Synthesis and NMR spectra of the syn and anti isomers of substituted cyclobutanes—evidence for steric and spatial hyperconjugative interactions

The syn and anti isomers of cis,cis-tricyclo[5.3.0.0^2,6]dec-3-ene derivatives have been synthesized and their ¹H and ¹³C NMR spectra unequivocally analyzed. Both their structures and their ¹H and ¹³C NMR chemical shifts were calculated by DFT, the latter two calculations employing the GIAO perturbation method. Additionally, calculated NMR shielding values were partitioned into Lewis and non-Lewis contributions from the bonds and lone pairs involved in the molecules by accompanying NBO and NCS analyses. The differences between the syn and anti isomers were evaluated with respect to steric and spatial hyperconjugation interactions.     

Five new isocoumarins from Sonoran desert plant-associated fungal strains Paraphaeosphaeria quadriseptata and Chaetomium chiversii

Five new isocoumarins, paraphaeosphaerins A-C and chaetochiversins A and B, biogenetically related to monocillin I and radicicol, have been isolated from solid agar cultures of Paraphaeosphaeria quadriseptata and Chaetomium chiversii, two fungal strains living in association with the Sonoran desert plants, Opuntia leptocaulis and Ephedra fasciculata, respectively. A new chroman-4-one, aposphaerin C, was also isolated from P. quadriseptata. Their structures and stereochemistry were elucidated using a combination of ¹H and ¹³C homo- and hetero-nuclear 2D NMR techniques, ¹H NMR analysis of Mosher's esters, and chemical correlations.     

LC/ESI-MS n and 1H HR-MAS NMR analytical methods as useful taxonomical tools within the genus Cystoseira C. Agardh (Fucales; Phaeophyceae)

Species of the genus Cystoseira are particularly hard to discriminate, due to the complexity of their morphology, which can be influenced by their phenological state and ecological parameters. Our study emphasized on the relevance of two kinds of analytical tools, (1) LC/ESI-MSⁿ and (2) ¹H HR-MAS NMR, also called in vivo NMR, to identify Cystoseira specimens at the specific level and discuss their taxonomy. For these analyses, samples were collected at several locations in Brittany (France), where Cystoseira baccata, C. foeniculacea, C. humilis, C. nodicaulis and C. tamariscifolia were previously reported. To validate our chemical procedure, the sequence of the ITS2 has been obtained for each species to investigate their phylogenetic relationships at a molecular level. Our study highlighted the consistency of the two physico-chemical methods, compared to “classical” molecular approach, in studying taxonomy within the genus Cystoseira. Especially, LC/ESI-MSⁿ and phylogenetic analyses converged into the discrimination of two taxonomical groups among the 5 species. The occurrence of some specific signals in the ¹H HR-MAS NMR spectra and/or some characteristic chemical compounds during LC/ESI-MSⁿ analysis could be regarded as discriminating factors. LC/ESI-MSⁿ and ¹H HR-MAS NMR turned out to be two relevant and innovative techniques to discriminate taxonomically this complex genus.     

Quinoxalines XIV. Synthesis, H, C, N NMR spectroscopic, and quantum chemical study of 1H-pyrazolo[3,4-b]quinoxalines (flavazoles)

The synthesis of a series of 1H-pyrazolo[3,4-b]quinoxalines (flavazoles) by acylation, alkylation, halogenation, and aminomethylation of the parent compound is reported and their structure is investigated by ¹H, ¹³C, and ¹⁵N NMR spectroscopy. The restricted rotation about the partial C, N double bond of the N-acyl derivatives 7-10 is studied by dynamic NMR spectroscopy and the barriers to rotation are determined. In order to assign unequivocally the ¹⁵N chemical shifts of N-4 and N-9, in case of 3-substituted flavazoles, exemplary the ¹H, ¹³C, and ¹⁵N NMR chemical shifts of 34, 35, and 39 are also theoretically calculated by quantum chemical methods [ab initio at different levels of theory (HF/6-31G* and B3LYP/6-31G*)].     

Calculations and assignments of endohedral helium-3 chemical shifts of open-cage fullerenes and higher fullerenes

The endohedral ³He NMR chemical shifts of open-cage fullerene compounds and higher fullerenes ³He@C _n (n = 82, 84, 86) have been calculated at the GIAO-B3LYP/3-21G//AM1 level. The predicted ³He NMR chemical shifts of open-cage fullerene compounds agree well with the experimental data. More importantly, the challenging peak assignments in the two ³He NMR spectra of higher fullerenes have been successfully achieved by our computed endohedral ³He chemical shifts in combination with experimental results.     

