Cyclodextrin stationary phase enantiomers

Elargitai, T., Kaida, Y., and Okamoto, Y., Preparation and chromatographic evaluation of 3,5-dimethylphenyl carbamoylated beta-cyclodextrin stationary phases for normal-phase high-performance liquid-chromatographic separation of enantiomers, J. Chromatogr., 628, 11, 1993. 

Yoshida, K. Nakagama, T. Uchiyama, K. and Hobo, T. (1998) Photo responsive chromatographic behavior of dansyl amino acid enantiomers using azobenzene-modified cyclodextrin stationary phases in... 

Juza, M, Braun, M., and Schurig, V. (1997) Preparative enantiomer separation of the chiral inhalation anesthetics enfiurane, isoflurane and desflurane by gas chromatography on a derivatized 7-cyclodextrin stationary phase, J. Chromatogr. A 769, 119-127. 

Schiirch, S., Saxer, A., Claude, S., Tabacchi, R., Trusch, B., and Hulliger, J. (2001) Semi-preparative gas chromatographic separation of ah-trans-perhydrotriphenylene enantiomers on a chiral cyclodextrin stationary phase, J. Chromatogr. A 905, 175-182. 

Jung and Schurig [7] have investigated enantiomeric separations using capillary SFC and an immobilized cyclodextrin stationary phase of film thickness 0.25 /tm. The authors found no loss in selectivity and column performance after several months. Many NSAID enantiomers could be separated, but amine-containing drugs such as ephedrine or synephrine had to be derivatized with trifluoroacetic acid anhydride prior to assay (see Fig. 

Enantiomeric analysis of a new antiinflammatory agent in rat plasma using a chiral p-cyclodextrin stationary phase" (71). The R,R S,S enantiomers of the investigational antiinflammatory agent trans-6,6a,7,10, 10a,ll-hexahydro-8,9-dimethyl-U-oxodibenz[b,e]-oxepin-3-acetic add (HOA) were resolved on the p-CD CSP after extraction from rat plasma. The mobUe phase was a mixture of 0.05 M potassium dihydrogenphosphate (pH 5.3) and methanol (35 65, v/v) the flow rate was 1.0 mL/min and the temperature was 22 1 C. The results of the study indicated that the inactive (—) enantiomer was cleared from the plasma more rapidly than the active (+) isomer. 

These stationary phases separate enantiomers on the basis that one isomer fits in the pocket and the other does not. In this fashion, the relative speed of the isomers is different, and separation results. There are three main types of inclusion chiral stationary phases a-cyclodextrin, /Tcyclodextrin, and y-cyclodextrin. From these three native cyclodextrins, several derivations can be made to alter the selectivity of the inclusion complex, including formation of acetates, esters, and carbamates. Astec produces all three native cyclodextrin stationary phases as well as several derivatized phases (called the Cyclobond series), and as with their macrolide polypeptide phases, they are covalently bonded. 

P.H. Kuijpers, T.K. Gerding and G.J. de Jong, Improvement of the Liquid Chromatographic Separation of the Enantiomers of Tetracyclic Eudistomins by the Combination of a P-cyclodextrin Stationary Phase and Camphor-sulphonic Acid as Mobile Phase Additive, J. Chromatogr., 625(1992) 223. 

The presence of asymmetric carbons in selenomethionine, other a-selenoamino acids, and related compounds produces different chiral enantiomers with different physiological activities. HPLC separation of enantiomers is possible with a range of chiral stationary phases, d- and 1-Selenomethionine enantiomers have been resolved with an a-cyclodextrin stationary phase and other species with a teicoplanin-based chiral phase. Hybrid chiral methodologies based on GC, HPLC, and capillary electrophoresis, coupled with ICP-MS are feasible. Enantiomers of d,l-selenocystine, d,l-selenomethio-nine, and d,l-selenoethionine were examined in a range of commercial dietary supplements using a chiral crown ether stationary phase and ICP-MS detection. Selenium-em-iched onion, garlic, and yeast were analyzed and some of the selenoamino acid enantiomers were identified. l-Fluoro-2, 4-dinitro-phenyl-5-l-alanine amide was used to derivatize enantiomers of selenoamides for enhanced resolution. 

