagenic N-nitrosoproline forms mutagenic N-nitroso-N-methylurea
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Abstract N-Nitroso-N-methylurea (NMU) is a potent carcinogen and suspected as a cause of human cancer. In this study, mutagenic NMU was detected by HPLC after the transnitrosation of non-mutagenic N-nitrosoproline (NP) to N-methylurea in the presence of thiourea (TU) under acidic conditions. The structure of NMU was confirmed by comparing 1H NMR and IR spectra with that of authentic NMU after fractionation by column chromatography. Furthermore, a fraction containing NMU formed by transnitrosation was mutagenic in Salmonella typhimurium TA1535. NMU was formed in the reaction of NP and N-methylurea in the presence of 1,1,3,3-tetramethylthiourea (TTU) or 1,3-dimethylthiourea in place of TU as an accelerator. The reaction rate constants (k) for NMU formation were correlated with their nucleophilicity of sulfur atom in thioureas. The N-methylurea concentration did not affect the NMU formation, whereas the rate of NMU formation correlated linearly with concentrations of NP, TTU and oxonium ion. The observed kinetics suggests a mechanism by which the nitroso group was transferred directly from the protonated NP to the thiourea then to N-methylurea to form NMU. The rate-determining step was the formation of the complex with the protonated NP and thiourea.
- Inami, Keiko,Shiino, Junko,Hagiwara, Shin,Takeda, Kei,Mochizuki, Masataka
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- Regioselective Synthesis of [6,6]-Open and [5,6]-Closed C70(CF3)8[CH2] Methanofullerenes with Rapid [6,6]-to-[5,6] Phototransformation
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Fullerene derivatives with >CH2 addends in [6,6]-open or [5,6]-closed configuration are uncommon of fullerene derivatives, but they are readily accessible via treatment of Cs-C70(CF3)8 with diazomethane followed by thermolysis or photolysis. Both thermodynamic and kinetic factors favor regioselective addition of diazomethane at the near-equatorial [5,6]-double bond of Cs-C70(CF3)8 to give a thermally labile pyrazoline intermediate. Thermal extrusion of N2 from the latter is a kinetically controlled process with orbital symmetry controlled Woodward–Hoffmann-allowed mechanism. It quantitatively yields the less thermodynamically favorable [6,6]-open isomer of C70(CF3)8[CH2] homofullerene, but the latter turns out to be capable of unexpectedly rapid quantitative phototransformation into the thermodynamically preferable [5,6]-closed methanofullerene isomer. The transformation involves the manifold of the triplet states that facilitate the required cleavage of the Ccage–CH2 bonds.
- Semivrazhskaya, Olesya O.,Belov, Nikita M.,Rybalchenko, Alexey V.,Markov, Vitaliy Yu.,Ioffe, Ilya N.,Lukonina, Natalia S.,Troyanov, Sergey I.,Kemnitz, Erhard,Goryunkov, Alexey A.
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- Method for synthesizing chiral 4-(N-carbobenzoxy) pyrrolidone
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The invention provides a method for synthesizing chiral 4-(N-carbobenzoxy) pyrrolidone. L-asparaginate is adopted as an initial raw material, through four steps of reactions of amino protection, diazo-reactions, carbonyl reduction and cyclization, chiral 4-(N-carbobenzoxy) pyrrolidone is prepared, raw materials are low in price and easy to obtain, chiral resolution is not needed in the reaction process, the yield is high, the reaction speed is rapid, a small amount of byproducts are generated, and the method is very applicable to industrial application.
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Paragraph 0025; 0030
(2019/10/01)
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- Noncanonical RNA Nucleosides as Molecular Fossils of an Early Earth—Generation by Prebiotic Methylations and Carbamoylations
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The RNA-world hypothesis assumes that life on Earth started with small RNA molecules that catalyzed their own formation. Vital to this hypothesis is the need for prebiotic routes towards RNA. Contemporary RNA, however, is not only constructed from the four canonical nucleobases (A, C, G, and U), it also contains many chemically modified (noncanonical) bases. A still open question is whether these noncanonical bases were formed in parallel to the canonical bases (chemical origin) or later, when life demanded higher functional diversity (biological origin). Here we show that isocyanates in combination with sodium nitrite establish methylating and carbamoylating reactivity compatible with early Earth conditions. These reactions lead to the formation of methylated and amino acid modified nucleosides that are still extant. Our data provide a plausible scenario for the chemical origin of certain noncanonical bases, which suggests that they are fossils of an early Earth.
