High-performance liquid chromatographic enantioseparation of N-protected α-amino acids using nonporous silica modified by a quinine carbamate as chiral stationary phase

In this study, tert-butyl carbamoylated quinine as chiral selector was immobilized on nonporous silica (NPS) 1.5 μm particles developed by MICRA, and this new chiral stationary phase (CSP) was packed into a 3.3 cm column (4.6 mm ID). A series of various N-protected α-amino acids was chosen as chiral selectands, including 3.5-dinitrobenzyloxycarbonyl amino acids (DNZ-AAs). In order to optimize the chromatographic conditions with this novel CSP and to apply it to the resolution of acidic analytes the following parameters have been varied and studied: pH of the mobile phase, buffer concentration, and percentage of methanol or acetonitrile in the mobile phase. DryLab^R software was applied to optimize enantioseparation by simulating chromatographic functions of experimental conditions for isocratic and/or gradient runs. Thus, we were able to resolve a set of test compounds within several minutes, whereby our attention was particularly drawn to the resolution of DNZ-AA derivatives. Chirality 9:157–161, 1997. © 1997 Wiley-Liss, Inc.     

Polymer-supported chiral diol as ligand of Ti(IV) for enantioselective Diels-Alder reaction

The synthesis of the first polymer-supported TADDOL is reported. Its efficiency as chiral ligand of Ti(IV) was studied in the Diels-Alder cycloaddition of cyclopentadiene to 3-crotonoyl-1,3-oxazolidin-2-one, and was superior to that observed for its homogeneous equivalent. (4R,5R)-α,α,α′,α′-2-pentaphenyl-4,5-dimethanol-1,3-dioxolane. Recycling of the heterogeneous Ti(IV)-TADDOLate was also studied, being the most suitable method for the repreparation of the catalyst from the ligand after use. Chirality 9:191–197, 1997. © 1997 Wiley-Liss, Inc.     

Enantiomeric separation of amino alcohols using Z-L-glu-L-pro or Z-L-glu-D-pro as chiral counter ions and hypercarb as the solid phase

This paper describes the synthesis of two new N-derivatized dipeptides. The two compounds, N-benzyloxycarbonyl-L-glutamyl-L-proline (Z-L-glu-L-pro) and N-benzyloxycarbonyl-L-glutamyl-D-proline (Z-L-glu-D-pro), were tested as chiral counter ions for the enantiomeric resolution of amino alcohols. The chiral counter ions were dissolved in a polar solvent, e.g., methanol and porous graphitic carbon, Hypercarb, were used as the achiral solid phase. The enantiomers of several of the tested compounds were baseline separated using Z-L-glu-L-pro as the chiral counter ion but no enantioselective retention was obtained using its diastereoisomer Z-L-glu-D-pro. The influence of solute structure as well as the importance of converting the chiral counter ion to its dianionic form will be described together with the effect of column temperature on enantioselective retention. Chirality 9:650–655, 1997. © 1997 Wiley-Liss, Inc.     

Chiral resolution and absolute configuration of the enantiomers of 5-acetyl-2-methyl-4-methylsulfinyl-6-phenyl-3(2H)-pyridazinone and evaluation of their platelet aggregation inhibitory activity

In a series of 5-acyl-6-phenyl-2,4-substituted-3(2H)-pyridazinones the derivative 1a , with a sulfur stereogenic center, had the most potent activity as human platelet aggregation inhibitor. The resolution of rac- 1a was successfully performed by chiral chromatography on Chiralcel OD-R, OD-H, and Chiralpak AD columns and scaled up to a preparative level. The absolute configuration of (−)-(S)- 1a was determined by X-ray crystallographic analysis. In vitro human platelet aggregation inhibitory activity was evaluated. Both the enantiomers showed IC₅₀ values in the same micromolar range, but the (−)-(S) isomer was slightly more potent [(S)/(R) potency ratio was 4/1]. Chirality 9:681–685, 1997. © 1997 Wiley-Liss, Inc.     

