Search Results (10)

Despite the fact that the self-disproportionation of enantiomers (SDE) has been found for several decades and has been widely used in crystallization, sublimation and chromatography for the purification or separation of nonracemic compounds, the phenomenon of SDE in capillary electrophoresis (CE) has never been reported up to now. Here, a new approach to separate enantiomers in CE based on SDE was demonstrated by introducing copper (II) ions into the separation media. The enantiomers of atenolol interact with copper ions to produce positively charged complexes with different electrophoretic mobilities from the single molecules. The dynamic equilibrium between homo- or heterochiral complexes (associates) and single molecules of atenolol enantiomers supports the manifestation of SDE. Different mobilities of the single molecules and associates, and different distribution of two enantiomers between the single molecules and associates caused by their different concentrations, produce a net difference in electrodriven migration velocities of the two enantiomers. The relative movement of two enantiomers causes a zone depleted in one enantiomer at the rear end of sample segment, giving a trapezoidal CE curve with a step at the end. Quantification of enantiomers is achieved according to the step height. The analysis does not rely on the use of enantiomerically pure chiral selector and the result agrees with that obtained by conventional chiral CE using a chiral selector. Full article

α-Pinene is an intriguing monoterpene as it has been reported to undergo the self-disproportionation of enantiomers (SDE) phenomenon via gas chromatography (GC), the only compound to decisively demonstrate this. Examples of the SDE involving the gaseous phase—sublimation aside—are extremely rare. Attempts to replicate the GC results were unsuccessful, though the authors argued convincingly for the difficulty of observing the phenomenon. However, we could effect for α-pinene SDE via evaporation off silica gel and by foam fractionation—albeit the SDE magnitude for both was only very slight—to confirm that α-pinene can undergo the SDE for processes involving a gaseous phase and thus validate the plausibility of the GC report. The indications are that the molecular associations responsible for the various SDE observations of α-pinene occur not in the gaseous phase or the bulk phase but rather in two-dimensional (2D) adsorbed monolayers and are not based on conventional functional group-based intermolecular interactions and instead are, most likely, as a result of homo- and heterochiral packing differences in the 2D monolayers—a well-known 2D chiral-based association packing effect. These are also the first reports of the occurrence of the SDE using an adsorptive bubble separation process (foam fractionation) and involving a gaseous phase other than sublimation, GC, and distillation. Full article

The enzymatic kinetic resolution (EKR) of racemic alcohols or esters is a broadly recognized methodology for the preparation of these compounds in optically active form. Although EKR approaches have been developed for the enantioselective transesterification of a vast number of secondary alcohols or hydrolysis of their respective esters, to date, there is no report of bio- or chemo-catalytic asymmetric synthesis of non-racemic alcohols possessing 1,2,3,4-tetrahydroquinoline moiety, which are valuable building blocks for the pharmaceutical industry. In this work, the kinetic resolution of a set of racemic 1,2,3,4-tetrahydroquinoline-propan-2-ols was successfully carried out in neat organic solvents (in the case of CAL-B and BCL) or in water (in the case of MsAcT single variants) using immobilized lipases from Candida antarctica type B (CAL-B) and Burkholderia cepacia (BCL) or engineered acyltransferase variants from Mycobacterium smegmatis (MsAcT) as the biocatalysts and vinyl acetate as irreversible acyl donor, yielding enantiomerically enriched (S)-alcohols and the corresponding (R)-acetates with E-values up to 328 and excellent optical purities (>99% ee). In general, higher ee-values were observed in the reactions catalyzed by lipases; however, the rates of the reactions were significantly better in the case of MsAcT-catalyzed enantioselective transesterifications. Interestingly, we have experimentally proved that enantiomerically enriched 1-(7-nitro-3,4-dihydroquinolin-1(2H)-yl)propan-2-ol undergoes spontaneous amplification of optical purity under achiral chromatographic conditions. Full article

