Chiral separations

Rekoske, James E.

doi:10.1002/aic.690470102

Cited by 115 publications

(113 citation statements)

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“…3 Entre 1992 e 2000, o mercado mundial para compostos químicos opticamente puros aumentou de US$ 30 bilhões para uma estimativa de US$ 100 bilhões, com quase duas dúzias de companhias que se especializaram em separações quirais. 4 Em 2002, a venda mundial de medicamentos contendo um único enantiômero ultrapassou os US$ 159 bilhões, sendo que as duas drogas mais vendidas nesse mesmo ano, o Liptor e Zocor, renderam juntas US$ 14 bilhões. 5 Rekoske 4 relatou que entre as 500 drogas mais vendidas no mundo, 269 já estavam sendo comercializadas como um único enantiômero.…”

Section: Introductionunclassified

Separação cromatográfica quiral de anestésicos a partir de soluções diluídas e concentradas em escala preparativa

Silva¹,

Barreto²,

Santana³

2009

Quím. Nova

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Recebido em 3/3/08; aceito em 31/10/08; publicado na web em 2/2/09 CHIRAL CHROMATOGRAPHIC SEPARATION OF ANESTHETICS FROM DILUTE AND CONCENTRATED SOLUTIONS UNDER PREPARATIVE SCALE. In this work the separation of the chiral anesthetic compounds ketamine and bupivacaine was development using two chiral stationary phases (CSP). Ketamine enantiomers were well separate in the polysaccharide-based CSP (microcrystalline cellulose triacetate -MCTA) while bupivacaine in the tartardiamide-based CSP (Kromasil CHI-TBB). In both cases, the effect of temperature was investigated under analytical conditions. An improvement in the separation performance with temperature was observed. Thermodynamic parameters were evaluated by the van't Hoff plot. We concluded that enthalpic effects controlled the retention in these chiral columns. The enantiomers of ketamine and bupivacaine were separated under overloaded conditions with a good performance.Keywords: enantiomer separation; chiral stationary phases; liquid chromatography. introduçãoA separação de isômeros ópticos é importante para o desenvolvimento e a manufatura de numerosos terapêuticos. No intuito de conferir a composição dos fármacos, bem como estudos farmacocinéticos e clínicos mais elaborados, a habilidade para obter quantidades destes isômeros ópticos separadamente tornou-se de essencial importância. Muitos fármacos são administrados como uma mistura racêmica. No organismo, a maioria dos enantiômeros se comporta como duas entidades diferentes; processos controlados pela estereosseletividade, tais como absorção do fármaco, distribuição, metabolismo e eliminação, podem diferir substancialmente entre os enantiômeros. Como exemplo clássico da importância da quiralidade na indústria farmacêutica, podemos citar o caso da talidomida. Na década de 60, a talidomida foi comercializada na sua forma racêmica como um sedativo, para aliviar náuseas matinais em gestantes. Esse medicamento foi retirado do mercado após ter sido constatado apresentar sérios efeitos colaterais. Estudos posteriores confirmaram que apenas o R-enantiômero possui a atividade sedativa desejada, enquanto que o S-enantiômero apresenta propriedades teratogênicas, levando a deformações congênitas em fetos, quando administrado em gestantes.2 Durante a última década, houve grande interesse quanto à obtenção de enantiômeros em sua forma opticamente pura, devido a razões científicas e econômicas, sendo a indústria farmacêutica a principal interessada. 3 Entre 1992 e 2000, o mercado mundial para compostos químicos opticamente puros aumentou de US$ 30 bilhões para uma estimativa de US$ 100 bilhões, com quase duas dúzias de companhias que se especializaram em separações quirais. 5 Rekoske 4 relatou que entre as 500 drogas mais vendidas no mundo, 269 já estavam sendo comercializadas como um único enantiômero.A cromatografia é um processo de separação baseado no equilíbrio de distribuição dos componentes entre duas diferentes fases: a estacionária e a móvel. O transporte seletivo é o resultado da tendência do sistema para evol...

