Two-dimensional Correlation NMR Spectroscopy Research Articles

A NOVEL METHOD FOR THE SYNTHESIS OF PYRIDO[1,2- b ][2]BENZAZEPINES ON THE BASIS OF 2-(BROMOMETHYL)BENZOPHENONES AND 2-(BROMOMETHYL)BENZALDEHYDE

A novel method for the synthesis of pyrido[1,2- b ][2]benzazepine derivatives is based on the reaction of 2-(bromomethyl)benzophenones and 2-(bromomethyl)benzaldehyde with 2-methylpyridines. The route of synthesis of 6 H -pyrido[1,2- b ][2]benzazepinium salts includes several steps with the possibility of isolating intermediate 1-benzyl-2-methylpyridinium and 11-aryl-11-hydroxy-11,12-dihydro-6 H- pyrido[1,2- b ][2]benzazepinium bromides. The efficiency of dehydration of intermediate carbinols increases with the use of protic solvents, an increase in heating time, and in the presence of electron-withdrawing substituents in the benzazepine moiety. The structure of the reaction products was proved by mass spectrometry, IR and one- and two-dimensional correlation NMR spectroscopy.

A novel method for the synthesis of pyrido[1,2-b][2]benzazepines on the basis of 2-(bromomethyl)benzophenones and 2-(bromomethyl)benzaldehyde

A novel method for the synthesis of pyrido[1,2-b][2]benzazepine derivatives is based on the reaction of 2-(bromomethyl)benzophenones and 2-(bromomethyl)benzaldehyde with 2-methylpyridines. The route of synthesis of 6H-pyrido[1,2-b][2]benzazepinium salts includes several steps with the possibility of isolating intermediate 1-benzyl-2-methylpyridinium and 11-aryl-11-hydroxy-11,12-dihydro-6Hpyrido[1,2-b][2]benzazepinium bromides. The efficiency of dehydration of intermediate carbinols increases with the use of protic solvents, an increase in heating time, and in the presence of electron-withdrawing substituents in the benzazepine moiety. The structure of the reaction products was proved by mass spectrometry, IR and one- and two-dimensional correlation NMR spectroscopy.

Pyrano[3,4-c]pyrandiium dication

Pyrano[3,4-c]pyrandiium dication has been detected in anhydrous D2SO4 using two-dimensional correlation NMR spectroscopy. The dication is generated as an intermediate in acid-catalyzed hydrolysis of 1-ethoxy-5-methyl-3,8-diphenyl-1H-pyrano[3,4-c]pyran-7-ium perchlorate, where the action of 70% HClO4 leads to the replacement of ethoxy group by hydroxyl one, and the reaction with SbCl5 affords dimeric bis(hexachloroantimonate) bearing two pyrano[3,4-c]pyran7-ium moieties linked via oxygen atom. The crystal structures of both isolated products have been determined.

SYNTHESIS AND STRUCTURE OF NEW DERIVATIVES OF 10-R-4-METHYL-1,8-DINITRO-3-OXA-5,10-DIAZATRICYCLO[6.3.1.02.6]DODECA-2(6),4-DIENE

The spatial and electronic structure of 2-methyl-5,7-dinitrobenzo[d]oxazole, which is the substrate for the synthesis of hydride σ-adducts, was studied by the DFT/B3LYP/aug-cc-pVDZ method. Analysis of the charges on the atoms showed that the largest positive NBO charge is concentrated on the carbon atom C2 of the oxazole ring, while the carbon atoms C4 and C6 annelated benzene nucleus have the highest Mulliken charges both in the gas phase and in water. Thus, it has been established that a rigid base, a methoxide ion, is attached to the carbon atom C2, which is a hard reaction center, and a reaction with a soft base, a hydride ion, can also proceed through softer reaction centers — carbon atoms of the benzene ring C4 and C6. The bond lengths calculated by the quantum-chemical method are in good agreement with the experimental data obtained by X-ray diffraction, which confirms the correctness of the choice of the quantum-chemical calculation method. New derivatives of 3-azabicyclo [3.3.1]nonane have been synthesized by Mannich condensation of 2-methyl-5,7-dinitrobenzo[d]oxazole hydride σ-adduct with methylamine and β-aminopropanoic acid. This method is distinguished by relative simplicity, availability of reagents and allows under mild conditions to transfer from the aromatic system activated by nitro groups to 3-azabicyclo[3.3.1]nonane derivatives containing the nitro groups that are promising from the point of view of further functionalization. The structure of the compounds obtained was proved by IR, 1H-, 13C-, two-dimensional correlation NMR spectroscopy, as well as elemental analysis data. It was shown that the compounds obtained can serve as the basis for the creation of hybrid physiologically active compounds containing both a 3-azabicyclononane fragment and an oxazole cycle.

