Chiral separation with advantages

Analysis using a CMPA is usually resolved on a nonchiral column. A transient diastereomeric complex is formed between the enantiomer and the chiral component in the mobile phase, similar to the complexes formed with chiral stationary phases. A review by Liu and Liu (2002) cites several papers where addition of CPMAs has been used in analyzing amphetamine-related compounds. Some CPMAs include amino acid enantiomers, metal ions, proteins, and cyclodextrins. Advantages of this method of analysis include the use of less expensive columns and more flexibility in the optimization of chiral separation (Misl anova and Hutta, 2003). 

The indirect approach has been widely applied since many functional groups can be derivatized with various chiral reagents and the covalent diastereoisomers can be separated with inexpensive non-chiral systems. Other advantages of the indirect approach are that method development is rather straightforward and that the detection sensitivity of the enantiomers can be improved by the selection of an appropriate CDR having a strong chromophor or fluorophor. 

On the basis of this discussion a particularly promising scheme for synthesizing chiral compounds with great isomer purity and high overall yield would be to start with a productive asymmetric synthesis (to assure high yield) and follow by a destructive one (to assure unlimited isomer purity of the desired product). Such a procedure has the essential advantage that under suitable conditions it leads to pure chiral compounds without cumbersome separation of stereoisomers. With proper choice of the reactants the procedure will also permit an effective recovery of the auxiliary chiral materials needed as chiral templates in the asymmetric synthesis. 

Polysaccharide derivatives used as CSPs interact with chiral analytes in much the same manner as cyclodextrins. These molecules have been shown to exhibit high chiral recognition ability in HPLC [155]. The main advantage of CEC over HPLC is the enhanced efficiency. In chiral separations, slow mass transfer kinetics between the CSP and chiral analytes have somewhat diminished the efficiency advantage of the technique. The goal of using polysaccharide derivatives... 

Indirect approaches such as chiral derivatization with chiral derivatizing reagents (CDR) offers a variety of advantages. For instance, CDRs are cheaper than chiral columns. Separation of the product diastereomers is generally more flexible than the corresponding enantiomeric separation because achiral columns can be used in conjunction with various mobile-phase... 

Conversely, the use of chiral mobile phases has advantages which make it very appealing. Many chiral additives are readily available or can be easily synthesized. Achiral stationary phases, which are significantly cheaper than chiral phases, can be used. The approach also offers more flexibility than direct separation with chiral stationary phases because the chiral mobile phase additives can often be easily washed out of the chromatographic system and replaced with another additive for subsequent separations. 

For enantioseparation on CSPs in CEC, nonstereospecific interactions, expressed as 4>K, contribute only to the denominator as shown in Eq. (1), indicating that any nonstereospecific interaction with the stationary phase is detrimental to the chiral separation. This conclusion is identical to that obtained from most theoretical models in HPLC. However, for separation with a chiral mobile phase, (pK appears in both the numerator and denominator [Eq. (2)]. A suitable (f)K is advantageous to the improvement of enantioselectivity in this separation mode. It is interesting to compare the enantioselectivity in conventional capillary electrophoresis with that in CEC. For the chiral separation of salsolinols using /3-CyD as a chiral selector in conventional capillary electrophoresis, a plate number of 178,464 is required for a resolution of 1.5. With CEC (i.e., 4>K = 10), the required plate number is only 5976 for the same resolution [10]. For PD-CEC, the column plate number is sacrificed due to the introduction of hydrodynamic flow, but the increased selectivity markedly reduces the requirement for the column efficiency. 

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