Chiral Lanthanide Shift Reagents Research Articles

Praseodymium Metallacrown-Based NMR Probe for Enantioselective Discrimination of Mandelate Anions in Water.

Recently, the enhanced interest in water-soluble aminohydroximate Ln(III)-Cu(II) metallacrowns (MC) is largely due to their fascinating structural chemistry, diverse properties and ease of synthesis. We examined the water-soluble praseodymium(III) alaninehydroximate complex Pr(H2O)4[15-MCCu(II)Alaha-5]·3Cl (1) as a highly effective chiral lanthanide shift reagent for NMR analysis of the biologically relevant (R/S)-mandelate (MA) anions in aqueous media. The R-MA and S-MA enantiomers can be easily discriminated in the presence of small (1.2-6.2 mol %) amounts of MC 1 by the 1H NMR signals of multiple protons exhibiting an enantiomeric shift difference (ΔΔδ) of 0.06 ppm up to 0.31 ppm. Additionally, a possibility of coordination of MA to the metallacrown was investigated by the ESI-MS technique and a Density Functional Theory modeling of the molecular electrostatic potential and noncovalent interactions.

Exchange-modified DOSY experiments. the use of chiral solvating agents and lanthanide shift reagents as matrices

(S)-BINOL and Eu(fod)3 were tried as matrices to improve DOSY performance and Dt and MW prediction power on small organic molecules.

Two goitrogenic 1,3-oxazolidine-2-thione derivatives from Brassicales taxa: Challenging identification, occurrence and immunomodulatory effects

1,3-Oxazolidine-2-thione derivatives are glucosinolate-related food constituents known to impart (thyreo)toxic properties to some cruciferous vegetables. In this work, 5,5-dimethyl-1,3-oxazolidine-2-thione and (-)-(R)-5-phenyl-1,3-oxazolidine-2-thione, known goitrogens, were isolated from Draba lasiocarpa Rochel (Brassicaceae) and Reseda luteola L. (Resedaceae), respectively, and were fully spectrally characterized. Subsequently, the occurrence of the two 1,3-oxazolidine-2-thiones was verified in six additional taxa out of in total 78 screened Serbian Brassicales taxa. The stereochemistry of 5-phenyl-1,3-oxazolidine-2-thione was inferred from nuclear magnetic resonance experiments with a chiral lanthanide-shift reagent, employed in this work for the first time for this type of compounds. Unexpectedly, during gas chromatography, 5-phenyl-1,3-oxazolidine-2-thione underwent an unreported thermal core isomerization (1,3-oxazolidine-2-thione to 1,3-thiazolidine-2-one). These goitrogenic volatile glucosinolate products were tested for their effect on rat macrophage viability (three assays) and nitric oxide production. It was shown that the compounds displayed different levels of cytotoxicity. All tested compounds caused a significant lactate dehydrogenase leakage, but only (R)-5-phenyl-1,3-oxazolidine-2-thione statistically significantly reduced macrophage mitochondrial activity, whereas the racemic 5-phenyl-1,3-oxazolidine-2-thione and 5,5-dimethyl-1,3-oxazolidine-2-thione had little or no effect. Again only (R)-5-phenyl-1,3-oxazolidine-2-thione exerted nitric oxide production-inhibiting properties, suggesting the higher immunomodulatory potential of this enantiomer compared with its antipode and racemic mixture.

Precise Determination of Enantiomeric Excess by a Sensitivity Enhanced Two-Dimensional Band-Selective Pure-Shift NMR.

Unambiguous identification and precise quantification of enantiomers in chiral mixtures is crucial for enantiomer specific synthesis as well as chemical analysis. The task is often challenging for mixtures with high enantiomeric excess and for complex molecules with strong (1)H-(1)H scalar (J) coupling network. The recent advancements in (1)H-(1)H decoupling strategies to suppress the J-interactions offered new possibilities for NMR based unambiguous discrimination and quantification enantiomers. Herein, we discuss a high resolution two-dimensional pure-shift zCOSY NMR method with homonuclear band-selective decoupling in both the F1 and F2 dimensions (F1F2-HOBS-zCOSY). This advanced method shows a sharp improvement in resolution over the other COSY methods and also eliminates the problems associated with the overlapping decoupling sidebands. The efficacy of this method has been exploited for precise quantification of enantiomeric excess (ee) ratio (R/S) up to 99:1 in the presence of very low concentrations of chiral lanthanide shift reagents (CLSR) or chiral solvating agents (CSA). The F1F2-HOBS-zCOSY is simple and can be easily implemented on any modern NMR spectrometers, as a routine analytical tool.

