The “Speedy” Synthesis of Atom‐Specific 15N Imino/Amido‐Labeled RNA

Although numerous reports on the synthesis of atom‐specific ¹⁵N‐labeled nucleosides exist, fast and facile access to the corresponding phosphoramidites for RNA solid‐phase synthesis is still lacking. This situation represents a severe bottleneck for NMR spectroscopic investigations on functional RNAs. Here, we present optimized procedures to speed up the synthesis of ¹⁵N(1) adenosine and ¹⁵N(1) guanosine amidites, which are the much needed counterparts of the more straightforward‐to‐achieve ¹⁵N(3) uridine and ¹⁵N(3) cytidine amidites in order to tap full potential of ¹H/¹⁵N/¹⁵N‐COSY experiments for directly monitoring individual Watson–Crick base pairs in RNA. Demonstrated for two preQ₁ riboswitch systems, we exemplify a versatile concept for individual base‐pair labeling in the analysis of conformationally flexible RNAs when competing structures and conformational dynamics are encountered.     

Solid‐State NMR Investigations on the Amorphous Network of Precursor‐Derived Si2B2N5C4 Ceramics

Employing a multitude of modern solid state NMR techniques including ¹³C{¹⁵N}REDOR NMR, ¹H–¹³C CP NMR, ¹¹B MQMAS NMR spectroscopic experiments, the structural organization of Si₂B₂N₅C₄ ceramic has been studied. The experiments were executed on double isotope enriched (¹³C, ¹⁵N) and natural isotope abundance Si₂B₂N₅C₄ ceramics. The materials were synthesized by aminolysis and subsequent pyrolysis of intermediate pre‐ceramic polymers that were obtained from the single source precursor TSDE, 1‐(trichlorosilyl)‐1‐(dichloroboryl)ethane (Cl₃Si–CH(CH₃)–BCl₂). The result of the ¹³C{¹⁵N} REDOR NMR spectroscopic experiment shows that carbon atoms are incorporated into the network by bridging to nitrogen, which already occurs during the polymerization step. Furthermore, the combined results of ¹¹B NMR and ¹¹B MQMAS NMR indicate that boron atoms may also be connected to carbon in addition to nitrogen.     

1H, 13C and 15N NMR spectroscopic characterization of unexpected degradation products of the nifedipine analogue bis(2‐cyanoethyl) 2,6‐dimethyl‐4‐(2‐nitrophenyl)‐1,4‐dihydro‐3,5‐pyridinedicarboxylate

In the course of saponification experiments with bis(2‐cyanoethyl) 2,6‐dimethyl‐4‐(2‐nitrophenyl)‐1,4‐dihydro‐3,5‐pyridinedicarboxylate ( 1 ), an analogue of the calcium channel blocker nifedipine, three unexpected degradation products were isolated. The compounds were identified as 3‐(2‐acetamido‐1‐carboxy‐1‐propenyl)‐1‐hydroxy‐2‐indolecarboxylic acid ( 3 ), 9‐hydroxy‐1,3‐dimethyl‐β‐carboline‐4‐carboxylic acid ( 4 ) and 6‐hydroxy‐2,4‐dimethyl‐5‐oxo‐5,6‐dihydrobenzo[c][2,7]naphthyridine‐1‐carboxylic acid ( 6 ). The structures of these compounds were deduced from one‐ and two‐dimensional ¹H, ¹³C and natural abundance ¹⁵N NMR experiments (¹H,¹H‐COSY, gs‐HSQC, gs‐HMBC, ¹⁵N gs‐HMBC), and corroborated by comparison of their NMR data with the respective data for structurally similar compounds. Copyright © 2002 John Wiley & Sons, Ltd.     