- Schneider, Christina,Becker, Sidney,Okamura, Hidenori,Crisp, Antony,Amatov, Tynchtyk,Stadlmeier, Michael,Carell, Thomas
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supporting information
p. 5943 - 5946
(2018/04/30)
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- A scalable and safe continuous flow procedure for in-line generation of diazomethane and its precursor MNU
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Diazomethane is a valuable C1-building block for organic synthesis. Due to its intrinsic reactivity and instability, handling of this reagent is associated with serious safety hazards. Herein we present a simple and robust continuous flow process, allowing a safe and on-demand generation of diazomethane with a productivity of 95-117 mmol h-1. The developed two-step process starts from non-hazardous N-methylurea, and generates and consumes N-methyl-N-nitrosourea (MNU) and diazomethane, thus enabling a safe and convenient scale-up to a multi-gram scale in a conventional synthesis laboratory.
- Lehmann
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supporting information
p. 1449 - 1453
(2017/05/10)
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- A SOLID FORM OF (-)-AMBROX FORMED BY A BIOVERVERSION OF HOMOFARNESOL IN THE PRESENCE OF A BIOCATALYST
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A solid form of (-)-Ambrox formed by a bioconversion process.
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Page/Page column 33
(2017/11/15)
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- Metal-Free Ring-Expansion Reaction of Six-membered Sulfonylimines with Diazomethanes: An Approach toward Seven-Membered Enesulfonamides
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A new metal-free, ring-expansion reaction of six-membered N-sulfonylimines with unstable diazomethanes, generated in situ from the N-tosylhydrazones, has been developed. This reaction delivers valuable seven-membered enesulfonamides by a Tiffeneau-Demjanov rearrangement and intramolecular proton transfer tautomerization process. Moreover, this ring-expansion reaction can be carried out in a one-pot fashion and scaled up to the gram scale by using aryl aldehydes, without the need to isolate the N-tosylhydrazone. A diazo thing: The title reaction between cyclic N-sulfonylimines and diazo compounds generated in situ from the N-tosylhydrazones is simple and functional-group tolerant. It thus delivers valuable seven-membered sulfonamides in up to 95 % yield. Moreover, this reaction can be carried out in one-pot starting from the aryl aldehydes, without the need to isolate the N-tosylhydrazone (right).
- Xia, An-Jie,Kang, Tai-Ran,He, Long,Chen, Lian-Mei,Li, Wen-Ting,Yang, Jin-Liang,Liu, Quan-Zhong
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supporting information
p. 1441 - 1444
(2016/02/12)
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- Access to P-Stereogenic Phosphinates via N-Heterocyclic Carbene-Catalyzed Desymmetrization of Bisphenols
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A carbene-catalyzed desymmetrization of prochiral bisphenol compounds bearing remote P-stereogenic centers is disclosed. The catalytic reactions can be performed on gram scales with 1 mol % N-heterocyclic carbene (NHC) catalyst, providing efficient access to enantiomerically enriched P-stereogenic phosphinates. The chiral phosphinates prepared with our method can find widespread applications as asymmetric organic catalysts and ligands.
- Huang, Zhijian,Huang, Xuan,Li, Baosheng,Mou, Chengli,Yang, Song,Song, Bao-An,Chi, Yonggui Robin
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supporting information
p. 7524 - 7527
(2016/07/06)
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- IMPROVEMENTS IN OR RELATING TO ORGANIC COMPOUNDS
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A process of converting a carbon-carbon multiple bond to a cyclopropane ring, comprising the addition of a N-alkyl-N-nitroso compound to a mixture of alkene precursor, aqueous base and Pd(II)-catalyst, with the N-alkyl-N-nitroso compound obtained directly from an alkyl amine derivative, NaNO2 and an acid via phase separation of the N-alkyl-N-nitroso compound from the aqueous phase.