Синтез и строение новых производных 2-хлор-N-(3-R-1,5-динитро-8-оксо-3-азабицикло[3.3.1]нон-6-ен-7-ил)ацетамидов

The production of new 3-azabicyclononane derivatives is an important trend in the synthesis of organic compounds. It is known that 3-azabicyclononane is a key pharmacophore of a number of plant alkaloids that are widely used in medicine (aconitin, quinidine, tropane, cocaine, garnet, etc.). Among synthetic heterocycles containing a 3-azabicyclo[3.3.1]nonane fragment, compounds with various types of biological activity were found: analgesic and anti-inflammatory, antimicrobial and fungicidal, anti-cancer, antioxidant, etc. We synthesized a number of new derivatives of 3-azabicyclo[3.3. 1]nonane by Mannich condensation of hydride σ-adduct 2-chloro-N-(2-hydroxy-3,5-dinitrophenyl)acetamide with formaldehyde and primary amines or amino acids. The synthesis was carried out in two stages. In the first stage, under the action of sodium tetrahydride borate on a solution of 2-chloro-N-(2-hydroxy-3,5-dinitrophenyl)acetamide, the C=C bonds of the aromatic ring were reduced to form a 3-charge hydride adduct. The resulting diaduct was isolated from the solution and, while cooling with ice, was introduced into Mannich condensation with formaldehyde and a solution of the primary amine or amino acid. When the reaction mixture was acidified with dilute orthophosphoric acid to pH 4-5, precipitates of the target products precipitated. After recrystallization from ethanol, the yield of the target products, depending on the substituent at the nitrogen atom, was 75-90%. This method is distinguished by relative simplicity, availability of reagents and allows under mild conditions to transfer from the aromatic system activated by nitro groups to 3-azabicyclo[3.3.1]nonane derivatives, containing promising from the point of view of further functionalization nitro, carbonyl, amino groups, and also halogen atom . The structure of the compounds obtained was proved by IR, 1H-, 13C-, two-dimensional correlation NMR spectroscopy, as well as high-resolution mass spectrometry data (HRMS).

SYNTHESIS OF NEW DERIVATIVES OF 3-AZABICYCLO[3.3.1]NONANES BASIS ON N-(2-HYDROXY-3,5-DINITROPHENYL)ACETAMIDE σ-ADDUCT

A number of new derivatives of N-(3-R-1,5-dinitro-8-oxo-3-azabicyclo[3.3.1]non-6-en-7-yl)acetamides have been synthesized by Mannich condensation of hydride σ-adduct of the N-(2-hydroxy-3,5-dinitrophenyl)acetamide with formaldehyde and primary amines. The synthesis was carried out with two stages. In the first stage, under the action of sodium tetrahydride borate on a solution of N-(2-hydroxy-3,5-dinitrophenyl)acetamide, the C = C bonds of the aromatic ring were reduced to form a 3-charge hydride adduct. The resulting diaduct was isolated from the solution and, while cooling with ice, was introduced into Mannich-condensation with formaldehyde and a solution of the primary amine or amino acid. When the reaction mixture was acidified with dilute orthophosphoric acid to pH 4–5, precipitates of the target products precipitated. After recrystallization from ethanol, the yield of the target products, depending on the substituent at the nitrogen atom, ranged from 55 to 90%. This method is distinguished by relative simplicity, availability of reagents and allows under mild conditions to transfer from the aromatic system activated by nitro groups to 3-azabicyclo[3.3.1]nonane derivatives, containing promising from the point of view of further functionalization nitro, carbonyl and amino groups. The structure of the compounds obtained was proved by IR, 1H-, 13C-, two-dimensional correlation NMR spectroscopy, as well as elemental analysis data. In the IR spectra of the obtained substances, the characteristic absorption bands of amide I (1629-1633 cm-1) and amide II (1560-1570 cm-1), as well as antisymmetric (1549-1556 cm-1) and symmetric (1370-1377 cm-1) oscillations of nitro groups were observed. In the NMR spectra in the weakest field, the broadened signal of the proton NH is observed (δ 9.51-9.57 ppm), followed by the singlet signal of the proton at the double bond (δ 8.15-8.16 ppm). The protons of the methylene groups of the bicyclic system are diastereotopic. Therefore, their signals are mutually split into broadened doublets located in the region of 2.66–3.46 ppm.

