Flow enantioseparation

In a different approach, Stalcup and co-workers [25] used sulfated (3-cyclodextrin for the enantioseparation of piperoxan in work directly derived from earlier CE and classical gel results. Their results were obtained using a continuous free flow apparatus developed by R S Technologies, Inc. Processing rates on the order of 4.5 mg h were reported. 

Figure 3.12 Enantioseparation of TrOger s base on (a) microcrystalline cellulose triacetate (CTA I) and (b) 21 coated on silica gel. Column, 25 x 0.46 (i.d.) cm eluent ethanol-HoO (7/3) flow rate, 0.5 ml/min).

Figure 3.21 Enantioseparation of 2-(benzylsulfinyl)benzamide on 23aa using 2-propanol as an eluent. Column 25 x 0.46 (i.d.) cm flow rate 0.5 ml/min. (Reprinted with permission from Ref. 165. Copyright 2000 by the Chemical Society of Japan.)...

A strategy for the enantioseparation of basic compounds was described by SokolieP and Koller [35] and is displayed in Figure 3.7. All steps from method development till validation are included in the flow chart. Perhaps a disadvantage in this approach is that sequential screening and optimization steps are used (i.e., every factor is optimized individually). The use of the developed scheme was demonstrated for one compound, for which the method was developed, optimized, and validated. The generic applicability of this approach was not considered and is unknown. 

The use of a convective macroporous polymer as an alternative support material instead of silica for the preparation of protein-based CSPs has successfully been demonstrated by Hofstetter et al. [221]. Enantioseparation was performed using a polymeric flow-through-type chromatographic support (POROS-EP, 20 pm polymer particles with epoxy functionalities) and covalently bound BSA as chiral SO. Using flow rates of up to 10 ml/min, rapid enantiomer separation of acidic compounds, including a variety of amino acid derivatives and drugs, could be achieved within a few minutes at medium efficiencies, typical for protein chiral stationary phases (Fig. 9.13). 

Because solutes have higher diffusion coefficients in super(sub)critical fluids than in liquids, the optimum linear velocity is shifted to higher values. Consequently, higher flow rates can be used leading to reduced analysis (separation) time without compromising efficiency. In addition, although the chiral discrimination ability of CSPs and enan-tioselectivity in SFC resemble usually those of non-aqueous LC, in some cases enantioseparations can be obtained in SFC which cannot be achieved in conventional LC. 

More recently, capillary electrochromatography (CEC) has been adapted for enantioseparation concepts. In this separation method, the driving force for solute transport through the capillary columns is the electroosmotic flow (EOF) in addition, for charged SAs, an electrophoretic transport increment has also to be considered. The enantioseparation occurs due to differential distribution of the SA-enantiomers to the immobilized chiral SO moieties, or in the additive mode due to differential migration of diastere-omeric SO-SA a.ssociates and/or their differential distribution onto an achiral stationary phase. Thus, the following strategies have been adopted for CEC enantioseparations,... 

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. 

Figure 13.19 HPLC enantioseparation of racemic dichloroprop 43 on the (DHQD)2PHAL-type CSP (61). Column (150 mm X 4 mm i.d.) mobile phase methanol/acetic acid/ ammonium acetate (92 2 0.5, v/v/w) flow rate 1 ml/min UV detection 254 nm column temperature 25 °C [108].

Enantioseparation of SB-553261 racemate using SMB technology Three cases (a) maximizing the purity and productivity of raffirrate stream, (b) maximization of purity and productivity of extract stream, and (c) maximization of feed flow rate and minimization of desorbent flow rate. NSGA-n-JG Both SMB and Varicol processes were optimized, and the study found that the latter has superior performance. Wongsoc/fll. (2004)... 

Glycopeptide antibiotics have been found to be very effective chiral selectors in the enantiomeric separation of racemic pharmaceutical compounds. Vancomycin, ristocetin A, rifamycins, teicoplanin, kanamycin, streptomycin, and avoparcin have been added to the running buffer to obtain enantioseparation (161,203— 207). A few technical modifications, such as coated capillaries and separation conditions in the reverse polarity mode (as opposed to normal polarity mode, where the flow is from anode to cathode) were found to improve sensitivity and increase efficiency (116,208). 

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