Synthesis of nitrolipids. All four possible diastereomers of nitrooleic acids: (E)- and (Z)-, 9- and 10-nitro-octadec-9-enoic acids

Unsaturated fatty acids are nitrated endogenously to produce nitrated lipids. Recent studies have shown that these nitrated lipids have high chemical reactivity and profound biological implications. We report an efficient, scalable synthesis which is regiospecific and stereoselective for all possible isomers of nitrated oleic acid: (E)- and (Z)-, 9- and 10-octadec-9-enoic acids.     

Synthesis and nitration of 7-alkylquinolines

The Skraup synthesis with m-ethylaniline has been shown to give a mixture of 7-ethylquinoline (75%) and 5-ethylquinoline (25%). Pure 7-ethylquinoline has been isolated as a solid. Nitration of 7-methyl- and 7-ethylquinolines gives only the 8-nitro derivatives; the minor products from the nitration of impure samples of 7-alkylquinolines arise from the 5-alkyl- contaminants. 5-Methylquinoline is nitrated at the 6- and 8-positions.     

Picrylamino-substituted heterocycles. IV. Pyrazoles

This paper describes the synthesis of various picryl- and picrylamino-substituted pyrazoles. These compounds were prepared by condensing the appropriate pyrazole or aminopyrazole with a picryl halide or picrylpyrazole. Some of these materials could be nitrated under carefully controlled conditions to the corresponding nitropyrazole derivatives. The products were identified by n.m.r. spectroscopy, and their crystal densities and thermal stabilities were determined. Drop-weight impact sensitivities were measured for some of the more interesting compounds.     

Nitration of aromatic compounds under neutral conditions using the Ph2PCl/I2/AgNO3 reagent system

Aromatic compounds were nitrated efficiently under essentially neutral conditions by employing Ph₂PCl in the presence of I₂ and AgNO₃. This method minimizes waste products compared to traditional methods and gives the corresponding mononitro derivatives in good to excellent yields in dichloromethane at room temperature.     

Nitration of 2-(2-quinolyl)thiophene and 5-(2-quinolyl)-2,2′-dithiophene

2-(2-Quinolyl)thiophene is nitrated in the 5 position, while its 2-thiophenyl analog is nitrated in the 3′ and 5′ positions simultaneously.     

Reactions of hydro(pero)xy derivatives of polyunsaturated fatty acids/esters with nitrite ions under acidic conditions. Unusual nitrosative breakdown of methyl 13-hydro(pero)xyoctadeca-9,11-dienoate to a novel 4-nitro-2-oximinoalk-3-enal product

13(S)-hydroperoxy- and 13(S)-hydroxyoctadeca-9,11-dienoic acids (1a/b), 15(S)-hydroperoxy- and 15(S)-hydroxyeicosa-5,8,11,13-tetraenoic acids (2a/b), and their methyl esters reacted smoothly with NO2- in phosphate buffer at pH 3-5.5 and at 37 degrees C to afford mixtures of products. 1b methyl ester gave mainly the 9-nitro derivative 3b methyl ester (11% yield) and a peculiar breakdown product identified as the novel 4-nitro-2-oximinoalk-3-enal derivative 4 methyl ester (15% yield). By GC-MS hexanal was also detected among the products. Structures 3b and 4 methyl esters were secured by 15N NMR analysis of the products prepared from 1b methyl ester upon reaction with Na15NO2. 4 methyl ester (14% yield) was also obtained from 1a methyl ester along with the nitrated hydroperoxy derivative 3a methyl ester (10% yield). Under the same conditions, 2a/b methyl esters gave mainly the corresponding nitrated derivatives 5a/b, with no detectable breakdown products, whereas the model compound (E,E)-2,4-hexadienol (6) afforded two main nitrated derivatives identified as 7 and 8. A reaction pathway for 1a/b methyl esters was proposed involving conversion of nitronitrosooxyhydro(pero)xy intermediates which would partition between two competing routes, viz., loss of HNO2, to give 3a/b methyl esters, and a remarkably facile fission leading to 4 methyl ester and hexanal.     