The purpose of this review is to highlight the necessity of conducting tests to gauge the magnitude of the self-disproportionation of enantiomers (SDE) phenomenon to ensure the veracity of reported enantiomeric excess (ee) values for scalemic samples obtained from enantioselective reactions, natural products isolation, etc. The SDE always occurs to some degree whenever any scalemic sample is subjected to physicochemical processes concomitant with the fractionation of the sample, thus leading to erroneous reporting of the true ee of the sample if due care is not taken to either preclude the effects of the SDE by measurement of the ee prior to the application of physicochemical processes, suppressing the SDE, or evaluating all obtained fractions of the sample. Or even avoiding fractionation altogether if possible. There is a clear necessity to conduct tests to assess the magnitude of the SDE for the processes applied to samples and the updated and improved recommendations described herein cover chromatography and processes involving gas-phase transformations such as evaporation or sublimation. Full article

Knowing the eutectic composition of the binary melting point phase diagrams of the diastereomeric salts formed during the given resolution, the achievable F (F = ee_Dia*Y) value can be calculated. The same value can also be calculated and predicted by knowing the eutectic compositions of the binary melting point phase diagrams of enantiomeric mixtures of the racemic compound or the resolving agent. An explanation was sought as to why and how the crystalline precipitated diastereomeric salt—formed in the solution between a racemic compound and the corresponding resolving agent—may be formed. According to our idea, the self-disproportionation of enantiomers (SDE) has a decisive role when the enantiomers form two nonequal ratios of conformers in solution. The self-organized enantiomers form supramolecular associations having M and P helicity, and double helices are formed. Between these double spirals, with the formation of new double spirals, a dynamic equilibrium is achieved and the salt crystallizes. During this process between acids and bases, chelate structures may also be formed. Acids appear to have a crucial impact on these structures. It is assumed that the behavior of each chiral molecule is determined by its own code. This code validates the combined effect of constituent atoms, bonds, spatial structure, charge distribution, flexibility and complementarity. Full article

2-(2-Fluoro-4-biphenyl) propionic acid (flurbiprofen), from the phenylalkanoic acid family of nonsteroidal anti-inflammatory drugs (NSAID’s), is currently on the pharmaceutical market as a racemate. This racemic compound was tested for its propensity to undergo the self-disproportionation of enantiomers (SDE) phenomenon by various forms of chromatography (SDEvC), such as routine gravity-driven column chromatography, medium-pressure liquid chromatography (MPLC), preparative thin-layer chromatography (PTLC), and size-exclusion chromatography (SEC), as well as by sublimation (SDEvS). Furthermore, examination by nuclear magnetic resonance (NMR) in various solvents found that flurbiprofen exhibited the phenomenon of self-induced diastereomeric anisochronism (SIDA). By measurement of the diffusion coefficient (D), the longitudinal relaxation time (T₁), and the transverse relaxation time (T₂) using NMR, as well as by electrospray ionization-mass spectrometry (ESI-MS) examinations, the preferred intermolecular association was found to be solvent dependent, e.g., heterochiral association was preferred in toluene, while homochiral association was preferred in more polar solvents. This study also attempted, unsuccessfully, to correlate the NMR measurements of flurbiprofen with chromatographic outcomes for the rationalization and prediction of chromatographic results based on NMR measurements. Because the intermolecular hydrogen bonding of the acid groups in flurbiprofen overwhelmingly predominates over other intermolecular interactions, flurbiprofen seemed to represent a good test case for this idea. The behavior of scalemic samples of flurbiprofen is important, as, although it is currently dispensed as a racemate, clinical applications of the R enantiomer have been investigated. SDEvC and SDEvS both have ramifications for the preparation, handling, and storage of enantioenriched flurbiprofen, and this concern applies to other chiral drugs as well. Full article

