Littérature scientifique sur le sujet « Enantiomeric purification »

Efficient separation of enantiomers is critical in the chemical, pharmaceutical, and food industries. However, conventional separation methods, such as chromatography, crystallization, and enzymatic kinetic resolution, require high energy costs and specific reaction conditions for the efficient purification of one enantiomer. In contrast, membrane-based processes are continuous processes performed with less energy than conventional separation processes. Enantioselective polymer membranes have been developed for the chiral resolution of pharmaceuticals; however, it is difficult to generate sufficient enantiomeric excess (ee) with polymer membranes. In this work, a homochiral filler of L-His-ZIF-8 was synthesized by the ligand substitution method and mixed with polyamide(imide) (i.e., Torlon®) to fabricate an enantioselective mixed-matrix membrane (MMM). The enantio-selective separation of R-1-phenylethanol over S-1-phenylethanol was demonstrated with a 25 wt% loaded L-His-ZIF-8/Torlon® MMM in an organic solvent nanofiltration (OSN) mode.

A simple method for qualitative and quantitative determination of PCB95, 132, 149 and 174 enantiomers in soils and sediments using GC-ECD/MS was proposed. On the promise of good purification efficiency, high recovery and easy operability, H2SO4 washing and a multi-layer column filled with 1 g anhydrous sodium sulfate, 2 g 10% silver nitrate-impregnated silica gel, 4 g 3.3% water-deactivated silica gel and 1.5 g anhydrous sodium sulfate were selected as purification procedures. The chromatographic conditions were optimized to obtain the best enantiomeric separation. Complete baseline separations were achieved for PCB95, 132 and 149, as well as approximate baseline separation was obtained for PCB174. This method was proved to have highly satisfactory accuracy, precision and sensitivity with mean recoveries of target PCB enantiomers in range of 71.42−80.12% and RSD<6%. The detection limits of the method were 11.37−25.36 pg•g−1.

The review is devoted to self-disproportionation of enantiomers (SDE) phenomenon which has been observed for many different classes of chiral organic compounds. The SDE phenomenon occurs when the fractionation of an enantioenriched sample due the application of a physicochemical process under achiral conditions results in the variation of the proportion of the enantiomers present across the fractions, though the overall composition in terms of the sample ee remains unchanged. The SDE process can be considered in terms of separating the excess enantiomer from the racemate. The basic terminology related to SDE was described. The formation of the SDE under chromatographic conditions is the result of an association process occurring in a solution of a chiral, non-racemic compound. Information on preferred interactions leading to homo-/heterochiral supramolecules can be provided by quantum chemical calculations, NMR spectroscopy and comparison of crystal structures of the racemic and enantiomeric crystals. Several examples of the chromatographic experiments with different classes of compounds were given in two purposes 1) to highlight the possibility of application SDE during column chromatography as the method for enantiopurification of the chiral, non-racemic compounds; 2) to demonstrate that a standard workup (chromatographic purification, evaporation) can alter the stereochemical outcome of asymmetric reactions

Resolution process of tofisopam has been re-evaluated now based on our new investigations. Originally, it was carried out in the water-chloroform system, where the intermediate salt of high diastereomeric excess was described as (R)-TOF·(R,R)-DBTA·(H2O)3. Opposed to previous assumptions, we have actually found that a different solvate composition, (R)-TOF‐(R,R)-DBTA-CHCl3, forms with chloroform, in which molecules of CHCl3 are captured and held with different strengths. Moreover, resolution of TOF with (R,R)-DBTA is possible (and favourable) in water-free solvent and solvent mixture. However, presence of chloroform is essential, and thus, chloroform is also a suitable solvent alone. Among the tested solvents, toluene-chloroform mixture results in the highest resolution efficiency, while the highest enantiomeric purity was achieved when acetonitrile was in the system too. Resolution efficiency can be also increased by using the quasi-racemic resolving agent and thermodynamic control. Purification of enantiomeric mixtures was examined, and recrystallization of the diastereomeric salt was found to be the most efficient solution. Instructive behaviour of the complex enantiomer-conformer system of tofisopam is emphasized.

This presentation will focus on our recent progress in purifying enantiomeric pairs of DNA-wrapped carbon nanotubes (DNA-CNTs) via the aqueous two-phase extraction method. We will also discuss a potential application of enantiomeric pairs of DNA-CNTs in bilateral chiral sensing.

