Chiralpak

Another type of synthetic polymer-based chiral stationary phase is formed when chiral catalyst are used to initiate the polymerisation. In the case of poly(methyl methacrylate) polymers, introduced by Okamoto, the chiraUty of the polymer arises from the heUcity of the polymer and not from any inherent chirahty of the individual monomeric subunits (109). Columns of this type (eg, Chiralpak OT) are available from Chiral Technologies, Inc., or J. T. Baker Inc. 

Chiralpak AD Amylose U is(3,5-dimetltylphenylcarbamate) coated on silica gel [19,69] Daicel... 

Chiralpak AD Amylose tris(3,5-dimethylphenylcarbamate) coated on amino-propyl silica. 

To demonstrate the excellent correlation (r- = 0.99) between the luminance of the images and molecular diversity, we plotted the luminance values of the map versus the mean similarity values of data sets (Fig. 4-13). From this plot, a scoring scheme for the classification of CSPs from specific to broad application range can be well established Crownpak CR > Pirkle DNBPG > Whelk > Chiralpak AD > Chiralcel OD. 

Chiralcel OD and Chiralpak AD are associated with the largest mean values of molecular diversity. 

The purpose of this study is only intended to illustrate and evaluate the decision tree approach for CSP prediction using as attributes the 166 molecular keys publicly available in ISIS. This assay was carried out a CHIRBASE file of 3000 molecular structures corresponding to a list of samples resolved with an a value superior to 1.8. For each solute, we have picked in CHIRBASE the traded CSP providing the highest enantioselectivity. This procedure leads to a total selection of 18 CSPs commercially available under the following names Chiralpak AD [28], Chiral-AGP [40], Chiralpak AS [28], Resolvosil BSA-7 [41], Chiral-CBH [40], CTA-I (microcrystalline cellulose triacetate) [42], Chirobiotic T [43], Crownpak CR(-i-) [28], Cyclobond I [43], DNB-Leucine covalent [29], DNB-Phenylglycine covalent [29], Chiralcel OB [28], Chiralcel OD [28], Chiralcel OJ [28], Chiralpak OT(-i-) [28], Ultron-ES-OVM [44], Whelk-0 1 [29], (/ ,/ )-(3-Gem 1 [29]. 

However, it has provided some interesting results. At the top of the tree, the molecule population is first divided according to the presence or absence of the attribute NH2 (primary amine). If the answer is yes , the developed branches (on the right of the tree) mostly leads to the Crownpak CSP. The next attribute is Aromatic . If the answer is no , here the predominant CSP is Chiralpak AD. Aromatic compounds form the largest part of the tree and as expected the dominant CSP is Chiralcel OD which is disseminated in almost every region of the tree. 

Chiralpak OT(+) dominates the branches built under the spiro and AROMATIC RING>1 molecular keys. 

The latter approach is used in the enantioselective determination of a Phase I metabolite of the antihistaminic drug, terfenadine. Terfenadine is metabolized to several Phase I compounds (Fig. 7-13), among which the carboxylic acid MDL 16.455 is an active metabolite for which plasma concentrations must often be determined. Although terfenadine can be separated directly on Chiralpak AD - an amy-lose-based CSP - the adsorption of the metabolite MDL 16.455 is too high to permit adequate resolution. By derivatizing the plasma sample with diazomethane, the carboxylic acid is converted selectively to the methyl ester, which can be separated in the presence of all other plasma compounds on the above-mentioned CSP Chiralpak AD [24] (Fig. 7-14). Recently, MDL 16.455 has been introduced as a new antihistaminic drug, fexofenadine. 

Fig. 7-14. Separation of terfenadine and MDL 16,455 methyl ester on Chiralpak AD , (a) Terfenadine Chiralpak AD 250-4.6, w-hexane/2-propanol (90 10), flowrate 1.0 ml min, UV-detection 224 nm. (b) MDL 16,455 methyl ester Chiralpak AD 250-4.6, w-hexane/2-propanol (90 10), flowrate 1.0 ml min , UV-detec-tion 224 nm. (Reproduced with permission from A. Terhechte, PhD Thesis, University of Munster, Munster, 1993 [24].)...

Fig. 12-3. Separation of ingredients of an expeetorant syrup, on a Chiralpak AD CSP (a) and the eoupled eyano/Chiralpak AD CSP (b). Chromatographie eonditions 10 % methanol with 0.5 % isopropylamine in earbon dioxide, 2.0 mL min, 15 MPa, 30 °C. Peaks are benzole aeid (BA), guaifenesin (GF), and phenylpropanolamine (PPA).

