Enantioseparation of a chiral epoxide by simulated moving bed chromatography using Chiralcel-OD

Küsters, Ernst; Gerber, G.; Antia, Firoz D.

doi:10.1007/bf02269900

Cited by 57 publications

(23 citation statements)

References 6 publications

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“…the influence of the switch time period on the SMB performance. [82]. An eight-column configuration eventually due to experimental conditions such as was used and the operation temperature was fixed at small variations in flow-rates or column packings.…”

Section: IImentioning

confidence: 99%

Separation of enantiomers of a chiral epoxide by simulated moving bed chromatography

Pais

Loureiro

Rodrigues

1998

Journal of Chromatography A

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The paper deals with chiral separation by simulated moving bed (SMB) chromatography. The separation of chiral epoxide enantiomers in microcrystalline cellulose triacetate using methanol as eluent is considered as illustrative example. The use of microcrystalline cellulose triacetate for the chromatographic separation of enantiomers is first reviewed and a methodology for obtaining basic data (adsorption equilibrium isotherms, axial dispersion and mass transfer coefficient) is discussed. A model for the prediction of the cyclic steady-state performance of the SMB, based on the analogy with the true moving bed, is developed assuming multicomponent adsorption equilibria, axial dispersion flow and linear driving force approximation to describe the intraparticle mass transfer rate. The simulation package is used to predict the effect of operating variables on the process performance and to define the regions for enantiomer separation. A simple optimization procedure is proposed for choosing the best SMB operating conditions. This procedure is extensively tested for the separation of chiral epoxide enantiomers. The experimental operation of a SMB pilot unit was carried out for this system. Purities and recoveries higher than 90% were obtained for both extract and raffinate, using a 420 ml inventory of stationary phase. The SMB pilot allows the continuous resolution of 52 g of racemic mixture per day and per liter of bed, with a solvent consumption of 0.4 l of mobile phase per gram of racemic mixture processed. The simulation package is also used to predict the steady-state internal concentration profiles for the SMB operation with reasonable agreement with experimental results.

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Section: IImentioning

confidence: 99%

Separation of enantiomers of a chiral epoxide by simulated moving bed chromatography

Pais

Loureiro

Rodrigues

1998

Journal of Chromatography A

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“…SMC may become an especially useful technique in those preparative cases where only partial resolution is obtained rather quickly, and it is deemed by the chromatographer more efficient to use a column switching approach than to exhaustively study stationary phases, solvents, and additives to achieve ideal preparative separation conditions, or to use SMB. [264][265][266][267][268][269][270][271] A novel strategy for rapid chiral method development uses multicolumn parallel screening and circular dichroism signal pooling to shorten chiral method development by at least one-fifth of the time. 272 This approach splits the injection of one sample of racemate and pumps the split sample in parallel through at least five different chiral stationary phases followed by an equal number of UV detectors.…”

Section: Current Toolbox-chiral Separationsmentioning

confidence: 99%

Enantiomeric separation and determination of absolute stereochemistry of asymmetric molecules in drug discovery—Building chiral technology toolboxes

McConnell¹,

Bach

Balibar³

et al. 2007

Chirality

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The application of Chiral Technology, or the (extensive) use of techniques or tools for the determination of absolute stereochemistry and the enantiomeric or chiral separation of racemic small molecule potential lead compounds, has been critical to successfully discovering and developing chiral drugs in the pharmaceutical industry. This has been due to the rapid increase over the past 10-15 years in potential drug candidates containing one or more asymmetric centers. Based on the experiences of one pharmaceutical company, a summary of the establishment of a Chiral Technology toolbox, including the implementation of known tools as well as the design, development, and implementation of new Chiral Technology tools, is provided.

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“…The results of the calculations are summarized in Table I racemate (360 days of chromatography). Several investigations published in the literature deal with enantioseparations performed in an SMB system in comparison with conventional batch elution chromatography [9][10][11].…”

Section: Preparative Considerationsmentioning

confidence: 99%

The preparative chromatographic enantioseparation of a racemic morphanthridine analog on a chiral stationary phase

Küsters

Nozulak

1998

Chromatographia

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Key WordsColumn liquid chromatography Preparative scale separations Chiral stationary phase Enantiomer separation Morphanthridine analog SummaryThe preparative chromatographic enantioseparation of a chiral morphanthridine analog has been performed on an analytical column using amylose-tris(3,5-dimethylphenylcarbamate) as chiral stationary phase. The racemate (100 mg) was resolved to baseline within 15 min. This paper describes the development of the method, estimation of the capacity of the chiral stationary phase and discusses the potential of the chromatography if performed under preparative conditions. From the resuits and calculations presented it seems likely that the resolution of 70 tons year -1 could easily be achieved on 30 kg of stationary phase with a mobile-phase consumption of only 720 L day -1. resolution of which on a CSP seemed likely to be highly effective. It is the purpose of this communication to introduce this enantioseparation on a commercially available CSP and to discuss the potential of the chromatography if performed under preparative conditions. ExperimentalA Hewlett-Packard 1050 HPLC system was used for chromatography. Chiralpak-AD was purchased from Daicel Chemical Industries (Tokyo, Japan). The solvents used for the preparation of the mobile phases were LiChrosolv grade from Merck (Darmstadt, Germany). The mobile phase composition and chromatographic conditions are given in the captions to Figures 2 and 3.Dead time (tm) was estimated by use of 1,3,5-tri-tertbutylbenzene. The capacity factor, k, was calculated from k = (tr -tm)/tm, the enantioselectivity, a, from a = k2/kl and the resolution factor, R, from R = 1.18(t2 -tl)/(Wl(0.5) + W2(0.5)), where kl and k2 and tl and t2 refer to the capacity factors and retention times of the first and second eluted enantiomers and Wl(0.5) and W2(0.5) are the corresponding peak widths at half-height.

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Enantioseparation of a chiral epoxide by simulated moving bed chromatography using Chiralcel-OD

Cited by 57 publications

References 6 publications

Separation of enantiomers of a chiral epoxide by simulated moving bed chromatography

Separation of enantiomers of a chiral epoxide by simulated moving bed chromatography

Enantiomeric separation and determination of absolute stereochemistry of asymmetric molecules in drug discovery—Building chiral technology toolboxes

The preparative chromatographic enantioseparation of a racemic morphanthridine analog on a chiral stationary phase

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