Selective excitation and detection of maximum quantum coherence of a group of scalar coupled protons in chiral molecules: an NMR experiment for enantiodiscrimination

The 1H NMR spectroscopic discrimination of enantiomers in the solution state and the measurement of enantiomeric composition is most often hindered due to either very small chemical shift differences between the discriminated peaks or severe overlap of transitions from other chemically non-equivalent protons. In addition the use of chiral auxiliaries such as, crown ether and chiral lanthanide shift reagent may often cause enormous line broadening or give little degree of discrimination beyond the crown ether substrate ratio, hampering the discrimination. In circumventing such problems we are proposing the utilization of the difference in the additive values of all the chemical shifts of a scalar coupled spin system. The excitation and detection of appropriate highest quantum coherence yields the measurable difference in the frequencies between two transitions, one pertaining to each enantiomer in the maximum quantum dimension permitting their discrimination and the F2 cross section at each of these frequencies yields an enantiopure spectrum. The advantage of the utility of the proposed method is demonstrated on several chiral compounds where the conventional one dimensional 1H NMR spectra fail to differentiate the enantiomers.

NMR-based Enantiodifferentiation of Chiral trans-2-Phenylcyclopropane Derivatives Using a Chiral Lanthanide Shift Reagent

NMR-based Enantiodifferentiation of Chiral trans-2-Phenylcyclopropane Derivatives Using a Chiral Lanthanide Shift Reagent

The use of base line technique for the determination of optical purities using NMR and chiral lanthanide shift reagents [proceedings

The use of base line technique for the determination of optical purities using NMR and chiral lanthanide shift reagents [proceedings

Application of selective F1 decoupled 1H NMR for enantiomer resolution and accurate measurement of enantiomeric excess at low chiral substrate/auxiliary concentration

The higher substrate and chiral auxiliary concentration is a pre-requisite to obtain efficient separation of 1H NMR signals of enantiomers. The higher concentration of chiral lanthanide shift reagents provides broadened spectral lines resulting in a severe loss of resolution between the enantiomer resonances. In order to circumvent such difficulties, herein we present the application and the usefulness of a selective F1 decoupled correlation (COSY) experiment which yields proton decoupled proton spectra in the indirect dimension. The potentiality of the experiment is demonstrated on several chiral compounds possessing different functional groups, employing either a lanthanide shift reagent or a solvating reagent as chiral auxiliaries.

ChemInform Abstract: Europium (S,S)-Ethylenediamine-N,N′-disuccinate as a Chiral Lanthanide Shift Reagent for Aqueous Solutions.

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ChemInform Abstract: Transformations of Unsaturated Acyclic Sugars into Enantiomerically Pure Norbornene Derivatives.

Abstract The C 7 acyclic unsaturated-sugar ester 1 , derived from l -arabinose, and its enantiomer serve as convenient dieneophiles for chirality transfer for synthesis of optically pure carbocyclic derivatives through cycloaddition reactions. Reaction of 1 with cyclopentadiene may be controlled to give preparative access to the 5,6-disubstituted norbornene adducts 4a , 5a , and 7a , according to the conditions used. The distribution of the four possible isomeric products from this cycloaddition was quantitated, and the effect of substitutional variation on the precursor dienophile 1 was also examined. Adducts 4a and 5a were transformed into such substituted carbocycles of known absolute configuration as the methyl esters ( 11 and 12 ) of norbornene (bicyclo[2.2.1]hept-2-ene)-6-carboxylic acid and nortricyclane (tricyclo[2.2.1.0 2,6 ]heptane)-3-carboxylic acid in optically pure form, specifically through decarbonylation reactions using RhCl(PPh 3 ) 3 (Wilkinson's complex) and [Rh(dppp) 2 ]Cl[dppp = Ph 2 P(CH 2 ) 3 PPh 2 ]. The optical purity of 12 was established by the use of a chiral lanthanide shift-reagent.

Enantiomeric Differentiation of Oxygenated Bicyclo[2.2.1]heptane Derivatives by 13C NMR Spectroscopy Using Yb(hfc)3

ABSTRACT The 13C NMR behavior of 10 oxygenated compounds (ketones, alcohols, acetates) bearing the bicyclo[2.2.1]heptane skeleton was examined in the presence of a chiral lanthanide shift reagent (Yb(hfc)3). For each compound, we measured the lanthanide-induced shift (LIS) on the signals of the carbons and the splitting of signals, enabling the enantiomeric differentiation. The enantiomeric splitting was observed for the majority of signals in the spectrum of each compound.

Determination of the absolute configuration of the glucosinolate methyl sulfoxide group reveals a stereospecific biosynthesis of the side chain

Glucosinolates are plant metabolites containing an anionic nitrogeneous thioglucosidic core structure and a structurally diverse amino acid-derived side chain, which after hydrolysis by thioglucohydrolases (myrosinases) afford biological active degradation products such as nitriles and isothiocyanates. Structural diversity in glucosinolates is partially due to enzymatic modifications occurring on the preformed core structure, like the recently described oxidation of sulfides to sulfoxides catalyzed by a flavin monooxygenase identified in Arabidopsis thaliana. The enzyme product, 4-methylsulfinylbutylglucosinolate, bears a chiral sulfoxide group in its side chain. We have analyzed the epimeric purity of 4-methylsulfinylbutylglucosinolate by NMR methods using a chiral lanthanide shift reagent. The absolute configuration of the sulfoxide group has been established by comparing the 1H NMR spectra of the two sulfoximine diastereomers of natural 4-methylsulfinylbutylglucosinolate. According to our data, 4-methylsulfinylbutylglucosinolate isolated from broccoli and A. thaliana is a pure epimer and its sulfoxide group has the R S configuration. The product of the A. thaliana flavin monooxygenase has these same properties demonstrating that the enzyme is stereospecific and supporting its involvement in glucosinolate side chain formation.

