Amylose-based phase

The most successful and broadly applied chiral stationary phases comprise the cellu-lose-and amylose-based phases developed by Okamoto (Chiracel and Chiralpak) (39), brush-type phases developed by Pirkle (40),... 

From the list in Table 3.9, cellulose and amylose-based phases are by far the most often used in preparative and, especially, SMB applications. These adsorbents offer good productivities because of their high loadabilities (Fig. 3.22). In addition, the four most commonly used CSP of this type separate a broad range of different race-mates. The major problem of these adsorbents is their limited solvent stability, especially towards medium-polar solvents such as acetone, ethyl acetate or dioxane. In the past their use in conjunction with aqueous mobile phases was not recommended by the manufacturer as well. However, this limitation was successfully overcome by recent studies, in which amylose- and cellulose-based CSPs are transferred to the reversed phase (RP) mode with aqueous mobile phases. The first results for the use of polysaccharide-type phases with aqueous solvents were reported by Ishikawa and Shibata (1993) and McCarthy (1994). The stability of the adsorbent after switching to RP conditions has been reported by Kummer et al. (1996) to be at least 11 months and by Ning (1998) to be 3 years. No peak deviation is observed after switching to RP mode. Novel developments have led to polysaccharide-based adsorbents dedicated to use with nearly all organic solvents (Cox and Amoss, 2004). 

In sub-FC, a detailed study of the influence of mobile phase additives on the chiral resolution of isoxazoline-based Ilb/IIIb receptor antagonists was carried out by Blackwell [145] on Chiralcel OD-H CSPs. The different mobile phase additives used were acetic acid, trifluoroacetic acid, formic acid, water, triethylamine, triethanolamine, n-hexylamine, trimethyl phosphate, and tri-w-butyl phosphate. In general, n-hexylamine and tri-/ -butyl phosphate mobile phase additives resulted in better resolution. The chiral separation of four 1,3-dioxolane derivatives on an amylose-based column has been described [151]. The effects of mobile phase composition, temperature, and pressure have been investigated. The nature of the modifier is the main parameter it has the highest impact on chiral resolution and is more important than the polarity of the mobile phase. Therefore, the organic modifier that gave the best enantiomeric separation was different for each compound. 

Balmer et al. [60] separated the two enantiomers of omeprazole on three different stationary phases with immobilized protein, viz, Chiral-AGP with a-1 acid glycoprotein, Ultron ES-OVM with ovomucoid, and BSA-DSC with BSA cross-linked into 3-aminopropyl silica using N-suc-cinimidyl carbonate. The mobile phase (1 ml/min) was phosphate buffer solution with 3—10% 2-propanol as the organic modifier. The enantiomers of omeprazole were separated on Chiralpak AD, an amylose-based chiral stationary phase, with ethanol-hexane (1 4) as mobile phase (1 ml/min). 

Yamamoto, C., Hayashi, T., Okamoto, Y., Ohkubo, S., and Kato, T. (2001) Direct resolution of CK enantiomers by HPLC using an amylose-based chiral stationary phase, Chem. Commun. 925-926. 

The enantiomers of pantoprazole were also separated by Balmer et al using a chiral stationary phase [12]. The method is based on using a mixture of ethanol and hexane (1 4 v/v) as mobile phase, eluted at 1 mL/min, and Chiralpak AD (an amylose-based chiral material) as the stationary phase. 

Advances in preparative enantioseparation by simulated moving bed (SMB) chromatography have occurred in the last 10 years. SMB was invented in the 1960s and was used by the petrochemical and sugar industries. Now with the improvements in stationary phases and hardware it is an option for the large-scale preparation of enantiomerically pure material. The majority of the latest published data are using either amylose- or cellulose-based phases because of their selectivity. There are now examples in the literature of the commercial separation on the multi-ton scale.8... 

The Protein Phases The Pirkle Stationary Phases The Cellulose and Amylose Stationary Phases The Macrocyclic Glycopeptide Stationary Phases The Cyclodextrin Based Stationary Phases Appendix Index... 

The most effective cellulose and amylose based chiral stationary phases are those derivatized with the various substituted tris(3,5-dimethylphenyl carbamates). Okamoto et al. [10], carried out an extensive study on the effect of the different substituent groups on the chiral selectivity of the stationary phase to a range of protected amino acid derivatives. An example of one of their separations is given in figure 11.12. 

The cellulose and amylose based stationary phases are more often effectively used in normal phase mode. The carbamates, however, are claimed to function in high concentrations of water, and have been used successfully with a mobile phase of pure buffer. There are three basic... 

The Preparation of the Pirkle Stationary Phases The Preparation of Cellulose and Amylose Stationary Phases The Preparation of the Macrocyclic Glycopeptides Phases The Preparation of the Cyclodextrin Based Stationary Phases Column Packing Techniques... 

Booth TD, Lough WJ, Saeed M, Noctor TAG, Wainer IW (1997) Enantioselective separation of enantiomeric amides on three amylose-based chiral stationary phases effects of backbone and carbamate side chain chiralities. Chirality 9 173-177... 

Aboul-Enein, H.Y. Ali, I. HPLC enantiomeric resolution of nebivolol on normal and reversed amylose based chiral phases, Pharmazie, 2001, 56, 214-216. 

The most popular CSPs selected to be included in the reported chiral column screening schemes are four polysaccharide-based phases, including cellulose tris(3,5-dimethylphenylcarbamate), cellulose tris-4-methylbenzoate, amylose... 

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... 

Cellulose and amylose derivative CSPs are mostly used, in the normal-phase mode, with n-hexane-based mobile phases containing some alcohol as modifier. Chromatographic performances, retention and selectivity, are reported to be affected by the composition of the mobile phase... 

Cass et al. [66] used a polysaccharide-based column on multimodal elution for the separation of the enantiomers of omeprazole in human plasma. Amylose tris (3,5-dimethylphenylcarbamate) coated onto APS-Hypersil (5 /im particle size and 120 A pore size) was used under normal, reversed-phase, and polar-organic conditions for the enantioseparation of six racemates of different classes. The chiral stationary phase was not altered when going from one mobile phase to another. All compounds were enantioresolved within the elution modes with excellent selectivity factor. The separation of the enantiomers of omeprazole in human plasma in the polar-organic mode of elution is described. 

The majority of preparative separations undertaken at Ultrafine have used chiral stationary phases based on either cellulose or amylose derivatives. In one project 500 mg of salts of both the (R,R)- and (S,S)-Formoterol (6) enantiomers were prepared using an OJ column with a resulting ee of >97%.45 A loading of 200 mg/mL on a semipreparative column was achievable without loss of resolution or purity relative to the racemate. 

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