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Page/Page column 17
(2015/05/06)
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- KDM1A INHIBITORS FOR THE TREATMENT OF DISEASE
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Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDMIA, and methods of increasing gamma globin gene expression in a human or animal subject are also provided for the treatment diseases such as sickle cell disease.
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Paragraph 0265-0267
(2014/10/18)
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- Cyclobutane derivatives as novel nonpeptidic small molecule agonists of glucagon-like peptide-1 receptor
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A novel cyclobutane class of nonpeptidic glucagon-like peptide-1 (GLP-1) receptor agonists, exemplified by 3, was identified using receptor binding and multiple response element/cAMP response element (MRE/CRE)-driven reporter gene assays. The structures of 3 and its three isomers were elucidated by NMR, HRESIMS, and X-ray crystallography. A series of structural modifications were also made based on the core structure of 3 with different substitution groups at the west and east ends. Among these analogues, compound 16 was found to be 4- to 5-fold more potent than 3 both in vitro and in vivo.
- Liu, Qing,Li, Na,Yuan, Yunyun,Lu, Huili,Wu, Xiaoyan,Zhou, Caihong,He, Min,Su, Haoran,Zhang, Meng,Wang, Jia,Wang, Bao,Wang, You,Ma, Dawei,Ye, Yang,Weiss, Hans-Christoph,Gesing, Ernst R. F.,Liao, Jiayu,Wang, Ming-Wei
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supporting information; experimental part
p. 250 - 267
(2012/03/10)
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- Hydrogen peroxide and arenediazonium salts as reagents for a radical beckmann-type rearrangement
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The reductive ring-opening of hydroperoxides derived from cyclic ketones leads to alkyl radicals which can effectively be trapped by arenediazonium salts. This synthetic transformation yielding azo carboxylic acids or lactams, after a reductive step, can be classified as a radical version of the well-known Beckmann rearrangement. In this article, we present results on the scope, the limitations and possible applications of this new reaction type. Georg Thieme Verlag Stuttgart · New York.
- Prechter, Agnes,Heinrich, Markus R.
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experimental part
p. 1515 - 1525
(2011/06/24)
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- Application of N-nitrosoureas in the synthesis of organophosphorus compounds
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N-nitrosoureas which are readily accessible from the reaction of urea derivatives with sodium nitrite and aqueous H2SO4 reacted with acetylenic esters in the presence of Ph3P in ethyl acetate at ambient pressure to give stable phosphorus ylides. This methodology is introduced as a simple and inexpensive procedure for the preparation of organophosphorus compounds in excellent yields.
- Afshar, Davood Aghaei,Islami, Mohammad Reza
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scheme or table
p. 509 - 511
(2009/04/06)
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- Syntheses of novel 1,3-diazaazulene derivatives and their nonlinear optical characterization
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We have synthesized three new 1,3-diazaazulene derivatives, namely, 2-(4′-N,N-dimethylaminophenyl)-6-nitro-1,3-diazaazulene (18, DMAPNA), 2-(4′-aminophenyl)-6-nitro-1,3-diazaazulene (19, APNA) and 2-[4′-N-(2-hydroxyethyl)aminophenyl]-6-nitro-1,3-diazaazulene (20, HEAPNA), each of them contains an amino substitute as the electron donor (D), 2-phenyl-1,3-diazaazulene as the π-conjugated bridge and a nitro as the electron acceptor (A). Our theoretical results have predicted that these D-π-A type chromophores possess low ground-state dipole moment (μg) and large first-order hyperpolarizability (β), which may facilitate a low degree of aggregation for the chromophores dispersed in a polymeric matrix as well as a large nonlinear optical (NLO) response. The expected NLO performance has been confirmed by the experimental β and μg values, e.g., for 18, 407.8 × 10-30 esu and 4.7 D, respectively. The origins of large β and low μg are explained in terms of a two-state quantum model. The DMAPNA (18)-doped and poled polymethylmethacrylate film exhibits a large second harmonic generation (SHG) coefficient of d33 = 10.9 pm V-1 with excellent thermal stability (above 70% of the maximal SHG coefficient remains at ~100 °C). The Royal Society of Chemistry.
