NMR and computational studies of chiral discrimination by amylose tris(3,5-dimethylphenylcarbamate).
Proton NMR and simulations were combined to study the origin of chiral selectivity by a polysaccharide used in a commercial chromatographic stationary phase: amylose tris(3,5-dimethylphenylcarbamate). This material has unusually high enantioselectivity for p-O-tert-butyltyrosine allyl ester, which is activated by the presence of an acid. Proton NMR spectra agreed with the HPLC in showing that the l-enantiomer interacts much more strongly with the polysaccharide and that acidity switches on the selectivity. 2D NOESY spectra revealed which protons of each enantiomer and the polysaccharide were in proximity, and these spectra revealed folding of the l-enantiomer. Computations generated energy-minimized structures for the polysaccharide-enantiomer complexes, independently predicting folding of the l-enantiomer. Molecular dynamics simulations 2 ns in duration, repeated for three different energy-minimized structures, generated pair distribution functions that are in excellent agreement with the 2D NOESY spectra. The modeling studies revealed why acidity switches on chiral selectivity and minimally affects the chromatographic retention time of the unfavored d-enantiomer. The results comprise the first case of a chiral separation by a commercial polysaccharide stationary phase being explained using a combination of 2D NOESY and simulations, providing excellent agreement between experiment and computation and lending detailed molecular insight into enantioselectivity for this system.
Ye
Yun K
YK
Bristol-Myers Squibb Company, 1 Squibb Drive, New Brunswick, New Jersey 08903, USA.
Bai
Shi
S
Vyas
Shyam
S
Wirth
Mary J
MJ
D000688:Amylose / Q000031:analogs & derivatives* / Q000737:chemistry; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D015394:Molecular Structure; D048448:Phenylcarbamates / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013997:Time Factors
D048448:Phenylcarbamates; C080033:Chiralpak AD; D000688:Amylose