H-Ge bond activation by tungsten carbonyls: An experimental and theoretical study

The activation of the Ge-H bond and the formation of several hydride complexes, characterized by high-field resonances, have been detected during the ¹H NMR spectroscopy monitoring of the photochemical reaction of Et₃GeH and Et₂GeH₂ with W(CO)₆ and the norbornadiene complex [W(CO)₄(η⁴-nbd)]. The activation of the Ge-H bond of triethylgermane in the photochemical reactions of tungsten(0) complexes has been applied in the hydrogermylation of norbornadiene (nbd), which leads to the formation of endo-triethylgermylnorbornene as the major product. The complex [{W(μ-η²-H-GeEt₂)(CO)₄}₂] has been fully characterized by NMR spectroscopy and by a single-crystal X-ray diffraction study. Evidence for the hydride ligand of the W(μ-η²-H-GeEt₂) group has been provided by ¹H NMR spectroscopy (δ = −9.02, ¹J_H-W = 31 Hz) and by DFT calculations. A DFT study of the structural properties and ¹H NMR chemical shifts of several possible intermediate σ and hydride complexes formed during the photochemical reaction of W(CO)₆ and Et₂GeH₂ has been performed.     

Chloroscabrolides, chlorinated norcembranoids from the Indonesian soft coral Sinularia sp.

Chemical analysis of the Indonesian soft coral Sinularia sp. (order Alcyonacea, family Alcyoniidae) afforded two known and three new C-4 norcembranoids, named chloroscabrolides A (3) and B (4) and prescabrolide (5). Chloroscabrolide A is a pentacyclic norcembranoid including an unprecedented THF-type ring to connect C-13 and C-15; furthermore, it is only the second chlorinated cembranoid derivative to be reported in the literature. The relative configuration of chloroscabrolide A has been established on the basis of a comparison between experimental ¹³C NMR data and DFT-calculated ¹³C NMR chemical shifts. All the isolated norcembranoids have been evaluated for iNOS protein inhibition.     

New antiproliferative 14,15-secopregnane glycosides from Solenostemma argel

Eight new 14,15-secopregnane glycosides, namely argelosides C-J, possessing two ketal functions involved in three five-membered rings, have been isolated from the hairy seeds of Solenostemma argel. Their structures have been established by MS and NMR experiments, combined with quantum mechanical calculations of the ¹³C chemical shifts for the interpretation of the experimental data. On the basis of the obtained results, the structures of argelosides A and B have been revised. Additionally, the effect of these compounds on the VEGF-induced in Kaposi's sarcoma cell proliferation was evaluated. Results indicated that all the compounds reduced the cell proliferation in a dose-dependent manner.     

Structural Elucidation of the O-Antigen Polysaccharide from Escherichia coli O181

Shiga-toxin-producing Escherichia coli (STEC) is an important pathogen associated to food-borne infection in humans; strains of E. coli O181, isolated from human cases of diarrhea, have been classified as belonging to this pathotype. Herein, the structure of the O-antigen polysaccharide (PS) from E. coli O181 has been investigated. The sugar analysis showed quinovosamine (QuiN), glucosamine (GlcN), galactosamine (GalN), and glucose (Glc) as major components. Analysis of the high-resolution mass spectrum of the oligosaccharide (OS), obtained by dephosphorylation of the O-deacetylated PS with aqueous 48 % hydrofluoric acid, revealed a pentasaccharide composed of two QuiNAc, one GlcNAc, one GalNAc, and one Glc residue. The ¹H and ¹³C NMR chemical shift assignments of the OS were carried out using 1 D and 2 D NMR experiments, and the OS was sequenced using a combination of tandem mass spectrometry (MS/MS) data and NMR ¹³C NMR glycosylation shifts. The structure of the native PS was determined using NMR spectroscopy, and it consists of branched pentasaccharide repeating units joined by phosphodiester linkages: →4)[α-l-QuipNAc-(1→3)]-α-d-GalpNAc6Ac-(1→6)-α-d-Glcp-(1→P-4)-α-l-QuipNAc-(1→3)-β-d-GlcpNAc-(1→; the O-acetyl groups represent 0.4 equivalents per repeating unit. Both the OS and PSs exhibit rare conformational behavior since two of the five anomeric proton resonances could only be observed at an elevated temperature.     

Anthracene coupled trans-pyridylcinnamide: a new fluororeceptor for selective sensing of dicarboxylates

trans-Pyridylcinnamide has been established as an alternative hydrogen bonding synthon, in place of urea for carboxylate binding. This alternative motif has been used in the design and synthesis of new fluorescent ‘On-Off’ signalling chemical sensor 1, which is found to bind aliphatic dicarboxylates with moderate binding constants. The recognition ability has been established by fluorescence, UV-vis and ¹H NMR spectroscopic methods. The receptor is found to be selective for long chain pimelate.     

