Preparation And Enantioseparation Of Regioselective Cyclodextrin Derivatives As Chiral Stationary Phases

Chiral compounds were found to be existed in biosystem universally and were closely associated with people's health.The two enantiomers usually show distinct physiological and pharmacological activities,thus it is important to obtain a single pure chiral enantiomer.High performance liquid chromatography(HPLC)is the most widely used method in chromatographic separation and the cyclodextrin type of CSP showed unique advantages on the separation of chiral compounds due to its special structure.Fistly,a series of cyclodextrin derivatives having different substituents at 2,3-and6-positions were synthesized by regioselective reaction with the?-cyclodextrin as raw material,different substituted phenyl isocyanate as modifier.The structures of?-cyclodextrin derivatives were characterized by Fourier transform infrared spectrometer(FT-IR)and nuclear magnetic resonance hydrogen spectrum(~1H NMR).Then,the immobilized CSPs based on the?-cyclodextrin derivatives were prepared by coating on ammonia propyl silicone,and immobilization.The chiral columns were prepared by packing procedures.The immobilized efficiency was tasted by thermo gravimetric analysis(TGA).Finally,the chiral recognition abilities of three series of 12 regioselective?-cyclodextrin derivative CSPs were tested through 11 racemates under normal-phase HPLC.The results of enantioseparation show that regioselective?-cyclodextrin derivative CSPs optimum chromatographic separation conditions were n-hexane/isopropanol=99/1(v/v)as the mobile phase.Different substituent groups at 6-position have a great influence upon enantiomer separation when substituent groups were same at 2,3-positions.For 2,3-diphenyl carbamate?-cyclodextrin derivative CSPs,the chiral separation abilities for the studied racemates were better than others with the maximal separation factor?values of 1.40,when electron-withdrawing substituents 3,5-dichlorophenylcarbamate group was at 6-position of theglucose.Enantioseparationabilitiesdecreasedwiththedecreasingof electron-withdrawing substituents.For 2,3-di(3,5-dimethylphenyl carbamate)-?-cyclodextrin derivative CSPs,when electron-withdrawing substituents 4-chlorobenzene carbamate group was introduced at 6-position,the CSPs obtained separation for the majority of enantiomers and displayed better separation abilities than others with the maximal separation factor?values of 1.72.While separation ability declined distinctly with an increase of electron-withdrawing substituents.For 2,3-di(3,5-dichlorobenzene carbamate)-?-cyclodextrin derivative CSPs,the chiral separation abilities were better than others with the maximal separation factor?values of 2.06 when phenyl carbamate group was at 6-position.And separation ability reduced with an increase of electron-withdrawing or electron-donating substituents on benzene ring.