Shift Reagent Research Articles

A new flavone from antioxidant extracts of Pistacia terebinthus

Acetone and methanol extracts of the fruits of Pistacia terebinthus L. subsp. terebinthus L. were studied for their antioxidant activity by investigating their total phenolic and flavonoid contents, β-carotene bleaching potential, DPPH radical scavenging effect, scavenging activity on superoxide anion radical, reducing power, and metal chelating effect on ferrous ion. Both extracts showed very similar chemical profile by checking on TLC plates, and exhibited high scavenging activity on superoxide anion radical and DPPH radical. Due to these similarities they were combined and fractionated on a silica gel column for their constituents, and the most active three fractions in DPPH assay were purified to afford a new flavone 6′-hydroxyhypolaetin 3′-methyl ether ( 1) besides a group of known flavonoids apigenin, luteolin, luteolin 7- O-glucoside, quercetin, quercetagetin 3-methyl ether 7- O-glucoside, isoscutellarein 8- O-glucoside. Their structures were established by UV, UV shift reagents, and 1H NMR spectroscopic techniques. Antioxidant activity of the new flavone was investigated by β-carotene bleaching and DPPH radical scavenging activity methods, and it showed a high activity in the first system, but not so good in the latter.

Easily Accessible Chiral Imidazolinium Salts Bearing Two Hydroxy‐Containing Substituents as Shift Reagents and Carbene Precursors

AbstractThe behavior of new enantiopure imidazolinium salts bearing two hydroxy‐containing substituents as chiral shift reagents and as carbene precursors for diethylzinc addition to aldehydes is presented. The new hydroxy‐containing imidazolinium salts can be prepared in a few steps from amino alcohols and qualify as new tridentate ligands and ionic liquids.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Proton NMR assignments for R,S‐1,1′‐binaphthol (BN) and R,S‐1,1′‐binaphthyl‐2,2′‐diyl hydrogen phosphate (BNDHP) interacting with bile salt micelles

We report proton chemical shifts for two model chiral analytes that are commonly used in the study of micellar electrokinetic capillary chromatography (MEKC), R,S-1,1'-binaphthol (1, BN) and R,S-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (2, BNDHP), in the absence and presence of monomers and micelles of sodium cholate and sodium deoxycholate. The analytes undergo fast exchange in and out of the micelles, which perturbs the analytes' chemical shifts, and which we use to resolve some resonances that are degenerate at both 300 and 600 MHz. Although BN and BNDHP are simple molecules, the proton assignments are only unambiguously established with the aid of the exchange with micelles, an attractive alternative to other methodologies such as the use of paramagnetic shift reagents which may also cause spectral distortions. We rely also upon 2D-NOE spectra of samples in the presence of micelles to perform these assignments. Recently published assignments, which were based upon 2D-COSY spectroscopy, appear to be in error and are corrected here. Finally, we note that these shifts are information-rich reporters on the nature of the interactions of these model analytes with the micelles.

Identification of flavonols in leaves of Maytenus ilicifolia and M. aquifolium (Celastraceae) by LC/UV/MS analysis

A comparative analysis of the flavonoid components of the leaves of two medicinal plants known in Brazil as “espinheira santa”, namely, Maytenus ilicifolia Mart. ex Reiss. and M. aquifolium Mart. (Celastraceae), and a hybrid plant, M. aquifolium × M. ilicifolia, has been carried out using high-performance liquid chromatography coupled with photodiode array UV detection and mass spectrometry. One methoxyflavonoid glycoside and 18 flavonol-3- O-glycosides were identified in the extracts on the basis of their on-line UV spectra (measured in the absence and presence of shift reagents) and multiple stage mass spectral data. Fingerprint analysis of the flavonoid extracts revealed significant differences in the profiles of the two Maytenus species, while the hybrid plant contained flavonoids found in both parent species.

Synthesis and properties of a diastereopure ionic liquid with planar chirality

An imidazolium-based ionic liquid with cyclophane-type planar chirality was synthesized in an optically pure form for the first time. The resultant ionic liquid existed as a liquid at room temperature ( T g = −35 °C), and was found to be applicable as an NMR chiral shift reagent for racemic anions. Excellent robustness of the ionic liquid to a highly elevated temperature (270 °C) was proved from the viewpoints of isomerization and thermal decomposition.