Synthesis of new fluorescent building blocks via the microwave-assisted annulation reaction of 1,1,2-trimethyl-1H-benzo[e]indole with acrylic acid and its derivatives

The reaction of 1,1,2-trimethyl-1H-benzo[e]indole with acrylic acid and its derivatives was employed for the preparation of novel fluorescent building blocks. Treatment of 1,1,2-trimethyl-1H-benzo[e]indole with acrylic acid, acrylamide or tert-butyl acrylate in an autoclave or a microwave reactor at 180–200 °C afforded benzo[e]pyrido[1,2-a]indole derivatives. Various chemical transformations of the latter compounds have been performed to yield functionalized benzo[e]indole scaffolds. The structure assignments were based on data from ¹H and ¹³C NMR spectroscopy and single crystal X-ray analyses. The optical properties of the obtained benzo[e]indoline derivatives were studied by UV–vis and fluorescence spectroscopy.     

Tetratriacontanonaenoic acid, first natural acid with nine double bonds isolated from a crustacean Bathynella natans

The very-long-chain polyunsaturated fatty acid—allZ-4,7,10,13,16,19,22,25,28-tetratriacontanonaenoic acid was determined and identified in the freshwater crustacean species Bathynella natans living in caves of central Europe by means of liquid chromatography—mass spectrometry with atmospheric pressure chemical ionization. The full structure was elucidated by using extensive spectroscopic analysis (¹H and ¹³C NMR, MS, IR and UV) including a chemical method. This acid was described in nature for the first time. A hypothesis is suggested for its origin and biosynthesis.     

Carexanes from Carex distachya Desf.: revised stereochemistry and characterization of four novel polyhydroxylated prenylstilbenes

Carexanes are unusual secondary metabolites isolated from the herbaceous plant Carex distachya. Four new carexanes have been isolated and characterized from the methanolic leaf extract of the plant. All of the structures have been elucidated on the basis of spectroscopic data. The stereochemistry of all the carexane metabolites isolated from the plant, as well as their ¹H and ¹³C NMR spectroscopic assignment, has been revised on the basis of X-ray analysis of carexane D, chemical correlations, and NOESY/ROESY experiments. All the data suggested a cis junction between B and C rings.     

Synthesis and antibacterial activity of methylated N-(4-N,N-dimethylaminocinnamyl) chitosan chloride

The methylated chitosan containing different aromatic moieties were synthesized by two steps, the reductive amination and the methylation. The chemical structures of all methylated derivatives, methylated N-(4-N,N-dimethylaminocinnamyl) chitosan chloride (MDMCMCh), methylated N-(4-pyridylmethyl) chitosan chloride (MPyMeCh), and N,N,N-trimethyl chitosan chloride (TMChC) were characterized by ATR-FTIR and ¹H NMR spectroscopy. The molecular weights of the methylated chitosan derivatives were determined by gel permeation chromatography. The results revealed that the molecular weights of chitosan and N-aryl chitosan derivatives could be reduced by the methylation process. The degree of N-substitution (DS) and the degree of quaternization (DQ) were calculated by ¹H NMR ranged from 50% to 76%, and 28% to 82%, respectively. The water solubility of the methylated chitosan derivatives decreased with increasing concentration and pH. The antibacterial studies of these methylated chitosan derivatives were carried out by using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods against Escherichia coli ATCC 25922 (Gram-negative) and Staphylococcus aureus ATCC 6538 (Gram-positive) bacteria. It was found that the MDMCMCh showed higher antibacterial activity than TMChC while MPyMeCh exhibited reduced antibacterial activity against both bacteria at the same DQ level. In comparison to each of the chemical structure, it was found that the antibacterial activity was not only dependent on the DQ but it was also dependent on the positively charged location and the molecular weight.     

Visualization and quantification of anisotropic effects on the H NMR spectra of 1,3-oxazino[4,3-a]isoquinolines—indirect estimates of steric compression

The anisotropic effects of the phenyl, α- and β-naphthyl moieties in four series of 1,3-oxazino[4,3-a]isoquinolines on the ¹H chemical shifts of the isoquinoline protons were calculated by employing the Nucleus Independent Chemical Shift (NICS) concept and visualized as anisotropic cones by a through-space NMR shielding grid. The signs and extents of these spatial effects on the ¹H chemical shifts of the isoquinoline protons were compared with the experimental ¹H NMR spectra. The differences between the experimental δ (¹H)/ppm values and the calculated anisotropic effects of the aromatic moieties are discussed in terms of the steric compression that occurs in the compounds studied.     

