Preparative Enantioseparation of β-Substituted-2-Phenylpropionic Acids by Countercurrent Chromatography With Substituted β-Cyclodextrin as Chiral Selectors.
Preparative enantioseparation of four β-substituted-2-phenylpropionic acids was performed by countercurrent chromatography with substituted β-cyclodextrin as chiral selectors. The two-phase solvent system was composed of n-hexane-ethyl acetate-0.10 mol L-1 of phosphate buffer solution at pH 2.67 containing 0.10 mol L(-1) of hydroxypropyl-β-cyclodextrin (HP-β-CD) or sulfobutylether-β-cyclodextrin (SBE-β-CD). The influence factors, including the type of substituted β-cyclodextrin, composition of organic phase, concentration of chiral selector, pH value of the aqueous phase, and equilibrium temperature were optimized by enantioselective liquid-liquid extraction. Under the optimum separation conditions, 100 mg of 2-phenylbutyric acid, 100 mg of tropic acid, and 50 mg of 2,3-diphenylpropionic acid were successfully enantioseparated by high-speed countercurrent chromatography, and the recovery of the (±)-enantiomers was in the range of 90-91% for (±)-2-phenylbutyric acid, 91-92% for (±)-tropic acid, 85-87% for (±)-2,3-diphenylpropionic acid with purity of over 97%, 96%, and 98%, respectively. The formation of 1:1 stoichiometric inclusion complex of β-substituted-2-phenylpropionic acids with HP-β-CD was determined by UV spectrophotometry and the inclusion constants were calculated by a modified Benesi-Hildebrand equation. The results showed that different enantioselectivities among different racemates were mainly caused by different enantiorecognition between each enantiomer and HP-β-CD, while it might be partially caused by different inclusion capacity between racemic solutes and HP-β-CD.
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Shengqiang
S
Tong
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Hu
H
Zhang
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Dongping
D
Cheng
D003377:Countercurrent Distribution / Q000379:methods*; D010666:Phenylpropionates / Q000737:chemistry / Q000302:isolation & purification*; D013237:Stereoisomerism; D047392:beta-Cyclodextrins / Q000737:chemistry*
D010666:Phenylpropionates; D047392:beta-Cyclodextrins; C013025:hydratropic acid; C031215:betadex
countercurrent chromatography; enantiorecognition; enantioseparation; substituted β-cyclodextrin; β-substituted-2-phenylpropionic acids