Gas-solid reactions of single crystals: a study of reactions of NH3 and NO2 with single crystalline organic substrates by infrared microspectroscopy

Reaction of single crystals of benzoic and trans-cinnamic acids with 200 Torr pressure of ammonia gas in a sealed glass bulb at 20 degrees C generates the corresponding ammonium salts; there is no sign of any 1:2 adduct as has been reported previously for related systems. Isotopic substitution using ND3 has been used to aid identification of the products. Adipic acid likewise reacts with NH3 gas to form a product in which ammonium salts are formed at both carboxylic acid groups. Reaction of 0.5 Torr pressure of NO2 gas with single crystals of 9-methylanthracene and 9-anthracenemethanol in a flow system generates nitrated products where the nitro group appears to be attached at the 10-position, i.e. the position trans to the methyl or methoxy substituent on the central ring. Isotopic substitution using 15NO2 has been used to confirm the identity of the bands arising from the coordinated NO2 group. The products formed when single crystals of hydantoin are reacted with NO2 gas under similar conditions depend on the temperature of the reaction. At 20 degrees C, a nitrated product is formed, but at 65 degrees C this gives way to a product containing no nitro groups. The findings show the general applicability of infrared microspectroscopy to a study of gas-solid reactions of organic single crystals.     

2-甲基-N-[4-硝基-3-三氟(甲基)苯基]丙酰胺的改进合成

以3－三氟里基苯为原料,在吸酸剂碳酸氢钠作用下与2－甲基丙酰氯反应得到2－甲基－N－[4－硝基－3－三氟（甲基）苯基]丙酰胺,再进行混酸硝化得到目标化合物。     

Nitro- and amino-substituted 10,10-dimethyl-10-sila-2-azaanthrones

Under conditions of the Mencke reaction, 10,10-dimethyl-9,10-dihydro-10-sila-2-azaanthracene is nitrated on the benzene fragment of the molecule, but the corresponding ketone is nitrated on the pyridine fragment. Dihydrosilaazaanthrone is nitrated by nitrating mixture in positions 5, 7, and 8 of the benzene fragment of the molecule. The nitro-substituted dihydrosilazaanthrones have been reduced to the corresponding amino derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1528–1531, November, 1985.     

Kinetic Modelling of the Concentrations of the Stabilizer DPA and Some of Its Consecutive Products as Function of Time and Temperature

By kinetic modelling of the possible reactions of diphenylamine (DPA) and its nitrated consecutive products used to stabilize cellulose nitrate (CN), one can get reactivities for the nitrated DPA compounds for the situation inside a real CN formulation and therewith determine their stabilizing contribution. Concentration data of DPA and seven of its consecutive products have been determined by HPLC from isothermal ageing of a CN formulation at temperatures between 65 and 90°C for up to 344 days. A comparison between the modelling presented and modellings published in the literature using the steady-state approximation is made. The steady-state approximation oversimplifies the stabilizer reaction behaviour in a CN formulation. From the applied modelling the question about N—NO—DPA as a key intermediate can be answered.This revised version was published online in November 2005 with corrections to the Cover Date.     

New heteroaromatic compounds—IV The nitration and chlorination of 10-methyl-10:9- borazarophenanthrene

10-Methyl- and 10-hydroxy-10:9-borazarophenanthrene have been nitrated with nitric acid in acetic anhydride, and the former compound has been chlorinated with chlorine in acetic acid; the products have been oriented and the proportions of isomers determined quantitatively. The results are shown to be in general agreement with the predictions of MO theory, attack taking place in the 6- and 8-positions. A method for degrading such boron compounds is described, and also the synthesis of 2-, 6-, and 8-chloro-10-methyl-10:9-borazarophenanthrenes as reference compounds. The 6- and 8-amino derivatives of 10-methyl and 10-hydroxy-10:9-borazarophenanthrene have been prepared by reduction of the corresponding nitro derivatives.     

