Chiral stationary phases chromatography

Complexation with Chiral Metal Complexes. This idea was first suggested by Feibush et al.44 The separation is realized by the dynamic formation of diastereomeric complexes between gaseous chiral molecules and the chiral stationary phase in the coordination sphere of metal complexes. A few typical examples of metal complexes used in chiral stationary phase chromatography are presented in Figure 1-13.45... 

Oxazine 115 with a 2-hemiacetal racemizes in ethyl acetate solution at above 50 °C but the racemic mixture can be resolved by chiral stationary phase chromatography <2005W040140>, or crystallization using (-)-(/ ,iJ)-di- -toluoyl-tartaric acid (DTTA) <2005W040141> as shown in Scheme 2. 

Thin-Layer Chromatography. Chiral stationary phases have been used less extensively in tic as in high performance Hquid chromatography (hplc). This may, in large part, be due to lack of avakabiHty. The cost of many chiral selectors, as well as the accessibiHty and success of chiral additives, may have inhibited widespread commerciali2ation. Usually, nondestmctive visuali2ation of the sample spots in tic is accompHshed using iodine vapor, uv or fluorescence. However, the presence of the chiral selector in the stationary phase can mask the analyte and interfere with detection (43). 

Diamide Chiral Separations. The first chiral stationary phase for gas chromatography was reported by GH-Av and co-workers in 1966 (113) and was based on A/-trifluoroacetyl (A/-TFA) L-isoleucine lauryl ester coated on an inert packing material. It was used to resolve the tritiuoroacetylated derivatives of amino acids. Related chiral selectors used by other workers included -dodecanoyl-L-valine-/-butylamide and... 

Gas chromatography (gc) is inferior to hplc in separating abiUty. With gc, it is better to use capillary columns and the appHcation is then limited to analysis (67). Resolution by thin layer chromatography or dc is similar to Ic, and chiral stationary phases developed for Ic can be used. However, tic has not been studied as extensively as Ic and gc. Chiral plates for analysis and preparation of micro quantities have been developed (68). 

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. 

Synthetic chiral adsorbents are usually prepared by tethering a chiral molecule to a silica surface. The attachment to the silica is through alkylsiloxy bonds. A study which demonstrates the technique reports the resolution of a number of aromatic compoimds on a 1- to 8-g scale. The adsorbent is a silica that has been derivatized with a chiral reagent. Specifically, hydroxyl groups on the silica surface are covalently boimd to a derivative of f -phenylglycine. A medium-pressure chromatography apparatus is used. The racemic mixture is passed through the column, and, when resolution is successful, the separated enantiomers are isolated as completely resolved fiactions. Scheme 2.5 shows some other examples of chiral stationary phases. 

HPLC separations are one of the most important fields in the preparative resolution of enantiomers. The instrumentation improvements and the increasing choice of commercially available chiral stationary phases (CSPs) are some of the main reasons for the present significance of chromatographic resolutions at large-scale by HPLC. Proof of this interest can be seen in several reviews, and many chapters have in the past few years dealt with preparative applications of HPLC in the resolution of chiral compounds [19-23]. However, liquid chromatography has the attribute of being a batch technique and therefore is not totally convenient for production-scale, where continuous techniques are preferred by far. 

W. H. Pirkle and B. C. Hamper, The direct preparative resolution of enantiomers by liquid chromatography on chiral stationary phases in Preparative Liquid Chromatography, B. A. Bidling-meyer (Ed.), Journal Chromatography Library Vol. 38, 3 Edition, Elsevier Science Publishers B. V, Amsterdam (1991) Chapter 7. 

Despite the difficulties caused by the rapidly expanding literature, the use of chiral stationary phases (CSPs) as the method of choice for analysis or preparation of enantiomers is today well established and has become almost routine. It results from the development of chiral chromatographic methods that more than 1000 chiral stationary phases exemplified by several thousands of enantiomer separations have been described for high-performance liquid chromatography (HPLC). 

The versatility of chiral stationary phases and its effecitve application in both analytical and large-scale enantioseparation has been discussed in the earlier book A Practical Approach to Chiral Separation by Liquid Chromatography" (Ed. G. Sub-ramanian, VCH 1994). This book aims to bring to the forefront the current development and sucessful application chiral separation techniques, thereby providing an insight to researchers, analytical and industrial chemists, allowing a choice of methodology from the entire spectrum of available techniques. 

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