Derivatized amylose is the basis for the Chiralpak AD CSP. This CSP has been utilized for the resolution of ibuprofen and flurbiprofen, as well as other members of the family of nonsteroidal inflammatory drugs (NSAIDs) [39, 61]. Ibuprofen was not resolved on the Chiralpak AD CSP in LC. Pressure-related effects on stereoselectivity were observed by Bargmann-Leyder et al. on a Chiralpak AD CSP [58]. No corresponding effect of pressure on selectivity was observed with a Chiralcel OD CSP. The authors speculated that the helical conformation of the amylose-based CSP is more flexible than that of the cellulose-based CSP. 

Macaudiere and co-workers performed a comparison of LC and SFC on a polymer based-CSP (Chiralpak OT) [64]. The chromatographic behavior of this CSP seemed to be quite different in SFC than in LC, although satisfactory separations were achieved with both techniques. The chiral recognition mechanisms may be altered by the nature (hexane-based or CO,-based) of the eluent. 

Enantiomeric excesses were determined by chiral HPLC on ChiralPak AD (Hexane 2-PiOH 75 25). 

Ferretti et al. (1988) used an amino column coupled to a derivatized amylose column (Chiralpak AS) operated in the reverse-phase mode to separate the enantiomers of the antifungal agent voriconazole from several chiral impurities and one achiral impurity. Three of the chiral impurities are the other enantiomer and corresponding diastereomers of voriconazole. More chiral impurities result from a chlorinated voriconazole. Additionally, this multidimensional method could baseline separate all but two of the chiral impurities into their respective enantiomers. These separations are shown in Figure 14.5. 

FIGURE 14.5 Separations involving voriconazole (1), its mirror image (2), related diaster-eomers (3), chlorinated impurities (4), and an achiral impurity 5. (a) Achiral separation of compounds 1-5 on an amino column with hexane/ethanol mobile phase (b) Chiral separation of compounds 1-5 on Chiralpak As column with hexane/ethanol mobile phase (c) Achiral-chiral multidimensional separation with the amino and chiral column coupled in series. Reprinted from Ferretti et al. (1998) with permission from Vieweg Verlag. 

Achiral-chiral chromatography has also been accomplished using subcritical fluid chromatography (Phinney et al., 1998). In this work, the structurally related [3-blockers, 1,4-benzodiazepines, and two cold medicines were separated using methanol or ethanol modified carbon dioxide mobile phases. The (3-blockers were separated using cyanopropyl and Chiracel OD columns connected in series. Likewise, an amino bonded phase and Chiracel OD column were used for the separation of the 1,4-benzodiazepines. Guaifenesin and phenylpropanolamine from cough syrup were separated on cyanopropyl and Chiralpak AD columns in series. 

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. 

Fig. 14A-C Chromatography of the racemic monoepoxy derivatives (I—III) of Z3,Z6,Z9-18 on chiral HPLC columns A Chiralpak AD B Chiralpak AS C Chiralcel OJ-R. The solvent system for the former two normal-phase columns is 0.1% 2-propanol in n-hexane (0.45 ml/min), and that of the third column is 15% water in MeOH (0.45 ml/min). Homo-conjugated dienes, epo3,Z6,Z9-18 H (I) and Z3,Z6,epo9-18 H (III), were detected by UV (215 nm), and Z3,epo6,Z9-18 H (II) was detected by RID. The earlier eluting isomers have a 3S,4R, 6S,7R, or 9R,10S configuration...

Aboul-Enein and Ali [78] compared the chiral resolution of miconazole and two other azole compounds by high performance liquid chromatography using normal-phase amylose chiral stationary phases. The resolution of the enantiomers of ( )-econazole, ( )-miconazole, and (i)-sulconazole was achieved on different normal-phase chiral amylose columns, Chiralpak AD, AS, and AR. The mobile phase used was hexane-isopropanol-diethylamine (400 99 1). The flow rates of the mobile phase used were 0.50 and 1 mL/min. The separation factor (a) values for the resolved enantiomers of econazole, miconazole, and sulconazole in the chiral phases were in the range 1.63-1.04 the resolution factors Rs values varied from 5.68 to 0.32. 

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