Enantiomeric differentiation of oxygenated p‐menthane derivatives by 13C NMR using Yb(hfc)3

The (13)C NMR behaviour of 21 p-menthanic terpene bearing an oxygenated function (alcohol, ketone, acetate) was examined in the presence of a chiral lanthanide shift reagent (Yb(hfc)(3)). For each monocyclic compound, we measured the lanthanide-induced shift (LIS) on the signals of the carbons and the splitting of signals allowing the enantiomeric differentiation. Some general features were found about their LIS behaviour: experimental data establishing distinct patterns for carvomenthone-like compounds and menthone-like compounds. The enantiomeric splitting was observed for the majority of signals in the spectrum of each compound. In the case of alcohols and acetates, the influence of the relative stereochemistry (cis vs trans) of isopropyl(ene) and the binding function was discussed.

Chiral recognition of ethers by NMR spectroscopy

Enantiomers of chiral ethers and acetals are notoriously difficult to differentiate because their reactivity is low and they are poor donors to any Lewis acid or metal ion. As an exception, epoxides are somewhat better donors. This review describes the properties of ethers, explains NMR methods for their chiral recognition and describes successful examples of ether differentiation. The majority of literature reports deals with chiral lanthanide shift reagents and dirhodium tetracarboxylate complexes, which were used as enantiopure auxiliaries to create diastereomeric adducts with dispersed (1)H and (13)C NMR signals. The various methods are compared as to which is best suited for which purpose.

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)

Enantiomeric purity determination of acetyl- l-carnitine by NMR with chiral lanthanide shift reagents

Enantiomer signal separation of acetyl-carnitine chloride was obtained on a 500 MHz Nuclear Magnetic Resonance ( 1H NMR) analysis by fast diastereomeric interaction with chiral shift reagents such as chiral lanthanide-camphorato or chiral samarium-pdta shift reagents. Effects of the kinds of chiral shift reagents and the molar ratio of chiral shift reagent to acetyl-carnitine chloride on enantiomer signal separation were investigated and evaluated. Optimization of the experimental conditions provided two significant split signals for the enantiomers, leading to the successful quantitative analysis. Distinguishment of 0.5% of the minor enantiomer ( d-form) in acetyl- l-carnitine chloride was found to be possible by 1H NMR with tris[3-(heptafluoropropylhydroxymethylene)- d-camphorato] and praseodymium derivative, (Pr[hfc] 3), as chiral shift reagents.

Enantiomeric differentiation of acyclic terpenes by13C NMR spectroscopy using a chiral lanthanide shift reagent

The 13C NMR behaviour of ten acyclic terpene alcohols was examined in the presence of a chiral lanthanide shift reagent (CLSR). For each alcohol, we measured the lanthanide-induced shift (LIS) on the signals of the carbons and the splitting of some signals, which allowed the enantiomeric differentiation. As expected, the LIS decreased with the number of bonds between the binding function and the considered carbon. The enantiomeric splitting is observed for several signals in the spectrum of each compound. The influence of the hindrance of the binding function (primary, secondary or tertiary alcohol) and that of the stereochemistry of the double bonds is discussed.

Validation of Lanthanide Chiral Shift Reagents for Determination of Absolute Configuration: Total Synthesis of Glisoprenin A

[structure: see text] The complete stereostructure of the natural product (+)-glisoprenin A had been predicted via a novel application of chiral lanthanide shift reagents. Confirmation of the predicted stereostructure of (+)-glisoprenin A and validation of the chiral lanthanide shift approach have now been achieved through total synthesis.

Application of Chiral Lanthanide Shift Reagents for Assignment of Absolute Configuration of Alcohols

[structure: see text] The absolute configuration of secondary and tertiary alcohols can be predicted from analysis of the chemical shift behaviors of the CX- and CY-carbons in the presence of (R)- and (S)-Pr(tfc)3 as formulated in the boxes.

Observing the enantiomeric 1H chemical shift non-equivalence of several α-amino ester signals using tris[3-(trifluoromethylhydroxymethylene)-(+)-camphorato]samarium(III): a chiral lanthanide shift reagent that causes minimal line broadening

The chiral lanthanide shift reagent, tris[3-(trifluoromethylhydroxymethylene)-(+)-camphorato]samarium(III) [Sm(tfc) 3], was shown to resolve the 1H NMR signals of the enantiomers of α-amino esters without causing serious line broadening. This distinctive feature of Sm(tfc) 3 made it possible to examine the enantiomeric chemical shift non-equivalence of several protons in ester substrates, increasing the reliability of the empirical assignment of the absolute configuration as compared to earlier techniques.