Chiyo Yamamoto

Enantioseparation of selected chiral sulfoxides using polysaccharide-type chiral stationary phases and polar organic, polar aqueous-organic and normal-phase eluents.

HPLC enantioseparation of selected chiral sulfoxides was studied using cellulose and amylose phenylcarbamate derivatives as chiral stationary phases (CSPs). The contributions of various functional groups of a chiral analyte as well as the polysaccharide derivatives in the analyte retention and chiral recognition were evaluated. A very high enantioseparation factor exceeding 110 was observed in the enantioseparation of 2-(benzylsulfinyl)benzamide (BSBA) on cellulose tris(3,5-dichlorophenylcarbamate) (CDCPC) CSP by using 2-propanol as a mobile phase. The enantiomer elution order was opposite on cellulose and amylose phenylcarbamates. For the polysaccharide-type CSPs, pure alcohols such as methanol, ethanol and 2-propanol represent a valuable alternative to more common alcohol-hydrocarbon and reversed-phase eluents.

Comparative enantioseparation of selected chiral drugs on four different polysaccharide-type chiral stationary phases using polar organic mobile phases

The enantiomers of randomly selected chiral drugs and drug analogs of various structural and pharmacological groups were resolved on four different polysaccharide-type chiral stationary phases (CSP) using pure methanol and acetonitrile as mobile phases. Polysaccharide phenylester type CSP, Chiralcel-OJ although resolving the enantiomers of some chiral drugs was less universal in the combination with methanol and acetonitrile as mobile phases. Among polysaccharide phenylcarabamates amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak-AD) was superior over the corresponding cellulose derivative, cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel-OD). However, another derivative of cellulose, namely, cellulose tris(3,5-dichlorophenylcarbamate) (CDCPC) exhibited higher chiral recognition ability compared to Chiralpak-AD material. This study confirms previous findings about the applicability of polysaccharide type CSPs in so called polar organic mode as well as shows high potential of CDCPC as a practically useful CSP for High performance liquid chromatography (HPLC) enantioseparations.

Polysaccharide derivatives as useful chiral stationary phases in high-performance liquid chromatography

The chromatographic separation of enantiomers using chiral stationary phases (CSPs) has significantly advanced. The esters and carbamates of polysaccharides coated on silica gel have been extensively studied and widely used as CSPs for high-performance liquid chromatography (HPLC). In order to overcome the strict solvent limitation on these coated CSPs, the preparation of a new generation of CSPs consisting of immobilized polysaccharide derivatives has become increasingly important. The universal solvent compatibility of the new CSPs provides flexibility in both analytical and preparative chromatographies.

Immobilized-type chiral packing materials for HPLC based on polysaccharide derivatives

The polysaccharide-based chiral packing materials (CPMs) for high-performance liquid chromatography (HPLC) have been recognized as the most powerful ones for the analyzing and preparative separating of the chiral compounds. These CPMs have been conventionally prepared by coating polysaccharide derivatives on a silica gel support. This means that the solvents, which swell or dissolve the derivatives on the silica gel and reduce the performance of the chiral columns, do not allow to be applied as components of the eluents. Therefore, the polysaccharide-based CPMs can be used with a rather limited number of eluents. In order to enhance the versatility of the eluent selection for more practical and economical chromatographic enantioseparations, the polysaccharide derivatives must be immobilized onto the silica gel. This review summarizes our latest studies on the development of the immobilized-type CPMs via the radical copolymerization and the polycondensation of the polysaccharide derivatives bearing small amounts of vinyl groups and alkoxysilyl groups, respectively.

Comparative study on the application of capillary liquid chromatography and capillary electrochromatography for investigation of enantiomeric purity of the contraceptive drug levonorgestrel.

In the last few years, it has been shown that capillary electrochromatography (CEC) is a promising technique for enantioseparations. However, to date almost no studies are published on a critical comparison of CEC and its pressure-driven counterpart, capillary liquid chromatography (CLC) for real samples. In this study, the goal was to compare CLC and CEC for the determination of the enantiomeric purity of the contraceptive drug levonorgestrel and its pharmaceutical formulation. The study prevailed that not all potential advantages of CEC over CLC can easily be transformed in a real gain of detection limit of the enantiomeric impurity. However, certain advantages of CEC over CLC have been unambiguously shown.