P-26 アミノ酸およびペプチドの絶対配置決定に有用なキラルランタニドシフト試薬(ポスター発表の部)

P-26 アミノ酸およびペプチドの絶対配置決定に有用なキラルランタニドシフト試薬(ポスター発表の部)

Chiral Imidazolinium Salts: Lewis Acids, Shift Reagents and Ionic Liquids

Using standard methodology for imidazolidine ring synthesis, new chiral mono- and bis-imidazolinium salts have been prepared in good to excellent yields. The final step involves quaternization and counter anion exchange. These salts show good catalytic activity in aza-­Diels-Alder reactions; however, no asymmetric induction was observed. Tested as chiral shift reagents, the bis-imidazolinium salts were able to resolve the 19F and 1H NMR signals belonging to the two enantiomers of the potassium salt of Mosher’s acid.

Chrozophorin: a new acylated flavone glucoside from Chrozophora tinctoria (Euphorbiaceae)

Preparative reversed-phase HPLC analysis of the methanol extract of the aerial parts of Chrozophora tinctoria (Euphorbiaceae) yielded five flavonoid glycosides, quercetin 3-O-rutinoside (1, rutin), acacetin 7-O-rutinoside (2), apigenin 7-O-b-D-[(6-p-coumaroyl)]-glucopyranoside (3), apigenin 7-O- b-D-glucopyranoside (4) and apigenin 7-O-b-D-[6-(3,4-dihydroxybenzoyl)]-glucopyranoside (named, chrozophorin, 5), the last one being a new natural product. The structures of these compounds were elucidated unambiguously by UV spectroscopic analyses using shift reagents, ESIMS, and 1D and 2D NMR spectroscopic techniques. The free-radical scavenging activity of the methanol extract (RC50 = 2.24 x 10-1 mg/mL) as well as the isolated compounds (1-5) (RC50 = 4.38 x 10-3, 2.26 x 10-2, 7.69 x 10-4, 8.71 x 10-3 and 3.19 x 10-4 mg/mL, respectively) were assessed by the DPPH assay.

Exploring crown ethers as shift reagents for ion mobility spectrometry.

A series of crown ethers, 12-crown-4, 15-crown-5, 18-crown-6, and dibenzo-30-crown-10, are examined as a possible means of shifting the mobilities of peptide ions. In this approach, a crown ether is added to a solution containing a mixture of peptides and is electrosprayed into the gas phase in order to create distributions of peptide-crown complexes. The ion complexes have different mobilities than the naked peptide ions, and the crown ether molecules appear to interact specifically with basic sites in the peptides thus providing some sequence selectivity. After the peptide-crown complexes are separated by ion mobility spectrometry, the ions can be collisionally activated to dissociate the complex (forming the naked peptide ions) prior to m/z analysis. The overall effect is that complex formation shifts peptide ions to different regions of the mobility spectrum, extending the ability to resolve components. The approach is illustrated by examining isobaric dipeptides as well as a combinatorial library containing 27 tripeptides. Cross sections for the series of crown ether ions and complexes that are observed are reported.

Versatile and Practical Chiral Shift Reagent with Hydrogen-Bond Donor/Acceptor Sites in a Macrocyclic Cavity

[structure: see text] Bifunctional macrocycle 1 with C2 symmetry was newly synthesized. NMR studies demonstrated that receptor 1 functions as a chiral shift reagent (solvating agent) that is highly effective for a wide range of chiral compounds having a carboxylic acid, oxazolidinone, lactone, alcohol, sulfoxide, sulfoximine, isocyanate, or epoxide functionality. Binding constants were determined to investigate the binding behavior of 1.

Bottom-Up Synthesis of Optically Active Oligonaphthalenes: Three Different Pathways for Controlling Axial Chirality1

The oxidative homocoupling of optically active binaphthalenes 1a-d with a stoichiometric amount of CuCl2 and amines afforded quaternaphthalenes 2a-d in up to 93% de. The high diastereoselectivities were achieved through three different pathways (epimerization of the axis together with diastereoselective crystallization, thermodynamic, and kinetic control pathways). The type of side chains on the naphthalene influenced which pathway dominates. Three pathways were applicable to octinaphthalenes (8a-d) and hexadecanaphthalene 10a with 46-99% de. The absolute configuration of the newly formed axial bond was determined by (1) X-ray crystallographic analysis, (2) transformation to known compounds 15 and 16, (3) CD spectra of oligonaphthalenes with two pyrene rings as exciton parts, and (4) the shift values in 13C NMR spectra of 13C-enriched derivatives 29-31 toward chiral shift reagent Eu(+tfc)3.

