Enantiomers chiral chromatography

Chromatography may be used for the direct separation of enantiomers ( chiral chromatography ) and also for the normal separation of diastereomeric pairs. 

Chiral Chromatography. Chiral chromatography is used for the analysis of enantiomers, most useful for separations of pharmaceuticals and biochemical compounds (see Biopolymers, analytical techniques). There are several types of chiral stationary phases those that use attractive interactions, metal ligands, inclusion complexes, and protein complexes. The separation of optical isomers has important ramifications, especially in biochemistry and pharmaceutical chemistry, where one form of a compound may be bioactive and the other inactive, inhibitory, or toxic. 

The past two decades have seen remarkable advances in chiral chromatography, as only 20 years ago, the direct resolution of enantiomers by chromatography was still considered to be an impressive technical achievement. 

Volume inefficient chiral chromatography required to deliver a single enantiomer Separation at final API necessitated processing excess material through the synthesis to give the desired amount... 

Volume inefficient chiral chromatography required to deliver a single enantiomer... 

Kim, K.H., Kim, H.J., Kang, J.-S., Mar, W. (2000b). Determination of metoprolol enantiomers in humanurineby coupled achiral-chiral chromatography. J. Pharm. Biomed. Anal. 22,377-384. 

In principle, mass spectrometry is not suitable to differentiate enantiomers. However, mass spectrometry is able to distinguish between diastereomers and has been applied to stereochemical problems in different areas of chemistry. In the field of chiral cluster chemistry, mass spectrometry, sometimes in combination with chiral chromatography, has been extensively applied to studies of proton- and metal-bound clusters, self-recognition processes, cyclodextrin and crown ethers inclusion complexes, carbohydrate complexes, and others. Several excellent reviews on this topic are nowadays available. A survey of the most relevant examples will be given in this section. Most of the studies was based on ion abundance analysis, often coupled with MIKE and CID ion fragmentation on MS " and FT-ICR mass spectrometric instruments, using Cl, MALDI, FAB, and ESI, and atmospheric pressure ionization (API) methods. 

As discussed earlier, the concepts of chiral chromatography can be divided into two groups, the indirect and the direct mode. The indirect technique is based on the formation of covalently bonded diastereomers using an optically pure chiral derivatizing agent (CDA) and reacting it with the pair of enantiomers of the chiral analyte. The method of direct enantioseparation relies on the formation of reversible quasi diastereomeric transient molecule associates between the chiral selector, e.g., i /t)-SO, and the enantiomers of the chiral selectands, [R,S)-SAs [(Ry SA + (S)-SA] (Scheme 1). 

Among the recent instrumental methods, chiral chromatography can be used to separate enantiomers. The most commonly used chromatographic technique is chiral high performance liquid chromatography (HPLC). 

Diastereomeric interaction between molecules of the racemic mixture and the chiral chromatography medium causes enantiomers of the racemate to move through the stationary phase at different rates. 

Separations of enantiomers can be achieved by chiral chromatography. Even, when the enantioselective synthesis of drugs and pharmaceuticals is possible, a major part of chiral compounds is still produced as a racemate and needs to be separated into the enantiomers by chiral high performance liquid chromatography. 

Biopolymers in Chiral Chromatography. Biopolymers have had a tremendous impact on the separation of nonsupernnposable. mirror-image isomers known as enantiomers. Enantiomers have identical physical and chemical properties in an achiral environment except that they rotate the plane of polarized light in opposite directions. Thus separation of enantiomers by chromatographic techniques presents special problems. Direct chiral resolution by liquid chromatography (lc) involves diastereomenc interactions between the chiral solute and the chiral stationary phase. Because biopolymers are chiral molecules and can form diastereomeric... 

In contrast, CSPs have achieved great repute in the chiral separation of enantiomers by chromatography and, today, are the tools of the choice of almost all analytical, biochemical, pharmaceutical, and pharmacological institutions and industries. The most important and useful CSPs are available in the form of open and tubular columns. However, some chiral capillaries and thin layer plates are also available for use in capillary electrophoresis and thin-layer chromatography. The chiral columns and capillaries are packed with several chiral selectors such as polysaccharides, cyclodextrins, antibiotics, Pirkle type, ligand exchangers, and crown ethers. 

M. Yamaguchi, K. Yamashita, I. Aoki, T. Tabata, S.-I. Hirai and T. Yashiki, Determination of manidipine enantiomers in human serum using chiral chromatography and column-switching liquid chromatography , 7. Chromatogr. 575 123-129 (1992). 

Note here that for (semi)industrial scale production, both enantiomers were obtained starting from the racemic mixture by preparative chiral chromatography. 

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