Enantioseparations in nonaqueous capillary liquid chromatography and capillary electrochromatography using cellulose tris(3,5-dimethylphenylcarbamate) as chiral stationary phase

The potential of the widely used chiral stationary phase for high‐performance liquid chromatography (HPLC) enantioseparations, cellulose tris(3,5‐dimethylphenylcarbamate) (CDMPC, sold under the trade name Chiralcel OD) was evaluated under the conditions of nonaqueous capillary electrochromatography (CEC). The effect of the particle size of the silica gel, the loading of CDMPC on the silica gel and nature of the organic solvent, as well as electrolyte salts on the separation characteristics were investigated. This study illustrates the applicability of CDMPC for obtaining highly efficient enantioseparations under the conditions of nonaqueous CEC. Comparative study of enantioseparations in capillary liquid chromatography (CLC) and CEC indicated the significant advantages of CEC such as higher plate number at the similar linear flow rates of the mobile phase as well as better tolerance of higher linear flow rates.

Enantioseparations Using Cellulose Tris(3,5-dichlorophenylcarbamate) During High-performance Liquid Chromatography with Analytical and Capillary Columns: Potential for Screening of Chiral Compounds

The appropriate selection of the mobile phase facilitated the use cellulose tris(3,5-dichlorophenylcarbamate (CDCPC) as a chiral stationary phase (CSP) during high-performance liquid chromatography (HPLC). A preliminary evaluations of this material indicated its very high chiral resolving ability toward many analytes of different chemical and pharmacological groups. Some chemicals and drugs containing two centers of chirality were also successfully resolved into all possible stereoisomers. The applicability of CDCPC for enantioseparations in capillary liquid chromatography was also shown giving promising prospects for the screening of novel biologically active compounds (which may be also synthesized based on combinatorial strategies) for their enantiomeric composition.

Organic-Inorganic Hybrid Materials for Efficient Enantioseparation Using Cellulose 3,5-Dimethylphenylcarbamate and Tetraethyl Orthosilicate

The hybrid bead-type chiral packing material (CPM) for preparative enantioseparation has been prepared from the cellulose 3,5-dimethylphenylcarbamate containing a small number of 3-(triethoxysilyl)propyl groups in the presence of tetraethyl orthosilicate, by a sol-gel reaction in an aqueous surfactant solution. The obtained hybrid bead-type CPM was packed into a column and evaluated by high-performance liquid chromatography. When compared with the commercially available Chiralpak IB, which is prepared by the immobilization of cellulose 3,5-dimethylphenylcarbamate on silica gel, the hybrid bead-type CPM was shown to exhibit a similar chiral recognition and possess a higher loading capacity.

Enantioseparation using ortho- or meta-substituted phenylcarbamates of amylose as chiral stationary phases for high-performance liquid chromatography.

Six ortho- and six meta-substituted phenylcarbamate derivatives of amylose were prepared and their chiral recognition abilities were evaluated as chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC). The substitution at the meta-position on the aromatic ring was more preferable than that at the ortho-position to obtain CSPs with a high chiral recognition ability, and the introduction of either an electron-withdrawing or electron-donating substituent can improve the chiral resolving power of the meta-substituted phenylcarbamates of amylose. The chiral recognition ability of the amylose phenylcarbamates and elution order of the enantiomers were significantly dependent on the position, nature and number of the substituents on the phenyl group. Correlations between the chiral recognition ability and the N-H frequencies in the IR spectra and the chemical shifts of the N-H protons in the (1)H NMR spectra of the carbamate moieties of the amylose derivatives were discussed. The structures of the amylose derivatives were also investigated by circular dichroism spectroscopy.

Chiral recognition of cellulose tris(5-fluoro-2-methylphenylcarbamate) toward (R)- and (S)-1,1′-bi-2-naphthol detected by electron ionization mass spectrometry

A new method for the detection of chiral recognition was developed through a mass spectrometric study of the desorption of a chiral guest compound (analyte) from a chiral host compound (adsorbent). Optically active cellulose tris(5-fluoro-2-methylphenylcarbamate) (1) was used as the chiral adsorbent, which has been synthesized and used as a chiral stationary phase (CSP) in high-performance liquid chromatography (HPLC). As the chiral analytes, (R)- and (S)-1,1′-bi-2-naphthol (2) were selected. The phenylcarbamate derivative shows high chiral resolving ability in HPLC and completely resolves the enantiomers of 2 with high selectivity; the (R)-enantiomer elutes first, followed by the (S)-enantiomer. A mixture of (RS)-2 and 1 was ionized by electron ionization using a direct insertion probe operated by temperature programming at 32 °C min–1 from 25 to 400 °C. Reconstructed ion current profiles of (R)- and (S)-2 showed different shapes, which may result from their different adsorption and/or desorption from the chiral adsorbent (1). The chiral discrimination in MS was confirmed using partially deuterated 2 and was quite consistent with the HPLC enantioseparation results using 1 as a CSP.