On‐line identification of further flavone C‐ and O‐glycosides from sugarcane (Saccharum officinarum L., Gramineae) by HPLC‐UV‐MS

HPLC-UV-MS (APCI-MS/MS and CID/MS) was utilised for the identification of eight additional flavone glycosides from sugarcane (Saccharum officinarum L., Gramineae) extracts of bagasse, leaves and juice ('garapa'). Relevant information about substitution patterns was obtained through UV detection using post-column addition of shift reagents, while tandem MS provided structural information confirming the proposed structures of the C-glycosides vitexin, orientin, luteolin-8-C-(rhamnosylglucoside), 4',5'-dimethyl-luteolin-8-C-glycoside and the isomeric pair schaftoside-isoschaftoside, besides the O-glycosides tricin-7-O-neohesperidoside and tricin-7-O-glycoside.

Helical chirality in hexamethylene triperoxide diamine

The primary explosive hexamethylenetriperoxide diamine has previously been found to exist in the solid state as a racemic mixture of helically chiral, threefold symmetric enantiomers; another enantiomeric pair of low-energy conformers has been predicted, but has never been observed. We show by solution 2D NMR at 14 T, in achiral solution and by addition of chiral shift reagents, that all four optically isomeric conformers coexist at slow equilibrium on the NMR timescale at room temperature, and can be observed. Calculations of the 1H and 13C NMR chemical shifts using gauge-including atomic orbital methods are in excellent agreement with experiment; thermochemical calculation of the free energies in solution are in somewhat worse agreement, but correctly predict the relative stability of the conformers. Analysis of the effects of chiral shift reagents on the NMR spectra suggests that discrimination between chiral isomers is primarily around the molecular equator, around which the enantiomeric gauche O--O linkages are arrayed.

Polarographic chemometric determination of zinc and nickel in aqueous samples

Polarographic chemometric methods were applied to the determination of zinc and nickel in aqueous solutions previously acidified with 0.1 M acetate buffer (pH 4.2). The studied methods are multivariate methods including classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS); derivative ratio methods (first, 1D and second, 2D derivative ratio). A comparative study was considered. The studied chemometric methods do not need the presence of any reduction potential shift reagent in spite of the great overlap between the two metals polarograms. A training set consisting of 10 binary mixture solutions in the possible combinations containing 0.13–9.30 μg/ml Zn(II) and 0.20–12.25 μg/ml Ni(II) was used to develop the chemometric calibrations (CLS, PCR and PLS). A validation set containing the synthetic mixtures in the range of 0.29–9.00 μg/ml for Zn(II) and 0.30–11.60 μg/ml for Ni(II) was used to validate the multivariate calibrations. Same mixtures were used to develop the derivative ratio methods. The polarograms were recorded and their current values were measured within the potential range −920 to −1052 mV at 2 mV intervals. The mean percentage recoveries obtained using CLS, PCR and PLS were found to be 99.5 ± 1.5%, 100.0 ± 1.1% and 100.0 ± 1.0% for Zn(II) and 99.4 ± 1.3%, 99.7 ± 1.2% and 99.9 ± 1.0% for Ni(II), respectively. The mean percentage recoveries obtained using 1D at −950 mV, 1D at −1010 mV, 1D at −950 mV– 1D at −1010 mV and 2D at −986 mV for Zn(II) were found to be 99.7 ± 1.2%, 99.2 ± 1.6%, 99.4 ± 1.4% and 99.4 ± 1.4%; and using 1D at −1030 mV and 2D at −1010 mV for Ni(II) were found to be 100.5 ± 1.3% and 100.4 ± 1.3%, respectively. Interferences due to the presence of Cd, Co, Pb, Fe, Mn, Ca, Mg, Cu and Al were studied. The applicability of the proposed methods was assessed through the determination of both metals in tap drinking-water. Samples were subjected if required up to a 20-fold preconcentration step by microwaving in pyrex vessels. The results were compared with those obtained using the zincon and the heptoxime colorimetric reference methods for the determination of zinc and nickel, respectively.

Chiral shift reagent catalyzed, diastereoselective imino Diels–Alder reaction — Synthesis of pyrazolyltetrahydroquinolines

A new, target oriented, highly diastereoselective synthesis of pyrazolyltetrahydroquinolines was attempted successfully. The chiral shift reagent Eu(tfc) was found to be a better choice for inducing diasteroselectivity.Key words: imino Diels–Alder reaction, chiral shift reagent catalyst, pyrazolyltetrahydroquinolines, diastereoselectivity, antibacterial activity.