Chemoselective detection and discrimination of carbonyl‐containing compounds in metabolite mixtures by 1H‐detected 15N nuclear magnetic resonance

NMR spectra of mixtures of metabolites extracted from cells or tissues are extremely complex, reflecting the large number of compounds that are present over a wide range of concentrations. Although multidimensional NMR can greatly improve resolution as well as improve reliability of compound assignments, lower abundance metabolites often remain hidden. We have developed a carbonyl‐selective aminooxy probe that specifically reacts with free keto and aldehyde functions, but not carboxylates. By incorporating ¹⁵N in the aminooxy functional group, ¹⁵N‐edited NMR was used to select exclusively those metabolites that contain a free carbonyl function while all other metabolites are rejected. Here, we demonstrate that the chemical shifts of the aminooxy adducts of ketones and aldehydes are very different, which can be used to discriminate between aldoses and ketoses, for example. Utilizing the 2‐bond or 3‐bond ¹⁵N‐¹H couplings, the ¹⁵N‐edited NMR analysis was optimized first with authentic standards and then applied to an extract of the lung adenocarcinoma cell line A549. More than 30 carbonyl‐containing compounds at NMR‐detectable levels, six of which we have assigned by reference to our database. As the aminooxy probe contains a permanently charged quaternary ammonium group, the adducts are also optimized for detection by mass spectrometry. Thus, this sample preparation technique provides a better link between the two structural determination tools, thereby paving the way to faster and more reliable identification of both known and unknown metabolites directly in crude biological extracts. Copyright © 2015 John Wiley & Sons, Ltd.     

NMR study of spirophosphoranes derived from 2‐aminophenols

Multinuclear magnetic resonance experiments were performed (¹H, ¹³C, ³¹P, and ¹⁵N) for P‐H phosphoranes derived from 2‐aminophenol, 4‐tert‐butyl‐2‐aminophenol, and 4,6‐di‐tert‐butyl‐2‐aminophenol. Selective heteronuclear ¹H{¹⁵N} double resonance experiments and two‐dimensional ¹⁵N/¹H HETCOR experiments enabled us to determine various signs of coupling constants (e.g., ²J(³¹P, N, ¹H) > 0; ¹J(³¹P, ¹⁵N) < 0). The ¹H‐coupled ¹⁵N NMR spectrum recorded by the INEPT pulse sequence shows the splitting due to ¹J(³¹P, ¹⁵N) and ²J(¹⁵N, P, ¹H). The latter value is useful for polarization transfer experiments from ¹H to ¹⁵N, once the hydrogen atoms of the N‐H functions are replaced by other groups. Isotope‐induced chemical shifts ¹Δ^14/15N(³¹P) were measured by using the INEPT‐HEED pulse sequence. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:11–15, 2000     

N7‐ and N9‐substituted purine derivatives: a 15N NMR study

The ¹⁵N NMR chemical shifts of N⁷‐ and N⁹‐substituted purine derivatives were investigated systematically at the natural abundance level of the ¹⁵N isotope. The NMR chemical shifts were determined and assigned using GSQMBC, GHMBC, GHMQC and GHSQC experiments in solution. ¹⁵N cross‐polarization magic angle spinning data were recorded for selected compounds in order to study the principal values of the ¹⁵N chemical shifts. Geometric parameters obtained by using RHF/6–31G** and single‐crystal x‐ray structural analysis were used to calculate the chemical‐shielding constants (GIAO and IGLO) which were then used to assign the nitrogen resonances observed in the solid‐state NMR spectra and to determine the orientation of the principal components of the shift tensors. Copyright © 2002 John Wiley & Sons, Ltd.     

Recyclizations of 2‐aminobenzylimines and thioaroylhydrazones of N‐substituted N‐hydroxy‐3‐oxobutanamides

A universal scheme is proposed for the molecular design of heterocyclic recyclizations by replacing the exocyclic hydroxyl groups in exo‐trig‐ ring‐chain tautomeric molecules with substituted amines or hydrazines. The practical applicability of this approach is demonstrated by the condensations of 5‐hydroxy‐5‐methyl‐3‐isoxazolidinones with thioaroyl‐hydrazines and 2‐aminomethylaniline. The condensation products were studied by modern ¹H, ¹³C and ¹⁵N NMR spectroscopic methods using three solvents: CDC1₃, DMSO[D₆] and CD₃CN. The solvent was found to have a strong effect to the relative amounts of the tautomers.     