Copper(II) complexes containing chiral substituted 2-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridine ligands: Synthesis, X-ray structural studies and asymmetric catalysis

New chiral N,N-bidentate ligands derived from substituted 2-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridines have been prepared and characterised by means of ¹H, ¹³C NMR spectroscopy and optical rotation. Their Cu(II) complexes were characterized by means of elemental analysis, ¹H NMR spectroscopy and MS. By means of X-ray diffraction, molecular geometry of the complex of 2-(1-methyl-4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridine with copper(II) chloride was determined. The complex exhibits heterochiral dimeric arrangement of two square pyramids with one terminal and one bridge-forming chlorine atoms and two nitrogen atoms in the bases of the pyramids. The tops of these pyramids are formed by the remaining chlorine atoms. The complexes prepared catalyse the Henry reaction with the overall yields of 41-97% and with the maximum enantioselective excess of 19%.     

Determination of pKa values of tenoxicam from H NMR chemical shifts and of oxicams from electrophoretic mobilities (CZE) with the aid of programs SQUAD and HYPNMR

In this work it is explained, by the first time, the application of programs SQUAD and HYPNMR to refine equilibrium constant values through the fit of electrophoretic mobilities determined by capillary zone electrophoresis experiments, due to the mathematical isomorphism of UV-vis absorptivity coefficients, NMR chemical shifts and electrophoretic mobilities as a function of pH. Then, the pK_a values of tenoxicam in H₂O/DMSO 1:4 (v/v) have been obtained from ¹H NMR chemical shifts, as well as of oxicams in aqueous solution from electrophoretic mobilities determined by CZE, at 25 °C. These values are in very good agreement with those reported by spectrophotometric and potentiometric measurements.     

Crystalline O,O′-di-sec-butyl and O,O′-diethyl dithiophosphate platinum(II) complexes: Synthesis, C and P CP/MAS NMR, single crystal X-ray diffraction studies and thermal behaviour

Crystalline bis(O,O′-di-sec-butyldithiophosphato)platinum(II) was prepared and studied by means of ¹³C, ³¹P CP/MAS NMR spectroscopy and single-crystal X-ray diffraction. The unit cell of the platinum(II) compound is comprised of one centrosymmetric mononuclear molecule [Pt{S₂P(O-sec-C₄H₉)₂}₂], in which the dithiophosphate groups display structural equivalence in both ³¹P NMR and XRD data. A pair of the dithiophosphate ligands exhibit the same S,S′-bidentate chelating structural function and form two planar four-membered chelate rings, [PtS₂P], in this molecule. The planar configuration of the [PtS₄] chromophore in structure 1 is governed by the dsp²-hybrid state of platinum(II). The structural states of the dithiophosphate groups in two different samples of complex 1 (one crystallised from ethanol and the other one precipitated from an aqueous solution) are all characterised by almost rhombic ³¹P chemical shift tensors. The observed essential dispersion of the ³¹P NMR chemical shift is caused by a coexistence of six optical isomers of molecule 1. The thermal behaviour of this compound was studied by means of simultaneous thermal analysis (a combination of TG and DSC) under an argon atmosphere. The thermal behaviour shows that the mass of 1 is lost in three steps, involving successive thermal decompositions of the organic and inorganic parts of this compound with platinum(II) dithio-meta-phosphate and reduced metallic platinum as the intermediate and the final products, respectively.     

Isolation and purification of Pseudostellarin B (cyclic peptide) from Pseudostellaria heterophylla (Miq.) Pax by high-speed counter-current chromatography

Pseudostellarin B (cyclic peptide) was isolated and purified from the herbs of Pseudostellaria heterophylla (Miq.) Pax for the first time by high-speed counter-current chromatography (HSCCC) using a two-phase solvent system consisting of n-butanol-ethyl acetate-water (0.6:4.4:5, v/v). The technique can isolate mg levels of the target compound per run with purity better than 96%. The chemical structure of the compound has been positively confirmed by electrospray ionization time of flight (TOF) MS, ¹HNMR, ¹³CNMR and ¹H-¹³CCOSY analyses.     

13C Pulse fourier transform NMR of menthol stereoisomers and related compounds

¹³C NMR spectra of menthol stereoisomers have been determined. The correlations of chemical shifts of these ring carbons with those of stereoisomeric 2-isopropylcyclohexanols are examined. Observed chemical shifts of 1-Me carbons are compared with those predicted from the chemical shifts of stereoisomeric 1-methyl-4-t-butylcyclohexanes. ¹³C NMR spectra of menthyl acetates, and cis and trans p -menthanes have also been examined.