Optical resolution of several dialkyl-arylphosphine oxides was elaborated using the Ca2+ salt of (−)-O,O’-dibenzoyl-(2R,3R)-tartaric acid as the resolving agent. The conditions of crystallization and purification of the enantiomerically enriched phosphine oxides were optimized. Ethyl-phenyl-propylphosphine oxide and butyl-methyl-phenylphosphine oxide were prepared with an enantiomeric excess higher than 93%, whereas, three other dialkyl-arylphosphine oxides were obtained with an enantiomeric excess of 37–85%. It was also found that the sterically demanding alkyl chains hinder the formation of stable diastereomeric complexes, which consequently led to less efficient resolution procedures.

The optimization of enzymatic process for the resolution of chemically and pharmaceutically important racemic amines is described using a continuous flow bioreactor. Also described are the isolation and purification methods of the reaction products and the various parameters affecting the optimal reaction conditions for the enzymatic resolution to afford the products in high chemical purity and enantiomeric excess (ee) of over 90%.

La cristallisation est beaucoup utilisée pour isoler des molécules d’intérêt pharmaceutique sous formes énantiopures, ce qui nécessite que les énantiomère s’auto-discriminent à l’état solide. Malheureusement, ce comportement est imprévisible et rare (5-10%), car les deux énantiomères cristallisent majoritairement sous forme de composé racémique, empêchant toute résolution chirale par cristallisation. Réalisant que des conditions hors équilibres peuvent surmonter ces statistiques défavorables, nous avons exploré les comportements à l’état solide et les propriétés thermodynamiques de différentes séries de molécules analogues dérivées de trois composés model chiraux : le praziquantel, la proxyphylline, le paclobutrazol. Nos investigations ont conduit à trois approches clés pour améliorer les méthodes de résolution chirale par cristallisation : (i) une stratégie d’évolution dirigée basée sur les différences d’énergie entre les phases cristallines racémique et énantiopure, (ii) l’identification de caractéristiques moléculaires spécifiques favorisant la cristallisation de cristaux énantiopures et (iii) la conception d’une structure cristalline avec des capacités de discrimination chirale efficaces reposant sur une stratégie d’association hôte-invité. Ces avancées, reposant sur l’étude de dérivés chimiquement apparentés, ouvrent de nouvelles possibilités, précédemment inconsidérées, pour l’obtention d’énantiomères purs qui sont essentiels dans notre vie quotidienne
Crystallization is widely used for isolating biorelevant enantiopure molecules, which requires enantiomers to self-sort into separate enantiopure crystals. Unfortunately, this behaviour is unpredictable and rare (5-10%), as both enantiomers predominantly crystallize together into racemic crystals, hindering any such chiral sorting. Recognizing that non-equilibrium conditions may overcome these unfavourable statistics, we explored the solid-state landscapes and thermodynamic properties of different series of numerous analogous molecules derived from three distinct chiral cores: Praziquantel, Proxyphylline and Paclobutrazol. Our investigations led to three key approaches for enhancing crystallization-based chiral resolution methods: (i) A directed evolution strategy based on the energy differences between racemic and enantiopure crystal phases, (ii) the identification of specific molecular features favouring the crystallization of enantiopure crystals and (iii) engineering a crystal structure with efficient chiral discrimination capabilities that relies on a host-guest association strategy. These insights relying on the study of chemically related derivatives open new, previously unconsidered possibilities for isolating pure enantiomers that are essential in our daily lives

碩士
長庚大學
化工與材料工程學系
100
Stripping crystallization (SC) is introduced in this work for the purification of 3-phenyllactic acid and hydrobenzoin, both of which belong to the phase diagram forming conglomerates. In principle, SC is operated at a series of the three-phase equilibrium conditions, in which the liquid mixture is simultaneously vaporized and crystallized. Thus, SC combines distillation and crystallization to produce pure crystals. A thermodynamic model is developed to simulate the three-phase equilibrium during the SC operation and to direct the batch SC experiments. The experiments confirm that SC can be applied to purify (R,R)-hydrobenzoin from the chiral hydrobenzoin mixture. The experimental purity of final obtained product is consistent with the simulation result predicted by the model. However, the purification of 3-phenyllactic acid by Sc needs to be further investigated in the future work due to the possible polymerization occurred between hydroxyl group and carboxyl group among 3-phenyllactic acid.