Heterocyclic analogs of xanthiones: 5,6‐fused 3‐methyl‐1‐phenylpyrano[2,3‐c]pyrazol‐4(1H) thiones—synthesis and NMR (1H, 13C, 15N) data

Various [5,6]pyrano[2,3‐c]pyrazol‐4(1H)‐thiones were synthesized in high yields by treatment of the corresponding [5,6]pyrano[2,3‐c]pyrazol‐4(1H)‐ones with Lawesson's reagent. Detailed NMR spectroscopic studies were undertaken of the title compounds. Complete and unambiguous assignment of chemical shifts (¹H, ¹³C, ¹⁵N) and coupling constants (¹H,¹H; ¹³C,¹H) was achieved by the combined application of various one‐ and two‐dimensional (1D and 2D) NMR spectroscopic techniques. Unequivocal mapping of most ¹³C,¹H spin coupling constants is accomplished by 2D (δ, J) long‐range INEPT spectra with selective excitation. Copyright © 2010 John Wiley & Sons, Ltd.     

Thiol–thione tautomeric forms recognition on the example of 4‐[3‐(2‐methyl‐furan‐3‐yl)‐5‐thioxo‐1,2,4‐triazolin‐4‐yl]acetic acid

The synthesis of 4‐[3‐(2‐methyl‐furan‐3‐yl)‐5‐thioxo‐1,2,4‐triazolin‐4‐yl]acetic acid, its structural study in the solid state, and the thiol–thione tautomeric recognition on the basis of spectroscopic data and theoretical calculations are presented. It is shown that NMR spectra, especially ¹³C and ¹⁵N, are indicative of the actual tautomeric form whereas vibrational data can be ambiguous. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:337–344, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20433     

Characterization of 2‐aryl‐1,3,4‐oxadiazoles by 15N and 13C NMR spectroscopy

¹⁵N NMR chemical shifts of 2‐aryl‐1,3,4‐oxadiazoles were assigned on the basis of the ¹H–¹⁵N HMBC experiment. Chemical shifts of the nitrogen and carbon atoms in the oxadiazole ring correlate with the Hammett σ‐constants of substituents in the aryl ring (r² ≥ 0.966 for N atoms). ¹⁵N NMR data are a suitable and sensitive means for characterizing long‐range electronic substituent effects. Additionally, ¹³C NMR data for these compounds are presented. Copyright © 2003 John Wiley & Sons, Ltd.     

Pd‐Assisted Cross‐Coupling Reactions with 4‐Chlorocinnoline

A series of 4‐ethynylcinnolines 3a – e was prepared by Sonogashira reaction of 4‐chlorocinnoline ( 1 ) with appropriate alkynes. Moreover, Suzuki coupling of 1 with boronic esters gave the corresponding 4‐arylcinnolines 5a – c . Detailed NMR spectroscopic data including unambiguous chemical shift assignments of all ¹H, ¹³C, and ¹⁵N resonances of the obtained cinnoline derivatives are reported.     

Quantitative and qualitative 1H, 13C,and 15N NMR spectroscopic investigation of the urea–formaldehyde resin synthesis

