Direct chiral separations

This separation is an impressive example of an entropically driven distribution system where the normally random movements of the solute molecules are restricted to different extents depending on the spatial orientation of the substituent groups. For further information the reader is directed to an excellent review of chiral separations by LC (Taylor and Maher (12)) and a monograph on CYCLOBOND materials from ASTEC Inc. (13). 

Torok, G. et al.. Direct chiral separation of unnatural amino acids by high performance liquid chromatography on a ristocetin A-bonded stationary phase. Chirality, 13, 648, 2001. 

Chiral separation of drng molecules and of their precursors, in the case of synthesis of enantiomerically pure drugs, is one of the important application areas of HPLC in pharmaceutical analysis. Besides HPLC, capillary electrophoresis (CE) is another technique of choice for chiral separations. Chapter 18 provides an overview of the different modes (e.g., direct and indirect ones) of obtaining a chiral separation in HPLC and CE. The direct approaches, i.e., those where the compound of interest is not derivatized prior to separation, are discussed in more detail since they are cnrrently the most frequently used techniques. These approaches require the use of the so-called chiral selectors to enable enantioselective recognition and enantiomeric separation. Many different molecnles have been nsed as chiral selectors, both in HPLC and CE. They can be classified into three different groups, based on their... 

A. Principles of Chiral Separation in LC Direct and Indirect Approaches... 

A general comment about detection in chiral separations, both direct and indirect, is that in general all detectors used for non-chiral separations can also be used. The most frequently applied detector is thus the UV detector. 

An extremely important aspect in pharmaceutical research is the determination of drug optical purity. The most frequently applied technique for chiral separations in CZE remains the so-called dynamic mode where resolution of enantiomers is carried out by adding a chiral selector directly into the BGE for in situ formation of diastereomeric derivatives. Various additives, such as cyclodextrins (CD), chiral crown ethers, proteins, antibiotics, bile salts, chiral micelles, and ergot alkaloids, are reported as chiral selectors in the literature, but CDs are by far the selectors most widely used in chiral CE. 

Li, S., and Lloyd, D. K. (1993). Direct chiral separations by capillary electrophoresis using capillaries packed with an alpha(l)-acid glycoprotein chiral stationary phase. Anal. Chem. 65,... 

For the majority of the direct chiral separations in HPLC, different kinds of CSPs are used. The CSP can consist of small chiral molecules or polymers [22] and is often immobilized on agarose [23], silica gel [23,24], or polymer particles [23]. During the two last decades, a number of new phases have been introduced. Most commonly used CSPs are listed in Table 17.1. 

The Innovative Direction in Chiral Separations, Phenomenex, Torrance, USA (1992). 

H.-G. Schmarr, A. Mosandl and K. Grob, Stereoisomeric flavour compounds. XXXVIII direct chirospecific analysis of y-lactones using on-line coupled LC-GC with a chiral separation column , Chromatographia 29 125-130 (1990). 

Enantiomeric compounds cannot be separated directly in normal chromatographic systems since the groups attached to the chiral atom are equally accessible to binding. If the enantiomers are combined with a chiral selector (enantiomeric reagent), however, two diastereomers are formed that may... 

Capillary electrophoresis (CE) provides a valid alternative to HPLC methods for chiral separations. The direct resolution of racemates requires only an enantiomerically pure additive (chiral selector) to be dissolved in the running buffer. The experimental conditions affecting the separations and an overview of practical applications have been compiled <1999ELP2605>. 

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