Synthesis and characterization of the arylomycin lipoglycopeptide antibiotics and the crystallographic analysis of their complex with signal peptidase

Glycosylation of natural products, including antibiotics, often plays an important role in determining their physical properties and their biological activity, and thus their potential as drug candidates. The arylomycin class of antibiotics inhibits bacterial type I signal peptidase and is comprised of three related series of natural products with a lipopeptide tail attached to a core macrocycle. Previously, we reported the total synthesis of several A series derivatives, which have unmodified core macrocycles, as well as B series derivatives, which have a nitrated macrocycle. We now report the synthesis and biological evaluation of lipoglycopeptide arylomycin variants whose macrocycles are glycosylated with a deoxy-α-mannose substituent, and also in some cases hydroxylated. The synthesis of the derivatives bearing each possible deoxy-α-mannose enantiomer allowed us to assign the absolute stereochemistry of the sugar in the natural product and also to show that while glycosylation does not alter antibacterial activity, it does appear to improve solubility. Crystallographic structural studies of a lipoglycopeptide arylomycin bound to its signal peptidase target reveal the molecular interactions that underlie inhibition and also that the mannose is directed away from the binding site into solvent which suggests that other modifications may be made at the same position to further increase solubility and thus reduce protein binding and possibly optimize the pharmacokinetics of the scaffold.     

The aqueous phase nitration of phenol and benzoic acid studied through flow-gated capillary electrophoresis

The aqueous phase nitration of benzoic acid and phenol was investigated via on-line capillary electrophoresis (CE). The presence of nitrated benzoic acid and phenol was supported through appearance of corresponding molecular ion peaks in ESI-MS measurements, and speciation of the nitrated isomers is achieved via the on-line CE method. The nitrated isomers produced in both reactions were successfully separated in <4?min by addition of 15?mM β-cyclodextrin to the electrophoresis buffer. Sequential separations (on-line analysis) allowed the reaction kinetics to be described. For benzoic acid, reaction yields were low (2–3%) however, results suggest both 3- and 2-nitrobenzoic acid form in a 1–1.4 concentration ratio. In addition, 3-hydroxybenzoic acid also forms in significant quantity under our reaction conditions. For the nitration of phenol, the reaction occurred more rapidly with observed yields between ≈10–30% for individual isomers. The yield of 2-nitrophenol was higher than 4-nitrophenol by a ratio of ≈?1.7–2, but 3-nitrophenol was not detected. For both reactions, nitrated and hydroxylated aromatics were the major products and formation of higher molecular weight oligomers was not observed.     

Chemical Modification of β-Cyclodextrins: Balancing Soft and Rigid Domains in Complex Structures

Crystalline polymers such as β-cyclodextrin (βCD) can be modified with polyethylene glycol (PEG) diglycidyl ether cross-linkers (262, 394, 500 Da). In this work, the authors show that the quantity and length of the PEG soft segments influence the solubility and malleability of the products, which are water soluble and easily converted to nitrated analogues under standard reaction conditions. Inert and nitrated derivatives containing longer PEG segments showed the ability to self-heal. The degree of cross-linking and decomposition temperatures and energies depended on the quantity and length of the soft segment. Nitrated cross-linked βCD containing longer PEG segments did not ignite following an electrostatic discharge of 4.5 J. The chemical stability of βCD/PEG binders was tested by heat flow calorimetry at 80 °C. The balanced incorporation of soft PEG and rigid βCD segments was found to improve the processability of cross-linked βCDs and desensitised their nitrated derivatives, offering new solutions for inert and energetic binders.     

Comparison of fluorescence reagents for simultaneous determination of hydroxylated phenylalanine and nitrated tyrosine by high-performance liquid chromatography with fluorescence detection

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well-known and important contributors to oxidative and nitrosative stress in several diseases. Hydroxylated phenylalanine and nitrated tyrosine products appear to be particularly susceptible targets of oxidative and nitrosative stress. We compared fluorescence reagents for their potential use in the analysis of hydroxylated phenylalanine and nitrated tyrosine products with a high-sensitivity and high-specificity HPLC-UV-FL technique. The analytes were extracted from serum via solid-phase extraction on Waters Oasis MCX cartridges. Chromatographic separation was achieved on an ODS column (Capcell Pak MG II; 150 × 2.0 mm) using a gradient mobile phase consisting of 20 mm sodium phosphate buffer (adjusted to pH 3.0) and acetonitrile. The method quantification limit for 4-nitrophenylalanine, m-tyrosine, and 3-nitrotyrosine was 0.1 μm. The relative standard deviation of the precision and accuracy was acceptable at the spiked concentration of 0.1 μm for 4-nitrophenylalanine, m-tyrosine and 3-nitrotyrosine. The method could be used for the in vitro analysis of serum samples.     

