Chiralcel Chiralpak

Application Guide for Chiral Column Selection Crownpak-Chiralcel-Chiralpak. Chiral HPLC Column for Optical Resolution. 2nd Ed.. Daicel Chemical Industries. Ltd.. Tokyo. 

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. 

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. 

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...

Thirdly, a screening approach (Figure 3.11a) was developed in another mode of liquid chromatography, i.e., polar organic solvent chromatography (POSC) [47]. The screening is executed sequentially on four polysaccharide columns, in the following order Chiralpak AD-RH, Chiralcel OD-RH, Chiralpak AS-RH, and finally, Chiralcel... 

Kennedy et al. [57] have described the use of an intelligent chiral resolution system using a rapid screening of conditions on polysaccharide CSP, aiming to transfer the separation to preparative LC afterward. For the analytical part of the strategy, lO-pm particles were used for the preparative section, the particles had a 20-ttm diameter. The screening performs 11 experiments on analytical columns, which are displayed in Table 3.3. Chiralpak AD, Chiralcel OD, Chiralcel OJ, and Chiralpak AS are the considered stationary phases, and they are analyzed either in POSC or NPLC mode. The... 

These polysaccharide-based stationary phases appear to be the most useful in organic, bio-organic and pharmaceutical analysis. Of the above-mentioned derivatives three of them, namely cellulose tris-(3,5-dimethylphenylcarbamate), amylose tris-(3,5-dimethylphenylcarbamate) and cellulose tris-(4-methylbenzoate), have very complementary properties and numerous publications have demonstrated that they have been able to achieve the chiral resolution of more than 80% of the drugs currently available on the market. " These CSPs are known under the commercial names, Chiralcel OD-H , Chiralpak AD and Chiralcel OJ , respectively (Figure 4). Their very broad enantiorecognition range is also the... 

FIGURE 5 Differences in selectivity obtained on Chiralcel OD-H, OJ and Chiralpak AD columns under NPLC conditions. Chromatographic conditions hexane/ethanol 90/10 (v/v) with 0.1% (v/v) diethylamine or trifluoroacetic acid for basic or acidic compounds, respectively. Flow rate I mL/min. 

Another screening strategy using the same type of columns but with normal-phase gradient elution has been proposed by the pharmaceutical group Lilly.In this strategy, each compound is screened on four columns, i.e., Chiralcel OD-H, Chiralpak AD, Chiralpak AS and Chiralcel OJ. An n-hexane/2-propanol and an n-hexane/EtOH gradient elution system are... 

FIGURE 9 Chiral separation of acebutolol using (a) the NPLC and (b) the RPLC strategies. Experimental conditions. NPLC stationary phase Chiralpak AD-H, mobile-phase composition hexane/EtOH/DEA (90/10/0.1), temperature 20°C and flow rate 1.0 mL/min RPLC Chiralcel AD-RH, 20mM borate buffer pH 9.O/CH3CN (60/40 v/v), room temperature, flow rate = 0.5 mL/min. 

Very recently, the pharmaceutical group Astra-Zeneca proposed a screening strategy involving the use of both polysaccharide and macrocyclic glycopeptide columns. It is proposed to screen the compounds on seven different columns Chiralcel OD-H, Chiralpak AD, Chiralpak AS, Chiralcel... 

Figure 3.1 Chemical structures of the current most successfully employed derivatised polysaccharide CSPs. (a) CHIRALPAK AD Amylose tris (3,5-dimethylphenylcarbamate) coated onto a silica support, (b) CHIRALPAK AS Amylose tris [(S)-a-methylbenzylcarbamate] coated onto a silica support, (c) CHIRALCEL OD Cellulose tris (3,5-dimethylphenylcarbamate) coated onto a silica support, (d) CHIRALCEL OJ Cellulose tris (4-methylbenzoate) coated onto a silica support.

In a comparative study of 102 racemates of pharmaceutical interest with the three techniques, HPLC, CE, and SEC, HPLC was found to have the highest coverage of enantioseparation [64]. The authors state that this probably arose partly as a result of a higher variety of phases being commercially available for HPLC. The phases with the widest application ranges in that study were found to be Chiralpak AD and Chiralcel OD and OJ (i.e., polysaccharide phases). 

Lorazepam Chiralcel OD and Chiralpak AS n-Hexane-2-PrOH EtOH (5 5 1) Plasma nd [131]... 

As noted earlier, not all the prepared derivatives of cellulose and amylose are useful CSPs. Therefore, some of the useful derivatives of cellulose and amylose were selected and commercialized. The cellulose and amylose CSPs were commercialized by Daicel Chemical Industries of Tokyo. About 20 derivatives of cellulose and amylose are commercially available, as shown in Figure 8, with their chemical and trade names. The trade name of the cellulose and amylose derivatives are Chiralcel and Chiralpak, respectively. An R added to the end of a Chiralcel or Chiralpak trade name denotes a reversed-phase nature CSP. These CSPs are available in stainless steel columns of different dimensions and with different particle sizes. Generally the CSPs are available in the following range of column sizes and particle sizes (in parentheses) 25 cm x 0.46 cm... 

Gaffney [89] reported the reverse order of elution of 2-phenoxypropanoic acid on Chiralcel OB CSP when different alcohols were used. In 2001 Aboul-Enein and Ali [63] observed the reverse order of elution of nebivolol enantiomers on a Chiralpak AD chiral stationary phase when ethanol and 2-propanol were used separately as the mobile phases. However, the best resolution was obtained when ethanol served as the mobile phase. The inversion of the elution may be due to the different conformation of the polysaccharide CSPs [63]. The pattern of conversion of order of elution using different ratios of ethanol and 2-propanol is shown in Figure 15. 

Another study recorded the effect of the concentration of ammonium acetate on the chiral resolution of metomidate and etomidate on a Chiralpak AD-R column.. An increase in k values was observed with an increase in ammonium acetate concentration. On the other hand, the values of a decreased with an increase in ammonium acetate concentration [9]. The same trend was also observed on Chiralcel OD-R CSP for the chiral resolution of propranolol and trimepramine racemates [9]. 

FIGURE 16 Effects of acetonitrile percentage on the enantiomic resolution of (a) RS-2-(4-bromo-2-fluorobenzyl)-(l,2,3,4-tetrahydropyrrolo[l,2-a]pyrazine-4-spiro-3 -pyrrolidine)-l,2, 3,5 -tetrone on Chiralpak AD-RH and (b) Chiralcel OD-RH, and (c) flubiprofen on Chiralpak AD-RH CSP at different temperatures. (From Refs. 91, 92.)... 

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