Chiral separation with polysaccharide based amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase

Polysaccharides are now the most widely used class of stationary phases for chiral separations, yet molecular insight into their chiral selectivity has been lacking. A study was performed for amylose tris(3,5-dimethylphenylcarbamate) or, ADMPC, chiral stationary phase (CSP), to obtain information on how chiral discrimination occurs using chromatography, NMR and computational methods. Chromatographic study reveals that the mobile phase achiral additive played an important role in the enantioselectivity for polysaccharide-based stationary phases. The effects of acidic additive ethanesulfonic acid and basic additive n-butylamine were studied for a wide variety of chiral compounds using ADMPC CSP. The mobile phase consisted of hexane:ethanol, 90:10 (v:v). The additives typically had minimal effects, with one exception: the acidic additive had an enormous impact on the chiral selectivity of amino acid esters. The improved chiral selectivity was largely due to the longer retention of the later eluting enantiomer. The retention behavior of amines indicated that the higher selectivity for amino acid esters was due to increased hydrogen bonding donation by the amine group of the analyte. Retention behaviors for a range of structures point to steric hindrance as the third interaction to comprise the requisite three interactions in chiral recognition.; Proton NMR was also used to study the origin of chiral selectivity. The structure of ADMPC was studied with and without the presence of ethanesulfonic acid in chloroform. It was found that there were no tertiary structure changes for the amylose tris(3,5-dimethylphenylcarbamate) in the presence of ethanesulfonic acid. The enantioselectivity of ADMPC for p-O-tert-butyl tyrosine allyl ester was also studied with and without the presence of ethanesulfonic acid in chloroform. The Proton NMR spectra shows that the ethanesulfonic acid greatly enhances enantioselectivity, which correlates with HPLC. 2D NOESY spectra shows that the polysaccharide favors the L enantiomer, which is also in agreement with HPLC. This further reveals which protons of the polysaccharide and enantiomer are in proximity.; The interactions between p-O-tert-butyl tyrosine allyl ester and ADMPC were further studied with and without the presence of ethanesulfonic acid in chloroform using molecular mechanics and molecular dynamics simulations. Molecular mechanics simulations generated energy-minimized structures for the polysaccharide-enantiomer complexes; molecular dynamics simulations provided energy distributions and pair correlation functions, all of which agree qualitatively with the NMR and HPLC results. (Abstract shortened by UMI.)...