Enantioseparation Of Chiral Drugs On Chiral Stationary Phases And The Mechanism Study

The enantiomeric resolution of sixβ₂-agonists including bambuterol, clenbuterol, clenproperol, fumoterol, mabuterol and terbutaline was studied on three macrocyclic antibiotic chiral stationary phases (CSPs): Chirobiotic V, T and R. The enantiomeric resolution of fiveβ₂-agonists including bambuterol, clenbuterol, clenproperol, fumoterol and mabuterol mentioned above was studied on two Pikle-type CSPs: Pirkle-1J andα-Burke-2. The enantiomeric resolution of fiveβ₂-agonists mentioned above except terbutaline and sixβ-blockers including propranolol, atenolol, acebutolol, pindolol, alprenolol and oxprenolol was investigated on Crown ether-NH and N-CH₃ CSPs. A new Pirkle-type CSP was prepared and applied to resolve a number of N-(3,5-dinitrobenzoyl)-α-amino amides and N-acyl-1-aryl-l-aminoalkanes and found to be effective. The chiral recognition mechanism for different enantioresolution was proposed. 1,Enantioresolution ofβ₂-agonists on macrocyclic antibiotic CSPsThe enantiomeric resolution of sixβ₂-agonists was studied on three macrocyclic antibiotic chiral stationary phases (CSPs): Chirobiotic V, T and R. Factors affecting the enantioresolution, such as the separation mode, composition of mobile phase and column temperature were investigated. No enantioresolution was achieved for the sixβ₂-agonists on Chirobiotic R CSP. On Chirobiotic V and T CSPs, the polar organic mode (POM) was proved to be the best, with methanol-acetic acid-triethylamine (100:0.01:0.01, v/v/v) as the mobile phase, the enantiorners of all the sixβ₂-agonists were successfully separated, and the simultaneous enantioseparation ofβ₂-agonist mixture was achieved. The thermodynamic parameters ofβ₂-agonists in this mode were investigated, the enantioselectivity was proved to be enthalpocally controlled. The chiral recognition mechanism was discussed, ionic interaction between the CSPs andβ2-agonists was confirmed to be the dramatic interaction responsible for the chiral discrimination.2. Enantioresolution ofβ₂-agonists on Pirkle-type CSPsThe enantiomeric resolution of fiveβ₂-agonists was studied on two Pikle-type CSPs: Pirkle-1J and or-Burke-2. Factors affecting the enantioresolution, such as the type and concentration of the salts additives, the content of the organic solvents and temperature were investigated. Under the optimized chromatographic condition, enantiomers of fiveβ₂-agonists were successfully separated on or-Burke-2 CSE while only twoβ₂-agonist enantiomers were resolved on Pirkle-1J CSE The thermodynamic parameters ofβ₂-agonists on two CSPs were investigated, the enantioselectivity was proved to be enthalpocally controlled. The chiral recognition mechanism was discussed,Ï€-Ï€interaction and hydrogen binding between the CSPs andβ₂-agonists were confirmed to be the interactions responsible for the chiral discrimination.3,Enantioresolution ofβ₂-agonists andβ-blockers on crown ether CSPsThe enantiomeric resolution of fiveβ₂-agonists and sixβ-blockers was investigated on Crown ether-NH and N-CH₃ CSPs. By varying the mobile phase composition and temperature, the enantiomers of all analytess were successfully separated on Crown ether-NH CSP, while only enantiomers ofβ-blockers were partly resolved on Crown ether-N-CH₃ CSP, the enantioresolution ofβ₂-agonists was not achieved on it. The thermodynamic parameters ofβ₂-agonists andβ-blockers on the CSPs were investigated, the enantioselectivity was proved to be entropically controlled. The chiral recognition mechanism was discussed, hydrogen binding, ionic interaction and inclusion interaction between the CSPs and the analytes were confirmed to be the interactions responsible for the chiral discrimination.4. Preparation and application of a new Pirkle-type ehiral stationary phaseA new high-performance liquid chromatographic Pirkle-type chiral stationary, phase was prepared starting from R-(+)-1,1'-binaphthyl-2,2'-diamine. The CSP thus prepared was successfully applied to resolve a number of N-(3,5-dinitrobenzoyl)-α-amino amides and N-acyl-1-aryl-1-amino alkanes and found to be effective. The chiral recognition mechanism was proposed to beÏ€-Ï€interaction and simultaneously hydrogen bonding interactions between the CSP and the analytes.