Urea–formaldehyde resins are bulk products of the chemical industry. Their synthesis involves a complex reaction network. The present work contributes to its elucidation by presenting results from detailed NMR spectroscopic studies with different methods. Besides¹H NMR and¹³C NMR,¹⁵N NMR spectroscopy is also applied.¹⁵N‐enriched urea was used for the investigations. A detailed NMR signal assignment and a model of the reaction network of the hydroxymethylation step of the synthesis are presented. Because of its higher spectral dispersion and the fact that all key reactions directly involve the nitrogen centers,¹⁵N NMR provides a much larger amount of detail than do¹H and¹³C NMR spectroscopy. Symmetric and asymmetric dimethylol urea can be clearly distinguished and separated from monomethylol urea, trimethylol urea, and methylene‐bridged urea. The existence of hemiformals of methylol urea is confirmed. 1,3,5‐Oxadiazinan‐4‐on (uron) and its derivatives were not found in the reaction mixtures investigated here but were prepared via alternative routes. The molar ratios of formaldehyde to urea were 1, 2, and 4, the pH values 7.5 and 8.5, and the reaction temperature 60 °C. Copyright © 2014 John Wiley & Sons, Ltd.     

Syntheses and characterization of 2‐hydroxy‐N‐(2′‐hydroxyalkyl)acetamides

The reaction of glycolic acid 1 with some β‐aminoalcohols 2–8 without solvent, with temperature and time controlled, led to the syntheses of2‐hydroxy‐N‐(2′‐hydroxyalkyl)acetamides 9–15. All compounds studied in this work were characterized by ¹H, ¹³C, and ¹⁵N NMR, infrared, and mass spectroscopy. The structure of compound 13 was established by a single‐crystal X‐ray diffraction study. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 153–158, 1999     

1H and 13C NMR spectral data of bioactive cage‐like polycyclic compounds

Bioactive cage‐like polycyclic compounds have attracted the attention of several research groups because of their unique appearance and their biological activities. Their structures were established on the basis of ¹H NMR and ¹³C NMR spectroscopic data. The ¹H and ¹³C signal assignments and most homonuclear hydrogen coupling constants were assigned by use of techniques such as 1D ¹H and ¹³C NMR and 2D gCOSY, non‐edited gHSQC and gHMBC. The gNOESY experiments proved the endo‐stereochemistry. Copyright © 2010 John Wiley & Sons, Ltd.     

(+)‐(14β)‐14‐Ethylmatridin‐15‐one,a New Quinolizidine Alkaloid from the Poisonous Plant Oxytropis ochrocephala Bunge

A new matrine alkaloid derivative (+)‐(14β)‐14‐ethylmatridin‐15‐one ( 1 ) was isolated from the poisonous plant Oxytropis ochrocephala Bunge . The structure was established by spectroscopic methods, including extensive 1D‐ and 2D‐NMR experiments.     

7‐Azacinnolin‐4(1H)‐one preparation and NMR studies of tautomery

As part of our current investigations of nitropyridines, we hereby report the preparation of a new annulated heterocycle by C‐azo coupling. Thus, the azacinnoline, pyrido[3,4‐c]pyridazin‐4(1H)‐one (38%), was prepared from 4‐acetyl‐3‐aminopyridine via diazotization. ¹H, ¹³C, and ¹⁵N NMR spectroscopic investigations revealed that the azacinnoline exclusively exists in the NH‐keto tautomeric form in DMSO‐d₆, CD₃OD, and D₂O. J. Heterocyclic Chem., (2011).     

Acetone‐induced polymerisation of 3‐aminopropyltrimethoxysilane (APTMS) as revealed by NMR spectroscopy

We followed the reactivity of acetone with 3‐aminopropyltrimethoxysilane, a potential organosilane coupling agent, by ¹H, ¹³C and ²⁹Si NMR spectroscopy. Selective 1D and 2D‐edited NMR experiments significantly contributed to simplify the spectral complexity of reaction solution and elucidated molecular structures within progressive reaction phases. The course of the 3‐aminopropyltrimethoxysilane reaction with acetone was shown by a progressive decrease of both reactants, and a concomitant appearance of water and methanol, due to formation of imine and hydrolysis of alkoxysilane groups, respectively. The occurrence of multiple siloxane linkages in a progressively larger cross‐linked macromolecular structure was revealed by DOSY‐NMR experiments and new signals in ²⁹Si‐NMR spectra at different reaction times. The NMR approach described here may be applied to investigate the reactivity of other γ‐aminopropylalkoxysilanes and contribute to define procedures for the preparation of silica‐based materials. Copyright © 2014 John Wiley & Sons, Ltd.     