- Zhu, Yun-Ji,Qin, An-Jun,Fu, Li-Min,Ai, Xi-Cheng,Guo, Zhi-Xin,Zhang, Jian-Ping,Ye, Cheng
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p. 2101 - 2106
(2008/02/07)
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- Dinitrogen tetroxide-impregnated charcoal (N2O 4/charcoal): Selective nitrosation of amines, amides, ureas, and thiols
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Efficient N-nitrosation of amines, amides, and ureas, and also S-nitrosation of thiols were performed with dinitrogen tetroxide impregnated on activated charcoal (N2O4/charcoal) in CH 2Cl2 at room temperature. High selectivity was observed for N-nitrosation of dialkyl amines, N-alkylamides and N-alkylureas. Dealkylation and N-nitrosation of trialkylamines were also performed by this reagent. Copyright Taylor & Francis, Inc.
- Iranpoor, Nasser,Firouzabadi, Habib,Pourali, Ali Reza
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p. 1517 - 1526
(2007/10/03)
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- Selective N-nitrosation of amines, N-alkylamides and N-alkylureas by N2O4 supported on cross-linked polyvinylpyrrolidone (PVP-N2O4)
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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.
- Iranpoor, Nasser,Firouzabadi, Habib,Pourali, Ali-Reza
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p. 1591 - 1597
(2007/10/03)
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- Tart cherry compounds that have antioxidant activity and uses thereof
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Compounds that are isolatable from cherries and have antioxidant activity, and methods for isolating these compounds are described. In particular, the invention relates to 1-(3',4'-dihydroxycinnamoyl)-cyclopenta-2,3-diol and 1-(3',4'-dihydroxycinnamoyl)-cyclopenta-2,5-diol, which have antioxidant activity. These antioxidant compounds and compositions containing these compounds are useful as food preservatives, dietary supplements, nutraceuticals, and phytoceuticals.
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- The mechanism of decomposition of N-methyl-N-nitrosourea (MNU) in water and a study of its reactions with 2'-deoxyguanosine, 2'-deoxyguanosine 5'-monophosphate and d(GTGCAC)
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The carcinogenicity of N-methyl-N-nitrosourea (MNU) arises, from its ability to methylate DNA, This occurs in an aqueous environment and therefore an appreciation of the mode of decomposition of MNU in water is essential to understanding the mechanism of DNA methylation and its base sequence dependence. The kinetics of MNU hydrolyses are shown to be first order in MNU with a steep rise in rate above pH 8. Using NMR for in situ monitoring of reaction intermediates and products from hydrolyses of [13CO]MNU, [15NH2]MNU and [13CH3]MNU, it is proved that base-induced hydrolysis of MNU is initiated by deprotonation at the carbamoyl group. The critical reactive species are shown to be the methyldiazonium ion (Me-N2+) and cyanate (NCO-). Investigations of reactions of [13CH3]MNU with 2'-deoxyguanosine (dGuo) and 2-deoxyguanosine 5'-monophosphate (dGuo-5P) showed that: a) the site of methylation of dGuo is highly pH-dependent (relatively more N-1 and O6-methylation compared to N-7 occurs at higher pH; b) the principal site of methylation of dGuo-5P by MNU is at phosphate; c) incorporation of deuterium into methyl groups occurs in D2O at higher pH. Methylation of the oligonucleotide d(GT[15N]GCAC) by MNU in D2O showed partial deuteriation of the N7-methyl groups of the guanines, whilst methylation by MNU in water indicated no significant preference for either guanine with respect to N7-methylation.
- Golding, Bernard T.,Bleasdale, Christine,McGinnis, Joseph,Mueller, Susanna,Rees, Hue Thu,Rees, Nicholas H.,Farmer, Peter B.,Watson, William P.