The preparation of new enantiopure imidazolinium salts and their evaluation as catalysts and shift reagents

A series of new chiral imidazolinium salts were prepared and tested as catalysts. It was possible to show that bis-imidazolinium salts had a higher reactivity than mono-imidazolinium salts. In addition a chiral discrimination of the bis-imidazolinium salts with the potassium salt of racemic Mosher’s acid was proven by NMR studies.

Determination of absolute configuration of secondary alcohols using new chiral auxiliary and chemical shift calculation

A new chiral carboxylic acid 1 was synthesized for determination of absolute configuration of secondary alcohols. Several chiral alcohols were converted to esters with 1 . Their experimental esterification shift changes were successfully reproduced by the chemical shift simulation method combined with molecular dynamic simulation.

Diastereoisomerism of thiol complexes of arsenic acids and pseudoasymmetry of arsenic: a1H and13C NMR study

Diastereoisomeric complexes of methylphenylarsinic acid and (L)-glutathione could be partially separated by HPLC, but the separated compounds rapidly racemized, presumably by pyramidal inversion at the arsenic atom. Hydrolysis of the diastereoisomeric complexes yielded methylphenylarsinous acid as a pair of enantiomers revealed by a 1H NMR study with an asymmetric lanthanide shift reagent. Methylphenylarsinous acid was also synthesized as an enantiomeric pair, shown by an asymmetric shift reagent experiment, by the hydrolysis of iodomethylphenylarsine. 1H and 13C NMR spectroscopy were used to demonstrate that complexing of phenylarsonic acid with (R,S)-3-mercapto-1,2-propanediol and with (R,S)-1-mercapto-2-propanol yielded, in each case, a pair of enantiomers, PhAs[(R)-ligand)]2, PhAs[(S)-ligand)]2, in which the homomorphic ligands were diastereotopic, and a pair of diastereoisomers, PhAs[(R)-ligand][(S)-ligand], which differed from each other in the configuration about the pseudoasymmetric arsenic atom.

A new chiral lanthanide NMR probe for the determination of the enantiomeric purity of α-hydroxy acids and the absolute configuration of α-amino acids in water

A water-soluble, enantiopure lanthanide complex, SSS-[Ln x L3], has been assessed as an effective chiral derivatizing agent for the determination of the enantiomeric purity of alpha-hydroxy acids in aqueous solution. The complex displays superior chemical shift non-equivalence (DeltaDeltadelta approximately 2-11 ppm) for the diastereomeric resonances of interest compared to lanthanide shift reagents reported in the literature (DeltaDeltadelta <0.1 ppm, typically). 1H NMR studies have also revealed that SSS-[Ln x L3] can be used to determine the absolute configuration of alpha-amino acids at physiological pH, in water. The ability of SSS-[Ln x L3] to signal anion binding and, in particular, to distinguish between diastereomers through optical techniques such as lanthanide luminescence and circular dichroism has also been assessed.

Evaluation of sparteine-like chiral diamines in the enantioselective lithiation–electrophilic trapping of an O-alkyl carbamate

Seven (+)-sparteine-like diamines and (−)-sparteine were evaluated in the diamine-mediated asymmetric lithiation–trapping of an O-alkyl carbamate. The (+)-sparteine-like diamines (≥98 : 2 er by chiral shift NMR spectroscopy) were prepared from (−)-cytisine (>99 : 1 er by chiral HPLC of N-benzyl cytisine) and two new (+)-sparteine-like diamines containing N-CD3 substituents were included as part of this study. The following results from the ligand evaluation study were obtained: (−)-sparteine is unrivalled in its ability to induce near-perfect enantioselectivity (99 : 1 er); N-methyl diamine and the two N-CD3-substituted diamines are the optimal (+)-sparteine surrogates (up to 96 : 4 er); sterically more hindered N-alkyl substituents gave reduced enantioselectivity (N-iso-propyl: 86 : 14 er; N-CH2tBu: 54 : 46 er). From a synthetic point of view, these results show that either enantiomer of α-substituted O-alkyl carbamates can be obtained by enantioselective lithiation–trapping using (−)-sparteine and the N-methyl (+)-sparteine surrogate.