Protonation Behaviour of Chiral Tetradentate Polypyridines Derived from α‐Pinene

Detailed protonation experiments of the [5,6]‐pinenebipyridine molecule and the unsubstituted [4,5]‐ and [5,6]‐CHIRAGEN[0] ligands in various solvents indicate a variety of structures of the protonated species. UV‐visible and NMR measurements (including ¹⁵N chemical shifts) show the transition from trans to cis conformation of [5,6]‐pinenebipyridine upon protonation. The [4,5]‐CHIRAGEN[0] ligand, in which the protonation sites of the nitrogen atom donors are at opposite sides of the molecule, behave essentially like two independent bipyridine moieties; this behaviour was monitored by UV‐visible, CD and NMR spectroscopy (including ¹⁵N data). In the case of the [5,6]‐CHIRAGEN[0], a pocket of donor atoms provides a chiral environment for two protons per ligand.     

4,5‐Dihydro‐1,2,3‐oxadiazole: A Very Elusive Key Intermediate in Various Important Chemical Transformations

4,5‐Dihydro‐1,2,3‐oxadiazoles are postulated to be key intermediates in the industrial synthesis of ketones from alkenes, in the alkylation of DNA in vivo, and in the decomposition of N‐nitrosoureas; they are also a subject of great interest for theoretical chemists. In the presented report, the formation of 4,5‐dihydro‐1,2,3‐oxadiazole and the subsequent decay into secondary products have been studied by NMR monitoring analysis. The elusive properties evading characterization have now been confirmed by ¹H, ¹³C, and ¹⁵N NMR spectroscopy, and relevant 2D experiments at very low temperatures. Our experiments with suitably substituted N‐nitrosoureas using thallium(I) alkoxides as bases under apolar conditions answer important questions on the existence and the secondary products of 4,5‐dihydro‐1,2,3‐oxadiazole.     

Investigation of Some Functionalization Reactions of 4‐Benzoyl‐5‐phenyl‐1‐(4‐methoxyphenyl)‐1H‐pyrazole‐3‐carbonyl Chloride and Their Antimicrobial Activity

The 1H‐pyrazole‐3‐carboxylic acid 1 was converted via reactions of its acid chloride 3 with various asymmetrical disubstituted urea and alcohol derivatives into the corresponding novel 4‐benzoyl‐N‐(N′,N′‐dialkylcarbamyl)‐1‐(4‐methoxyphenyl)‐5‐phenyl‐1H‐pyrazole‐3‐carboxamide 4a , b and alkyl 4‐benzoyl‐1‐(4‐methoxyphenyl)‐5‐phenyl‐1H‐pyrazole‐3‐carboxylate 7a‐c , respectively, in good yields (57%‐78%). Friedel‐Crafts reactions of 3 with aromatic compouns for 15 min.‐2 h led to the formation of the 4‐3‐diaroyl‐1‐(4‐hydroxyphenyl)‐5‐phenyl‐1H‐pyrazoles 9a‐c , 4‐benzoyl‐1‐(4‐methoxyphenyl)‐3‐aroyl‐5‐phenyl‐1H‐pyrazoles 10a , b and than from the acylation reactions of 9a‐c were obtained the 3,4‐diaroyl‐1‐(4‐acyloxyphenyl)‐5‐phenyl‐1H‐pyrazoles 13a‐d . The structures of all new synthesized compounds were established by NMR experiments such as ¹H, and ¹³C, as well as 2D COSY and IR spectroscopic data, and elemental analyses. All the compounds were evaluated for their antimicrobial activities (agar diffusion method) against eight bacteria and two yeasts.