Photochemical generation of nitric oxide from 6-nitrobenzo[a]pyrene

Photolabile 6-nitrobenzo[a]pyrene (6-nitroBaP) released nitric oxide (NO) under visible-light irradiation. The generation of NO and the concomitant formation of the 6-oxyBaP radical were confirmed by ESR. BaP quinones were also detected as further oxidized products of the 6-oxyBaP radical. No such photodegradation was observed with other nitrated BaPs, such as 1-nitroBaP and 3-nitroBaP. DNA-strand breakage, caused by photoexcited 6-nitroBaP, was closely related to its NO-releasing activity. MO calculations of nitrated BaP suggest that the perpendicular conformation of the nitro substituent to the aromatic ring is important for the release of NO with light. These findings may be useful for the development of a new type of NO donor.     

Nitration of 7- and 8-methyl-4-R-1H-2, 3-dihydro-1,5-benzodiazepin-2-ones

4-R-8-Methyl-2,3-dihydro-1H-1,5-benzodiazepin-2-ones are nitrated in the 7 position, whereas their 7-methyl analogs are nitrated in the 1, 8, or 9 position. The nitration of 4,8-dimethyldihydrobenzodiazepinone proceeds as primary substitution at the N₁ atom of the amide group. The resulting N₁-nitroamide undergoes prototropic rearrangement to the 9-nitro isomer in strongly acidic media.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 122–126, January, 1978.     

Electrolysis of Nitro Compound Salts: Application in Ketone Synthesis

One-pot electrochemical method of synthesis of ketones, diketones, and esters of monoketo- and diketoalkanoic acids is elaborated. This method is based on the diaphragmless galvanostatic electrolysis of Na salts of secondary nitro compounds—derivatives of nitrohydrocarbons, nitroketones, and esters of nitrated alkanoic acids—in methanol.     

Detection of explosives via photolytic cleavage of nitroesters and nitramines

The nitramine-containing explosive RDX and the nitroester-containing explosive PETN are shown to be susceptible to photofragmentation upon exposure to sunlight. Model compounds containing nitroester and nitramine moieties are also shown to fragment upon exposure to UV irradiation. The products of this photofragmentation are reactive, electrophilic NO(x) species, such as nitrous and nitric acid, nitric oxide, and nitrogen dioxide. N,N-Dimethylaniline is capable of being nitrated by the reactive, electrophilic NO(x) photofragmentation products of RDX and PETN. A series of 9,9-disubstituted 9,10-dihydroacridines (DHAs) are synthesized from either N-phenylanthranilic acid methyl ester or a diphenylamine derivative and are similarly shown to be rapidly nitrated by the photofragmentation products of RDX and PETN. A new (turn-on) emission signal at 550 nm is observed upon nitration of DHAs due to the generation of fluorescent donor-acceptor chromophores. Using fluorescence spectroscopy, the presence of ca. 1.2 ng of RDX and 320 pg of PETN can be detected by DHA indicators in the solid state upon exposure to sunlight. The nitration of aromatic amines by the photofragmentation products of RDX and PETN is presented as a unique, highly selective detection mechanism for nitroester- and nitramine-containing explosives and DHAs are presented as inexpensive and impermanent fluorogenic indicators for the selective, standoff/remote identification of RDX and PETN.     

Carbonate phobic (Zn,Mn)-Al hydrotalcite-like compounds

The synthesis method of three series of nitrated (Zn,Mn)-Al hydrotalcites in the presence of microwave irradiation is presented. MnO₄⁻ anions were partially incorporated between the layers of those compounds and a staged intercalation occurred. In the presence of CO₂, nitrated and permanganate intercalated hydrotalcites were tested in CO₃²⁻ retention. Carbonate phobic character was observed and it may be correlated to the poor basicity of hydrotalcites, thus, to the electronegativity of M²⁺ cations.