Temperature effects for chiral separations using various bulk fluids in near-critical mobile phases

As supercritical fluid chromatography becomes more accepted as a facile means for the separation of chiral compounds, the need for mobile phases that can readily solubilize these polar compounds grows. Prior studies suggest that HFC-134a may prove suitable due to its very high eluotropic strength compared to carbon dioxide-based mobile phases. A comparison is made between ethanol-modified carbon dioxide, HFC-134a, and decafluoropentane as to their relative eluotropic strength, selectivity, and efficiency for three chiral compounds using a Whelk O-1 chiral bonded phase. The bulk component of the mobile phase was found to have relatively little effect on chiral selectivity over the range of 5° to 95°C. Chirality 9:693–698, 1997. © 1997 Wiley-Liss, Inc.     

Enantiomeric separation of some piperidine-2,6-dione drugs using chiralcel OJ-R column

A newly developed reversed phase cellulose tris(4-methyl benzoate) known as Chiralcel OJ-R was used to investigate the chiral recognition and enantiomeric separation of eight racemic piperidine-2,6-dione compounds—namely, aminoglutethimide and its major metabolite acetylaminoglutethimide, glutethimide, cyclohexylamino-glutethimide, pyridoglutethimide, thalidomide, phenglutarimide, and 3-phenylacetyl-amino-2,6-piperidinedione (antineoplaston A-10). Chiral separation of these compounds was achieved under varying ratios of the mobile phase, except for phenglutarimide and 3-phenylacetylamino-2,6-piperidinedione, for which separation was unsuccessful. Possible chiral recognition mechanisms are also presented. Chirality 9:10–12, 1997. © 1997 Wiley-Liss, Inc.     

Chiral discrimination using a quartz crystal microbalance and comparison with gas chromatographic retention data

Quartz crystal microbalances (QCMB) have been constructed using 10 MHz AT cut quartz crystals coated with heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, heptakis(6-O-methyl-2,3-di-O-pentyl)-β-cyclodextrin, and octakis(6-O-methyl-2,3-di-O-pentyl)-γ-cyclodextrin as 50% and 20% (w/w) solutions in OV1701. The reduction in frequency seen on exposure of each coated QCMB to pure enantiomeric forms of α- and β-pinene and cis- and trans-pinane show that statistically significant (P = 0.05, n = 7) differences are observed between the enantiomeric pairs. The apparent preferential binding shown by the QCMB for enanciomers of α- and β-pinene and cis- and trans-pinane have been compared with the elution order observed on the corresponding gas chromatographic stationary phase. The magnitude of the observed separation factor (calculated as the ratio of the OV1701 normalised frequency shift) is seen to be dependent upon the chiral stationary phase concentration. These results indicate that on-line determination of enantiomeric excess and concentration of certain monoterpenes is possible at room temperature using QCMB in conjunction with chiral gas chromatographic stationary phases. Chirality 9:225–232, 1997. © 1997 Wiley-Liss, Inc.     

Improvement of enantioselective syntheses and chiral high resolution gas chromatographic analyses of (+)-2-allyl-2-carboethoxy-cyclopentanol

The improvement of the biocatalytic reduction of 2-allyl-carboethoxy-cyclopentanone (2) to the corresponding cyclopentanol derivative (+)-(1R,2R)-(1) was accomplished employing baker's yeast in organic media. This chiral cyclopentanol derivative (1), analyzed by high resolution gas chromatography performed over β-cyclodextrin stationary phase, was obtained in 38% yield (>99% e.e.). Chirality 9:321–324, 1997. © 1997 Wiley-Liss, Inc.     

First direct resolution of gossypol enantiomers on a chiral high‐performance liquid chromatography phase

The first direct resolution of gossypol enantiomers has been achieved by HPLC on a chiral stationary phase consisting of cellulose tris‐(3,5‐dimethylphenyl carbamate) coated onto microporous aminopropyl‐silica eluted in the reverse phase mode. Chirality 11:46–49, 1999. © 1999 Wiley‐Liss, Inc.