Chiral cyclodextrin-type

It is in the study of this phenomenon where two-dimensional GC offers by far the most superior method of analysis. The use of chiral selector stationary phases, in particular modified cyclodextrin types, allows apolar primary and atropisomer selective secondary separation. Reported two-dimensional methods have been successful... 

A chiral GC column is able to separate enantiomers of epoxy pheromones in the Type II class, but the applications are very limited as follows a custom-made column packed with a p-cyclodextrin derivative as a liquid phase for the stereochemical identification of natural 3,4- and 6,7-epoxydienes [73, 74] and a commercialized column of an a-cyclodextrin type (Chiraldex A-PH) for the 3,4-epoxydiene [71] (See Table 3). The resolution abilities of chiral HPLC columns have been examined in detail, as shown in Table 7 and Fig. 14 [75,76, 179]. The Chiralpak AD column operated under a normal-phase condition separates well two enantiomers of 9,10-epoxydienes, 6,7-epoxymonoenes and 9,10-epoxymonoenes. Another normal-phase column, the Chiralpak AS column, is suitable for the resolution of the 3,4-epoxydienes. The Chiralcel OJ-R column operated under a reversed-phase condition sufficiently accomplishes enantiomeric separation of the 6,7-epoxydienes and 6,7-epoxymonoenes. 

Another approach is electrochromatography with capillary columns packed with an achiral stationary phase, preferentially a reversed-phase type material. The chiral SO is added to the background electrolyte, and may be adsorbed onto the stationary phase by a secondary equilibration process. Enantioseparations in this additive mode have been reported with cyclodextrin type SOs )504-507) and with a chiral ion-pair agent derived from quinine 1508) as mobile phase additives. 

Fig. 2 Influence of cyclodextrin type on the chiral resolution of the basic drug tocainide and related substances using 40 mM sodium phosphate (pH 3.0) containing (a) 20 mM -CD and (b) 50 mM methyl- -CD and 50 mM heptakis (2,6 di-O-methyl-jS-CD. [Adopted with kind permission from D. Beider and G. Schomburg, Chiral separations of basic and acidic compounds in modified capillaries using cyclodextrin-modified capillary zone electrophoresis, J. Chromatogr. A 666 351 (1994).]...

Chiral separations can be carried out using an amino acid-based or a cyclodextrin-type (Section 3.5.5.2) stationary phase. The latter is most common, and the selectivity is based on surface interactions or inclusion. Usually rather low temperatures are used as enantioselectivity is rare above 200 °C. Because of higher plate numbers, capillary GC columns generally give better enantiomeric separations than HPLC columns. 

Chankvetadze B, Buijanadze N, Crommen 1, Blaschke G (2001) Enantioseparation of warfarin using cyclodextrin type chiral selectors. Chromatographia 53 S296-S301... 

Grafting a receptor moiety onto rare earth metal complexes led to a new series of CSRs operating in water. Dy + complexes with cyclodextrin derivatives 75 (scheme 16) were synthesized as Itybrid-type CSRs in which the triaminotetracarboxylic acid moiety chelates the rare earth ion while the chiral cyclodextrin accommodates aromatic compounds in its hydrophobic pocket (Wenzel et al., 1994, 2000). Wenzel et al. (2003) demonstrated that the commercially available sulfonated and carboxymethylated cyclodextrins are effective CSRs for water-soluble aromatic cations in the presence of Dy + or Yb " ". A crown ether derivative, which accommodates primary ammonium cations, also forms chelates with rare earth... 

Figure 3.7 shows some early examples of this type of analysis (39), illustrating the GC determination of the stereoisomeric composition of lactones in (a) a fruit drink (where the ratio is racemic, and the lactone is added artificially) and (b) a yoghurt, where the non-racemic ratio indicates no adulteration. Technically, this separation was enabled on a short 10 m slightly polar primary column coupled to a chiral selective cyclodextrin secondary column. Both columns were independently temperature controlled and the transfer cut performed by using a Deans switch, with a backflush of the primary column following the heart-cut. 

GC using chiral columns coated with derivatized cyclodextrin is the analytical technique most frequently employed for the determination of the enantiomeric ratio of volatile compounds. Food products, as well as flavours and fragrances, are usually very complex matrices, so direct GC analysis of the enantiomeric ratio of certain components is usually difficult. Often, the components of interest are present in trace amounts and problems of peak overlap may occur. The literature reports many examples of the use of multidimensional gas chromatography with a combination of a non-chiral pre-column and a chiral analytical column for this type of analysis. 