Synthesis and structural studies of 5,7(4,6)-di(tert-butyl)-2-(6,8-dimethyl-4-chloroquinolin-2-yl)-1,3-tropolones by quantum-chemical methods and two-dimensional correlation NMR spectroscopy

4,6-Di(tert-butyl)-2-(quinolin-2-yl)-1,3-tropolone (7′) was isolated for the first time from the acid-catalyzed reaction of 2-methyl-substituted nitrogen heterocycles with 1,2-benzoquinones, which proceeds with the expansion of the o-quinone ring to give mainly isomeric 5,7-di(tert-butyl)-2-(quinolin-2-yl)-1,3-tropolone.

Proton–nitrogen-14 overtone two-dimensional correlation NMR spectroscopy of solid-sample at very fast magic angle sample spinning

1H–14N overtone (OT) heteronuclear multiple quantum coherence (HMQC) experiment at very fast magic angle spinning (MAS) is reported. The 14N OT coherence is excited and reconverted by 14N OT pulses at twice the 14N Larmor frequency. The OT coherence is free from the first order quadrupolar broadening. MAS further removes the broadening due to chemical shift anisotropy (CSA). With a small 0.75mm MAS rotor and coil system, very fast MAS up to 90kHz and very strong rf field are achieved, enhancing the sensitivity of indirect 14N OT observation via protons. In comparison with 1H–14N double-quantum HMQC, an enhancement factor of 1.8 is obtained for glycine with the 14N OT irradiation. The bandwidth in the 14N OT dimension is limited due to long 14N OT pulses.

Structure of a rosin–itaconic acid adduct from 2D NMR spectroscopy data

We have used two-dimensional correlation NMR spectroscopy to study the structure of a new derivative of resin acids isolated from a rosin–itaconic acid adduct. We have established that the synthesized compound is the product of addition of citraconic anhydride to levopimaric acid, the structure of which is close to the structure of maleopimaric acid.

1,N2-propanodeoxyguanosine adducts of the 1,3-butadiene metabolite, hydroxymethylvinyl ketone.

1,3-Butadiene (BD) is a rodent and human carcinogen. While several epoxides formed during BD metabolism are mutagenic and may contribute to BD carcinogenicity, another proposed metabolite, hydroxymethylvinyl ketone (HMVK), could also be involved. A significant quantity of HMVK is likely to be formed since it is a proposed intermediate in the metabolism of 3-butene-1,2-diol (BD-diol) to 1,2-dihydroxy-4-(N-acetylcysteinyl)butane, the major mercapturic acid metabolite of BD in humans. In addition, BD-diol is a major BD metabolite in liver perfusion experiments in rodents. By analogy with other alpha,beta-unsaturated carbonyls, HMVK is likely to be mutagenic via formation of promutagenic 1,N(2)-propanodeoxyguanosine adducts. The objective of the current study was to investigate the formation of such adducts in vitro. The reaction between HMVK and dGuo yielded two major products shown to be identical by positive ion electrospray-MS, having protonated molecular ions with m/z consistent with HMVK-derived 1,N(2)-propanodeoxyguanosine (HMVK-dGuo). Rechromatography of each fraction yielded two fractions with retention times identical to those initially isolated, suggesting equilibration between two diastereomers. Two partially resolved sets of (1)H NMR signals were consistent with a 1:1 mixture of diastereomeric C-6-substituted adducts equilibrating slowly on an NMR time-scale. Following deglycosylation, C-6 substitution was verified by two-dimensional correlation NMR spectroscopy, indicating that the initial adducts were formed by Michael addition of dGuo-N1 to the terminal vinyl carbon followed by cyclization to the 1,N(2)-propano structure. Reactions with calf thymus DNA under physiological conditions yielded two sets of products. The first set had HPLC retention times and mass spectra identical to those of the previously characterized C-6-substituted HMVK-dGuo diastereomers. The second set had a molecular ion and fragmentation pattern identical to the C-6-substituted adducts and on this basis were assigned as the diastereomeric C-8 adducts. In addition to detecting HMVK-dGuo in treated DNA, the adducts were also present in control DNA. Overall, our research demonstrates that HMVK can form promutagenic DNA adducts and it therefore has the potential to play a role in BD-associated mutagenicity.

