Chiral stationary phases in HPLC

Kempe M. Antibody-mimicking polymers as chiral stationary phases in HPLC. Anal Chem 1996 68 1948-1953. 

H. Kaga, Precision synthesis of (1 —> 6)-o -D-glucopyranan by cationic ring-opening polymerization of l,6-anhydro-tri-0-allyl-/8-D-glucopyranose, Macromol. Symposia, 181 (2002) 101-106 (b) A. Kusuno, M. Mori, T. Satoh, M. Miura, H. Kaga, and T. Kakuchi, Enantioseparation properties of (1 - 6)- -i)-glucopyranan and (1 - 6)-a-D-mannopyranan tris(phenylcarbamate)s as chiral stationary phases in HPLC, Chirality, 14 (2002) 498-502. 

Ghanem, A., Aboul-Enein, H. Comparison, Applications, Advantages, and Limitations of Immobilized and Coated Amylose Tris-(3,5-Dimethylphenylcarbamate) Chiral Stationary Phases in HPLC,/. Liq. Chromatogr. Relat. Technol., 2005, 28, 2863-2874. 

CD-bonded stationary phases are suitable for the separation of positional, geometric and optical isomers, derivatives of dansyl racemic amino acids, analogues of nicotine and nicotine analogs, arbitrates and derivatives of benzodiazepin as well as organic nitrates, imidazol derivatives, etc. Table 8.2 shows that some enantioselective stationary phases are based on modified CDs [32,33]. The first CD derivatives used as a chiral stationary phase in HPLC were hydroxypropyl, acetylated and carbamoylated /3-CD, which demonstrated better selectivity behaviors than native /3-CD. The most common commercial species of CD derivatives include water-soluble methylated CD (2,6-di-0-methyl-j8-CD) and HP-j6-CD, then acetylated CD, carboxymethylated CD, naphthyl ethyl carbamate-j8-CD,... 

In addition to the development of the powerful chiral additive, this study also demonstrated that the often tedious deconvolution process can be accelerated using HPLC separation. As a result, only 15 libraries had to be synthesized instead of 64 libraries that would be required for the full-scale deconvolution. A somewhat similar approach also involving HPLC fractionations has recently been demonstrated by Griffey for the deconvolution of libraries screened for biological activity [76]. Although demonstrated only for CE, the cyclic hexapeptides might also be useful selectors for the preparation of chiral stationary phases for HPLC. However, this would require the development of non-trivial additional chemistry to appropriately link the peptide to a porous solid support. 

Our efforts to concretely determine the relative stereochemistry of this dimer have been met by failure. We have made attempts to resolve several of the monomeric tetracyclic aminoaldehydes of type 100 by HPLC using chiral stationary phase, in order to know for sure the structure of the homodimer. The poor solubility of these compounds in typical HPLC solvents hampered these efforts to access enantiopure monomer. A few attempts at diastereomeric salt formation from compounds of type 101 using chiral carboxylic acids were also unsuccessful. Computational analysis corroborates the assumption that the homodimer should be formed preferentially. 

D Acquarica, L, New synthetic strategies for the preparation of novel chiral stationary phases for HPLC containing natural pool selectors, presented at 8 Int. Meeting on Recent Developments in Pharmaceutical Analysis, Roma, June 29-July 3, 1999, 37. 

Brain K, Rao KRN, Lloyd MJB, Novel chiral stationary phases, in Chiral Separations by HPLC, Krstulovic AM (Ed.), Ellis Horwood, Chichester (1989). 

To establish chiral separation method for donepezil hydrochloride enantiomers by capillary electrophoresis (CE) and to determine the two enantiomers in plasma [39], alkalized plasma was extracted by isopropa-nol-n-hexane (3 97) and L-butefeina was used as the IS. Enantioresolution was achieved using 2.5% sulfated-beta-cyclodextrin as chiral selector in 25 mmol/1 triethylammonium phosphate solution (pH 2.5) on the uncoated fused-silica capillary column (70 cm x 50 fim i.d.). The feasibility of the method to be used as quantitation of donepezil HC1 enantiomers in rabbit plasma was also investigated. Donepezil HC1 enantiomers were separated at a baseline level under the above condition. The linearity of the response was evaluated in the concentration range from 0.1 to 5 mg/1. The linear regression analysis obtained by plotting the peak area ratio (A(s)/A(i)) of the analyte to the IS versus the concentration (C) showed excellent correlation coefficient The low limit of detection was 0.05 mg/1. The inter- and intra-day precisions (RSD) were all less than 20%. Compared with chiral stationary phase by HPLC, the CE method is simple, reliable, inexpensive, and suitable for studying the stereoseletive pharmacokinetics in rabbit. 

Chirality of derivatized cyclodextrin was used for recognition of stereoisomers. Phenylazobenzoyl modified y-cyclodextrin was anchored onto silica gel used as stationary phase in HPLC and photoresponsive chromatographic behavior of dansyl amino acid enantiomers was studied [64],... 

Another way to obtain pure enantiomers is the separation of racemates through preparative chromatography on chiral stationary phases. In fact, the most significant developments over the last 20 years have been the application of GLC and HPLC techniques to the effective resolution of enantiomeric mixtures and to determining the enantiomeric ratio [7,8],... 

The thermodynamic and hydrogen-bond basicity of 1 have been reported by the group of Berthelot, Laurence and coworkers (04CJC1413). TB 1, TB 110 and another mixed crown ether TB have been reported in a communication dealing with a novel chiral stationary phase for HPLC (94JCS(CC)1811). 

---