The type of CSPs used have to fulfil the same requirements (resistance, loadabil-ity) as do classical chiral HPLC separations at preparative level [99], although different particle size silica supports are sometimes needed [10]. Again, to date the polysaccharide-derived CSPs have been the most studied in SMB systems, and a large number of racemic compounds have been successfully resolved in this way [95-98, 100-108]. Nevertheless, some applications can also be found with CSPs derived from polyacrylamides [11], Pirkle-type chiral selectors [10] and cyclodextrin derivatives [109]. A system to evaporate the collected fractions and to recover and recycle solvent is sometimes coupled to the SMB. In this context the application of the technique to gas can be advantageous in some cases because this part of the process can be omitted [109]. 

Mourier s report was quickly followed by successful enantiomeric resolutions on stationary phases bearing other types of chiral selectors, including native and deriva-tized cyclodextrins and derivatized polysaccharides. Many chiral compounds of pharmaceutical interest have now been resolved by packed column SFC, including antimalarials, (3-blockers, and antivirals. A summary is provided in Table 12-2. Most of the applications have utilized modified CO, as the eluent. 

Many racemic mixtures can be separated by ordinary reverse phase columns by adding a suitable chiral reagent to the mobile phase. If the material is adsorbed strongly on the stationary phase then selectivity will reside in the stationary phase, if the reagent is predominantly in the mobile phase then the chiral selectivity will remain in the mobile phase. Examples of some suitable additives are camphor sulphonic acid (10) and quinine (11). Chiral selectivity can also be achieved by bonding chirally selective compounds to silica in much the same way as a reverse phase. A example of this type of chiral stationary phase is afforded by the cyclodextrins. 

The more useful types of chirally active bonded phases are those based on the cyclodextrins. There are a number of different types available, some of which have both dispersive or polar groups bonded close to the chirally active sites to permit mixed interactions to occur. This emphasizes the basic entropic differences between the two isomers being separated. A range of such products is available from ASTEC Inc. and a separation of the d and / isomers of scopolamine and phenylephrine are shown in figure 4. The separations were carried out on a cyclodextrin bonded phase (CYCLOBOND 1 Ac) that had been acetylated to provide semi-polar interacting groups in close proximity to the chiral centers of the cyclodextrin. The column was 25 cm long, 4.6 mm in diameter and packed with silica based spherical bonded phase particles 5pm in diameter. Most of the columns supplied by ASTEC Inc. have these dimensions and, consequently, provide a... 

There is a wide variety of commercially available chiral stationary phases and mobile phase additives.32 34 Preparative scale separations have been performed on the gram scale.32 Many stationary phases are based on chiral polymers such as cellulose or methacrylate, proteins such as human serum albumin or acid glycoprotein, Pirkle-type phases (often based on amino acids), or cyclodextrins. A typical application of a Pirkle phase column was the use of a N-(3,5-dinitrobenzyl)-a-amino phosphonate to synthesize several functionalized chiral stationary phases to separate enantiomers of... 

An understanding of the recognition of chirality at a molecular level has become of interest in many fields of chemistry and biology. In the past decade, many attempts to clarify the mechanism of chiral recognition on CSPs for liquid chromatography have been made by means of chromatography, NMR spectroscopy,199 202 X-ray analysis, and computational methods.203 - 206 The successful studies have been mostly carried out for the small-molecule CSPs, especially cyclodextrin-based CSPs and Pirkle-type (brush-type) CSPs. In contrast, only a few mechanistic studies on chiral discrimination at the molecular... 

Many chiral compounds can be used as selectors, for example, chiral metal complexes, native and modified cyclodextrins, crown ethers, macrocyclic antibiotics, noncyclic oligosaccharides, and polysaccharides all have been shown to be useful for efficient separation of different types of compounds. 

The PO mode is a specific elution condition in HPLC enantiomer separation, which has received remarkable popularity especially for macrocyclic antibiotics CSPs and cyclodextrin-based CSPs. It is also applicable and often preferred over RP and NP modes for the separation of chiral acids on the cinchonan carbamate-type CSPs. The beneficial characteristics of the PO mode may arise from (i) the offset of nonspecific hydrophobic interactions, (ii) the faster elution speed, (iii) sometimes enhanced enan-tioselectivities, (iv) favorable peak shapes due to improved diffusive mass transfer in the intraparticulate pores, and last but not least, (v) less stress to the column, which may extend the column lifetime. Hence, it is rational to start separation attempts with such elution conditions. Typical eluents are composed of methanol, acetonitrile (ACN), or methanol-acetonitrile mixtures and to account for the ion-exchange retention mechanism the addition of a competitor acid that acts also as counterion (e.g., 0.5-2% glacial acetic acid or 0.1% formic acid) is required. A good choice for initial tests turned out to be a mobile phase being composed of methanol-glacial acetic acid-ammonium acetate (98 2 0.5 v/v/w). 

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