Synthesis and characterization of peptides containing a cyclic Val adduct of diepoxybutane, a possible biomarker of human exposure to butadiene.

1,3-Butadiene, a potential human carcinogen widely used in industry, is oxidized by cytochrome P450 to diepoxybutane (DEB), which is the most mutagenic of the known butadiene metabolites. Assessment of the toxicological significance of DEB formation in humans and animals requires identification of a biomarker uniquely associated with DEB for use in molecular dosimetry studies. We wished to develop a specific and sensitive assay for one such suitable marker, the cyclic adduct 2-(3,4-dihydroxypyrrolidin-1-yl)-3-methylbutyramide (pyr-V), which is formed from addition of DEB to the terminal Val of the alpha- and beta-chains of hemoglobin. We needed to prepare a pure, rigorously characterized DEB-modified N-terminal oligopeptide for raising antibodies both to use in an immunoaffinity purification step and to standardize the assay. In addition, we needed a pure isotopomer to serve as an internal standard for quantitation by LC-MS. Direct modification of the globin sequences by reaction with DEB in vitro proved to be unproductive. We therefore opted to synthesize the cyclic Val adduct and incorporate it by FMOC chemistry into the appropriate oligopeptide sequences. In vitro and in vivo, butadiene is oxidized to enantiomeric and meso forms of DEB. A priori, all three DEB isomers are expected to form pyr-V adducts, resulting in three diastereomeric N-terminal peptides. We therefore synthesized a mixture of the cyclic Val diastereomers as their methyl esters by reaction of DEB with l-Val methyl ester hydrochloride. After protection as the di-O-tert-butyl derivatives, the mixture of 2-(3,4-di-t-butoxypyrrolidin-1-yl)-3-methylbutyric acid diastereomers was incorporated as the N-terminal residue into the 1-11 human globin alpha-chain sequence VLSPADKTNVK. The presence of the three diastereomers was confirmed by two-dimensional correlation NMR spectroscopy and temperature-dependent (1)H NMR. This strategy enabled us to obtain pure, rigorously characterized haptens in quantity for the preparation of polyclonal antibodies. Use of FMOC-protected (2)H(3)-Leu in the automated oligopeptide synthesis provided the required isotopomers for use as internal standard.

Multiple-quantum-filtered two-dimensional correlated NMR spectroscopy of proteins

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMultiple-quantum-filtered two-dimensional correlated NMR spectroscopy of proteinsNorbert. Mueller, Richard R. Ernst, and Kurt. WuethrichCite this: J. Am. Chem. Soc. 1986, 108, 21, 6482–6492Publication Date (Print):October 1, 1986Publication History Published online1 May 2002Published inissue 1 October 1986https://doi.org/10.1021/ja00281a006RIGHTS & PERMISSIONSArticle Views224Altmetric-Citations122LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (2 MB) Get e-Alerts Get e-Alerts

Sequence of δ-carbon signals in 2-substituted adamantanes determined by two-dimensional correlated NMR spectroscopy

The δ-carbon resonances of 23 2-substituted adamantanes mere assigned unequivocally by two-dimensional (2D) correlated NHR spectroscopy. It is shown that in contrast to all previously published instances the δ carbon signal sequence is reversed for 10 other substituents.

Spin multiplet enhancement in two-dimensional correlated NMR spectroscopy

Methode puissante pour deceler les couplages homonucleaires dans des molecules de poids moleculaire tres eleve. Exemple avec l'amphotericine B