Preparation And Evaluation Of Novel Amino Acid Sulfamide Chiral Stationary Phases

The resolution of chiral enantiomers is of great significance in the research,production and quality control of drugs.Chiral liquid chromatography separation technology is widely used in the resolution of chiral enantiomers,whose core is the chiral stationary phase.Chiral stationary phases based on amino acid arylamide derivatives have been widely used in the study of brush-type chiral stationary phases,but chiral stationary phases based on sulfonamide derivatives are rarely reported.Studies have shown that certain chiral sulfonamide compounds exhibited excellent chiral selectivity in organic catalysis,and may also become excellent chiral selectors of stationary phases.In this paper,a series of new amino acid sulfonamide chiral stationary phases were designed and synthesized using amino acids as chiral sources.Their chiral selectivities were systematically evaluated and compared,and their chiral recognition mechanisms were discussed.The first part of the thesis work carried out the preparations of the stationary phase.The three amino acids(L-leucine,L-proline,L-phenylalanine)were derivatized with various aromatic sulfonyl chlorides,and the corresponding amino acid sulfonamide chiral stationary phases were prepared.Three of these chiral structures were selected to prepare the corresponding C2 symmetric amino acid sulfonamide chiral stationary phases.The synthetic routes,the optical purity of the intermediates and the bonding amount of the chiral selector were investigated and characterized so as to provide a basis for subsequent evaluation work.In the second and third parts of the thesis work,the single-chain and C2 symmetric di-substituted amino acid sulfonamide chiral stationary phases were evaluated,respectively,and 74 enantiomers were selected to evaluate their chiral separation performance.And the impact of the structures of chiral selectors on chiral resolution was studied.Compared with benzoyl,the use of benzenesulfonyl significantly improved the chiral separation performance of the stationary phase;on the one hand,naphthalenesulfonyl and quinolinesulfonyl enhanced the chiral separation of some enantiomers due to the stronger ?-? interaction,on the other hand,they will also reduce the chiral separation of some enantiomers with greater steric hindrance due to the larger steric hindrance;The stationary phase,whose binding arm was introduced by a phenyl group,had better resolution performance for many C2 symmetric enantiomers,which was most likely due to the steric hindrance effect and ?-? interaction between the stationary phase and the enantiomer,which is more conducive to chiral recognition.The three C2 symmetric chiral stationary phases showed better chiral resolution performance than the corresponding single-chain substituted chiral stationary phases,especially for the chiral separation of C2 symmetric enantiomers.The C2 symmetric stationary phase with L-leucine acid as the chiral source showed the best chiral resolution performance,and achieved the separation of 58 chiral enantiomers.In addition,the influence of the mobile phases and types and proportions of alcohol modifiers on chiral resolution was studied.The chiral recognition mechanisms of several single-chain substituted and C2 symmetric chiral stationary phases were investigated by 1H NMR and 1H-1H NOESY NMR.