Supercritical fluid chromatography enantioseparation

This review provides an overview of the literature published to date on macrocyclic antibiotics exploited for enantioselective separations in high-performance liquid chromatography (HPLC). It was not intended as a comprehensive issue on the applications of such antibiotics in sub- and supercritical fluid chromatography (SFC), thin layer chromatography (TLC), capillary electrophoresis (CE), and capillary electrochromatography (CEC). A number of structural properties of the most important macrocyclic antibiotics applied in HPLC enantioseparations are listed in Table 2.1. 

Enantioselective separation by supercritical fluid chromatography (SFC) has been a field of great progress since the first demonstration of a chiral separation by SFC in the 1980s. The unique properties of supercritical fluids make packed column SFC the most favorable choice for fast enantiomeric separation among all of the separation techniques. In this chapter, the effect of chiral stationary phases, modifiers, and additives on enantioseparation are discussed in terms of speed and resolution in SFC. Fundamental considerations and thermodynamic aspects are also presented. 

A polar stationary phases such as ODS and TMS and polar such as CN, diol, or NO2 have been successfully applied to the separation of monosaccharides Separation of maltodextrin derivatized with trifluoroacetic anhydride using FID and a CN packed column Capillary supercritical fluid chromatography-MS is well suited to confirm the identity of the TMS derivative of inositol triphosphate Chiral analytes Enantioseparation... 

The majority of enantioseparations are performed by pressure-driven liquid chromatography. However, in the last decade other liquid-phase separation techniques have evolved and demonstrated their usefulness for enantioseparations, including supercritical fluid chromatography (SFC), capillary electrophoresis (CE), micellar electrokinetic chromatography (MEKC), and open-tubular and packed-bed electrochromatography (OT-EC and CEC). 

TLC has also been used for the separation of diastereomeric derivatives of enantiomers, but this form of chromatography has not attained widespread use in indirect resolutions. Other chromatographic techniques, for example, supercritical fluid chromatography, capillary electrophoresis, countercurrent chromatography, etc., have not received much attention in indirect enantioseparation. 

A further evaluation of the CB-DNP was reported by Gahm of Amgen using supercritical fluid chromatography (SFC) [27]. He concluded that inclusion com-plexation was the primary factor in retention and enantioselectivity. Better enantioseparation, as well as peak shape together with the reversal of elution order, makes CD-based CSPs unique and complimentary to the more commonly used jt-basic amylose and cellulose columns. 

Fig. 16 Enantioseparation of a small molecule MDM2 antagonist Nuthn-3 and its enantiomer under (a) reversed phase, (b) polar organic, (c) normal phase, and (d) supercritical fluid chromatography conditions. Time in min (adapted from [170])...

This database contains information about CSPs and conditions for HPLC and supercritical fluid chromatography (SFC) enantioseparations for more than 50,000 products. It is regularly updated by Prof. Christian Roussel and Dr. Patrick Piras (Aix-Marseille Universite, France) with published and unpublished results. ChirBase contains also conditions for GC and CE enantioseparations, which are updated by the group led by Prof. B. Koppenhoefer (University of Tubingen, Germany). 

De Klerck K, Mangelings D, Vander Heyden Y. Supercritical fluid chromatography for the enantioseparation of pharmaceuticals. J. Pharm. Biomed. Anal. 2012 69 77-92. 

G. Enantioseparation of 1-phenyl-1-propanol by supercritical fluid-simulated moving bed chromatography. J. Chromatogr. A, 2005,1092 (1), 55-64. 

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