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Section: Introductionunclassified

Separação cromatográfica quiral de anestésicos a partir de soluções diluídas e concentradas em escala preparativa

Silva¹,

Barreto²,

Santana³

2009

Quím. Nova

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“…Recently, this technology has been brought into the field of fine chemistry and pharmaceutical industry [3].…”

Section: Introductionmentioning

confidence: 99%

Cyclic steady state of simulated moving bed processes for enantiomers separation

Minceva

Pais

Rodrigues

2003

Chemical Engineering and Processing: Process Intensification

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Simulated moving bed (SMB) technology developed by UOP in early 1960s has expanded greatly in the last decade, finding new applications in the area of natural products, fine chemistry and pharmaceutical industry. SMB processes are periodic processes designed to operate in cyclic steady state (CSS) and, therefore, the correct determination of CSS is needed for the assessment of the SMB performance. Two approaches can be used for determination of CSS: the dynamic simulation until CSS is reached and direct prediction of CSS. The direct prediction of CSS could be obtained in two ways: (i) considering that at CSS the spatially distributed SMB unit state at the end of the cycle is identical to that at its beginning (Method 1); or (ii) considering that at CSS the spatially distributed SMB unit state at the end of a switching time interval is identical to the state at the beginning of the interval, apart from a shift of exactly one column length (Method 2). The mathematical models assume axial dispersion flow and linear driving force (LDF) approximation for intraparticle mass transfer. Mathematical models were solved using the gPROMS (general Process Modelling System) software package. Both approaches (dynamic simulation and direct CSS prediction) were applied to the prediction of cyclic steady state of SMB unit for 1,1?-bi-2-naphthol enantiomers separation. The direct CSS predictions were compared with the standard dynamic simulation CSS prediction in terms of accuracy of SMB performance and computing time requirements; the Method 2 for CSS prediction is more efficient than the standard dynamic simulation. #

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“…The latter allows overcoming the problem associated with the yield limitation in chiral resolutions, where unwanted enantiomers are wasted. [8][9][10][11] A number of separation techniques can be used for the optical resolution. Among them chiral chromatography and enantioselective crystallization are considered the most straightforward, economical and easiest to perform on a large scale.…”

Section: Introductionmentioning

confidence: 99%

Separation of Stereoisomeric Mixtures of Nafronyl as a Representative of Compounds Possessing Two Stereogenic Centers By Coupling Crystallization, Diastereoisomeric Conversion and Chromatography

Kiwala

Olbrycht

Balawejder

et al. 2016

Org. Process Res. Dev.

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ABSTRACT:A procedure for the isolation of the most biologically active component of a stereoisomeric mixture of nafronyl -2-(diethylamino)ethyl 3-(naphthalen-1-yl)-2-((tetrahydrofuran-2-yl)methyl)propanoate, has been proposed. The molecule of nafronyl is a representative of compounds possessing two stereogenic centers, which may be produced in the form of a quaternary mixture that contains two pairs of racemates being diastereoisomers of one another. The components of such stereoisomeric mixtures usually differ in pharmacological activity, therefore, there is an interest in developing efficient methods for their resolution. The method suggested in this study comprised two sequential separation processes, including multistage cross-current crystallization and chiral chromatography.Crystallization was employed to enrich the raw material mixture with the target racemate, which contained the stereoisomer exhibiting the highest biological activity. To intensify the process, the mother liquors depleted with the target racemate were subjected to fast basecatalyzed diastereoisomeric conversion in melt, which provided equimolar mixtures of all four stereoisomers. The coupling of cross-current crystallization and diastereoisomeric conversion could improve yield of crystallization from 29% up to 84%. The purified racemate was further processed by chromatography to isolate finally the most active stereoisomer with 99% purity and total yield of 84%, at a relatively high throughput.

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Chiral separations

Cited by 115 publications

References 1 publication

Separação cromatográfica quiral de anestésicos a partir de soluções diluídas e concentradas em escala preparativa

Separação cromatográfica quiral de anestésicos a partir de soluções diluídas e concentradas em escala preparativa

Cyclic steady state of simulated moving bed processes for enantiomers separation

Separation of Stereoisomeric Mixtures of Nafronyl as a Representative of Compounds Possessing Two Stereogenic Centers By Coupling Crystallization, Diastereoisomeric Conversion and Chromatography

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