This perspective is focused on the main parameters determining the results of crystallization of enantiomers or enantiomeric mixtures. It was shown that the ratio of supramolecular and helical associations depends on the eutectic composition of the corresponding enantiomeric mixture. The M and P ratios together with the self-disproportionation (SDE) of enantiomers define the reaction of the racemic compound with the resolving agent. Eventually, each chiral molecule reacts with at least two conformers with different degrees of M and P helicity. The combined effect of the configuration, charge distribution, constituent atoms, bonds, flexibility, and asymmetry of the molecules influencing their behavior was also summarized. Full article

The NMR phenomenon of self-induced diastereomeric anisochronism (SIDA) was observed with an alcohol and an ester. The alcohol exhibited large concentration-dependent chemical shifts (δ’s), which initially led us to erroneously consider whether two enantiomers were in fact atropisomers. This highlights a potential complication for the analysis of chiral compounds due to SIDA, namely the misidentification of enantiomers. A heterochiral association preference for the alcohol in CDCl₃ was determined by the intermolecular nuclear Overhauser effect (NOE) and diffusion measurements, the same preference as found in the solid state. The ester revealed more subtle effects, but concentration-dependent δ’s, observation of intermolecular NOE’s, as well as distinct signals for the two enantiomers in a scalemic sample all indicated the formation of associates. Intermolecular NOE and diffusion measurements indicated that homochiral association is slightly preferred over heterochiral association in CDCl₃, thus masking association for enantiopure and racemic samples of equal concentration. As observed with the alcohol, heterochiral association was preferred for the ester in the solid state. The potential problems that SIDA can cause are highlighted and constitute a warning: Due care should be taken with respect to conditions, particularly the concentration, when measuring NMR spectra of chiral compounds. Scalemic samples of both the alcohol and the ester were found to exhibit the self-disproportionation of enantiomers (SDE) phenomenon by preparative TLC, the first report of SDE by preparative TLC. Full article

α-Aminophosphonic acids are phosphorus analogues of α-amino acids. Compounds of this type find numerous applications in medicine and crop protection due to their unique biological activities. A crucial factor in these activities is the configuration of the stereoisomers. Only a few methods of stereoselective transformation of α-amino acids into their phosphorus analogues are known so far and all of them are based on asymmetric induction, thus involving the use of a chiral substrate. In contrast, we have focused our efforts on the development of an effective method for this type of transformation using a racemic mixture of starting N-protected α-amino acids and a chiral catalyst. Herein, a simple and efficient stereoselective organocatalytic α-amidoalkylation of dimethyl phosphite by 1-(N-acylamino)alkyltriphenylphosphonium salts to enantiomerically enriched α-aminophosphonates is reported. Using 5 mol% of chiral quinine- or hydroquinine-derived quaternary ammonium salts provides final products in very good yields up to 98% and with up to 92% ee. The starting phosphonium salts were easily obtained from α-amino acid derivatives by decarboxylative methoxylation and subsequent substitution with triphenylphosphonium tetrafluoroborate. The appropriate self-disproportionation of enantiomers (SDE) test for selected α-aminophosphonate derivatives via achiral flash chromatography was performed to confirm the reliability of the enantioselectivity results that were obtained. Full article

This work explores the behavior of chiral compound mixtures enriched in one of the enantiomers whilst a typical chromatography on the achiral stationary phase is employed. The influence of several factors, such as the eluent composition, ratio of the compound to the stationary phase, and the initial enatiomeric purity of the compound used on the distribution of the enantiomers in the collected chromatographic fraction, was studied. The obtained results indicate that the phenomenon of Self Disproportionation of Enantiomer (SDE) occurred in all cases, and some of the collected fractions got higher optical purities than the initial one. Thus, achiral column chromatography could be applied in some cases as the simplest approach for chiral purification. Based on the experimental results and DFT calculations, an alternative concept explaining the SDE phenomenon was proposed. Due to its generality and simplicity, SDE may also be responsible for the formation of the first chiral non-racemic compounds on the early Earth. Full article