Racemates chiral separation

A variety of strategies have been devised to obtain chiral separations. Although the focus of this article is on chromatographicaHy based chiral separations, other methods include crystallisation and stereospecific ensymatic-catalysed synthesis or degradation. In crystallisation methods, racemic chiral ions are typically resolved by the addition of an optically pure counterion, thus forming diastereomeric complexes. 

However, it was not until the beginning of 1994 that a rapid (<1.5 h) total resolution of two pairs of racemic amino acid derivatives with a CPC device was published [124]. The chiral selector was A-dodecanoyl-L-proline-3,5-dimethylanilide (1) and the system of solvents used was constituted by a mixture of heptane/ethyl acetate/methanol/water (3 1 3 1). Although the amounts of sample resolved were small (2 ml of a 10 inM solution of the amino acid derivatives), this separation demonstrated the feasibility and the potential of the technique for chiral separations. Thus, a number of publications appeared subsequently. Firstly, the same chiral selector was utilized for the resolution of 1 g of ( )-A-(3,5-dinitrobenzoyl)leucine with a modified system of solvents, where the substitution of water by an acidified solution... 

E. Erancotte, Chromatography as a separation tool for the preparative resolution of racemic compounds in Chiral separations, applications and technology, S. Ahuja (Ed.), American Chemical Society, Washington (1997) Chapter 10. 

If some fields may be empty in the sublevels, all the fields in the main level are required for each entry. A new chiral separation record can be added in CHIRBASE solely if the authors correctly identify both sample and CSP. Since the beginning of the project, our policy has been to contact the authors of all publications containing incomplete, ambiguous or inconsistent data and to ask for additional information. Providing the separations with unique case numbers helps us considerably in this essential task, and also facilitates avoiding redundancies in the database. When chiral separations are reported for the second time in a new publication with exactly the same chromatographic conditions, this is stated in a footnote added in the field comments . In this field, miscellaneous information that cannot appear elsewhere are listed (detection limit, description of a reported chromatogram, racemization study, mobile phase limitations, etc.). 

In general, a liquid membrane for chiral separation contains an enantiospecific carrier which selectively forms a complex with one of the enantiomers of a racemic mixture at the feed side, and transports it across the membrane, where it is released into the receptor phase (Fig. 5-1). 

Erancotte E. (1996) Chromatography as a Separation Tool for the Preparative Resolution of Racemic Compounds, in Chiral Separations. Applications and Technology, Ahuja S. (ed.), American Chemical Society, p. 271-308. 

Capillary electrophoresis employing chiral selectors has been shown to be a useful analytical method to separate enantiomers. Conventionally, instrumental chiral separations have been achieved by gas chromatography and by high performance liquid chromatography.127 In recent years, there has been considerable activity in the separation and characterization of racemic pharmaceuticals by high performance capillary electrophoresis, with particular interest paid to using this technique in modem pharmaceutical analytical laboratories.128 130 The most frequently used chiral selectors in CE are cyclodextrins, crown ethers, chiral surfactants, bile acids, and protein-filled... 

Kang, J. and Ou, Q., Chiral separation of racemic mexilitine hydrochloride using cyclodextrins as chiral additive by capillary electrophoresis,. Chromatogr. A, 795, 394, 1998. 

Chiral separation of the racemic product required silica gel separation of bis-camphanyl derivatives. 

FIGURE 14.2 Achiral-chiral separation of S-Ketorolac (S-l), R-Ketorolac (R-l), p-hydro-xyketorolac enantiomers (2,3) and internal standard Naproxen (4). (a) Urine blank (b) blank urine spiked with 1.5pg/mL each of racemic ketorolac and p-hydroxyketorolac (c) Nondeconjugated urine sample taken from a patient who received 10 mg of oral racemic ketorolac. Reprinted from Diaz-Perez et al. (1994) with permission from John Wiley Sons. 

In practise, if using one of these reagents to follow the course of a chiral separation, it is essential to determine whether resolution is possible, by performing a test experiment either on a sample of racemate, or at least a sample known to contain significant quantities of both enantiomers. Once useable resolution has been established, the technique can be used to monitor solutions of unknown enantiomer ratios with reasonable accuracy, down to normal NMR detection limits. 

The enantiomers of many compounds are eluted in reverse order on the 3,5-dimethylphenylcarbamates of cellulose (23x) and amylose (24n), suggesting that these two CSPs may be complementary in recognizing chirality. Many enantiomers unresolved on 23x can be resolved on 24n, and vice versa. Consequently, when two 23x and 24n columns were used for the resolution of 500 racemates, nearly 80% of the racemates were separated into enantiomers at least on either of 23x and 24n. 

Chiral chromatography Gas, liquid or supercritical fluid Chiral stationary phase (GC, LC and Racemates are separated into their... 

The development of chiral separation methods for dipeptides is of relevance for purity controls, for checking racemization processes in peptide syntheses, and for the investigation of peptide and protein hydrolysates. Since their introduction as chiral... 

Ding, GS. et ah. Chiral separation of racemates of drugs and amino acid derivatives by high-performance liquid chromatography on a norvancomycin-bonded chiral stationary phase, Chromatographia, 59, 443, 2004. 

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