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p. 4063 - 4082
(2007/10/03)
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- A screening procedure for the formation of nitroso derivatives and mutagens by drug-nitrite interaction
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A general procedure for screening for the formation of nitroso derivatives and/or mutagens by drug-nitrite interaction was established. A test drug (50 mM) was reacted with nitrite (500 mM) at pH 3.0-3.5 and 37°C for 4 h. The residual nitrite in the reaction mixture was decomposed with ammonium sulfamate. The nitrite-free reaction mixture was assayed for both nitroso derivatives and mutagens by colorimetry of Griess reagent-positive substances formed by treatment with hydrogen bromide and by mutagenesis assay using Salmonella typhimurium TA98 and TA100 as tester strains, respectively.
- Takeda,Kanaya
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p. 3399 - 3404
(2007/10/02)
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- Conformational Preferences in Alkylnitrosoureas
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The spectroscopic properties of several N-alkyl-N-nitrosoureas, N,N'-dialkyl-N-nitrosoureas, and N,N',N'-trialkyl-N-nitrosoureas have been studied in carbon disulfide and chloroform solutions.The NH stretching frequencies in the IR spectra have been observed in both concentrated and dilute solution and in the presence of added dioxane.The results indicate that there is a strong intramolecular hydrogen bond in the mono- and dialkylnitrosoureas.The chemical shifts and line widths of the NMR spectra have also been studied in these solvents.The large chemical shift differences, about 1.3 ppm, for the NH protons in the monoalkylnitrosoureas and other spectroscopic features in the monoalkyl- and dialkylnitrosoureas also indicate that an intramolecular hydrogen bond contributes to a strong conformational preference.The temperature dependence of the NMR spectra of several N,N',N'-trialkyl-N-nitrosoureas establishes that the energy barrier for rotation about the carbon dialkylamide bond is about 13 kcal mol-1.Dipolar resonance interactions are primarily responsible for this barrier.This interaction is augmented by a strong, 8-10 kcal mol-1, hydrogen bond in the mono- and dialkylnitrosoureas.
- Snyder, John K.,Stock, Leon M.
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p. 886 - 891
(2007/10/02)
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- The Absence of Nucleophilic Catalysis in the Nitrosation of Amides. Kinetics and Mechanism of the Nitrosation of Methylurea and the Reverse Reaction
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Rate constants have been determined for the nitrosation of methylurea (MU) in acid solution and also for the reverse reaction, the denitrosation of N-methyl-N-nitrosourea (MNU).The nitrosation reaction is essentially irreversible at the low acidities (0.01-0.4M-H2SO4) chosen for the experiments whereas the denitrosation reaction was examined at higher acidities (0.5-2.7M-H2SO4) in the presence of excess of hydrazine sulphate (a trap for free nitrous acid) when it is irreversible.For nitrosation the rate law, rate = k+> was established and there was no catalysis by substantial concentrations of added potassium bromide or potassium thiocyanate.Similarly the rate law for denitrosation was found to be rate = khA (where hA is the acidity function used for the protonation of amides), and again there was no catalysis by added potassium bromide, potassium thiocyanate,or thiourea.Te absence of nucleophilic catalysis in the nitrosation of amides had previously been noted and is a puzzling feature when comparison is made with the well established catalysis for amines.This is explained, together with the other observed results, by a detailed consideration of the individual kinetic steps involved in both reactions, and in particular by application of a limiting condition to both forward and reverse reactions in which the actual rate constant for the denitrosation process in an amide is very large compared with the proton transfer to the solvent from the intermediate.
- Hallett, Geoffrey,Williams, D. Lyn H.
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p. 1372 - 1375
(2007/10/02)
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- Nitrosourea derivatives of glycosides
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New nitrosourea derivatives are provided, which possess a high inhibitory activity against the leukemia and tumors with a low toxicity and which are useful for pharmaceutical purposes. The compounds have the formula STR1 WHEREIN A represents a glycosyl group, a monovalent residue of methyl glucoside or of alditol, a N-substituted carbamoyloxyalkyl group or a hydroxy-substituted cyclohexyl group when n is 1, or A represents a tetravalent residue of ribostamycin when n is 4 and R represents a lower alkyl or halo-alkyl group and are prepared by treating a compound of the formula STR2 WITH A NITROSATING AGENT.
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