Another type of stationary phase in gas chromatography is based on molecules such as the cyclodextrins. With these materials, the discrimination between enantiomers depends on the interactions between the stereoisomers and the chiral cavity that is formed within these materials. Because enantiomers differ in shape, they will fit differently within the chiral cavity. The result will be that the enantiomers will pass through the cyclodextrin stationary phase at different rates, thus leading to a separation. 

Enantiomeric mixtures of free sugars, e.g., DL-ribose or DL-arabinose, have been separated as their pertrifluoroacetylated derivatives by g.c. on di-O-pentyl- and (S)-hydroxypropyl-per-O-methyl-cyclodextrin stationary phases. Arabinitol enantiomers were similarly resolved as their pertrifluoroacetylated derivatives on pentylated cyclodextrin stationary phases.D-Arabinitol- H could then be used as the internal standard in the g.c.-m.s. analysis with selected ion monitoring of the D-isomer as an indicator of fungal infection by Candida species. ... 

A broad range of macrocyclic compounds can be used as chiral selectors for enantioselective HPLC. Besides synthetic crown ethers, derivatized cyclodextrins and cyclic antibiotics are also used as chiral stationary phases. Enantiomer separation employing these compounds is often based on host-guest interactions [15], whereby the cyclic molecules form an inclusion compound or an association complex with the analyte. 

A. M. Stalcup, Cyclodextrin bonded chiral stationary phases in enantiomer separations in A practical approach to chiral separations by liquid chromatogra.phy, G. Subramanian, VCH, Weinheim (1994) Chapter 5. 

There is a wide variety of commercially available chiral stationary phases and mobile phase additives.32 34 Preparative scale separations have been performed on the gram scale.32 Many stationary phases are based on chiral polymers such as cellulose or methacrylate, proteins such as human serum albumin or acid glycoprotein, Pirkle-type phases (often based on amino acids), or cyclodextrins. A typical application of a Pirkle phase column was the use of a N-(3,5-dinitrobenzyl)-a-amino phosphonate to synthesize several functionalized chiral stationary phases to separate enantiomers of... 

Lubda, D., Cabrera, K., Nakanishi, K., Lindner, W. (2003). Monolithic silica columns with chemically bonded b-cyclodextrin as a stationary phase for enantiomer separations of chiral pharmaceuticals. Anal. Bioanal. Chem. 377, 892-901. 

Pihlainen, K. and Kostiainen, R., Effect of the eluent on enantiomer separation of controlled drugs by liquid chromatography-ultraviolet absorbance detection-electrospray ionisation tandem mass spectrometry using vancomycin and native fi-cyclodextrin chiral stationary phases, J. Chromatogr. A, 1033, 91, 2004. 

Analysis using a CMPA is usually resolved on a nonchiral column. A transient diastereomeric complex is formed between the enantiomer and the chiral component in the mobile phase, similar to the complexes formed with chiral stationary phases. A review by Liu and Liu (2002) cites several papers where addition of CPMAs has been used in analyzing amphetamine-related compounds. Some CPMAs include amino acid enantiomers, metal ions, proteins, and cyclodextrins. Advantages of this method of analysis include the use of less expensive columns and more flexibility in the optimization of chiral separation (Misl anova and Hutta, 2003). 

A lot of published data on the separation of enantiomers of flavors and fragrances by GC is reviewed by Chirbase/Flavor database. Table 1. summarizes the enantiomer separation of oxygenated monoterpenes on chiral stationary phases of cyclodextrin derivatives by high resolution gas chromatography. 

Table 1. Enantiomer Separation of Oxygenated Monoterpenes on Chiral Stationary Phases of Cyclodextrin Derivatives by High Resolution Gas Chromatography...

---