| At present,chiral compounds have been widely used in many fields such as pesticides,food and environmental protection.Many studies have shown that the enantiomers of chiral compounds have obvious differences in metabolic processes,toxicity and activity,which pose a serious threat to people's food,medicine and environmental safety.With the rapid development of the chiral compound market,the demand for single-enantiomer chiral compounds and the concern about the toxicity and activity of chiral compounds are increasing day by day.Enantiomeric resolution is facing more and more challenges.Therefore,it is of great significance to explore and develop efficient and versatile chiral separation materials.This thesis focuses on the preparation of bridged bi-?-cyclodextrin chiral stationary phase,chromatographic performance evaluation and enantiomeric resolution mechanism,mainly including the following contents:1.First,it briefly explained the threats to medicine,environment and food safety caused by the differences of enantiomers of chiral compounds,and introduced the important significance of enantiomeric separation of chiral compounds.The main resolution methods,applications and characteristics of chiral compounds are summarized.The progress and existing problems of chiral stationary phases are reviewed,with emphasis on cyclodextrin chiral stationary phases.The research progress and existing problems of cyclodextrin chiral stationary phase are summarized.2.The bridged bis(?-cyclodextrin)ligand was firstly synthesized via thiol-ene click chemistry reaction between allyl-ureido-?-cyclodextrin and 4-4'-thiobisthiophenol,which was then bonded onto a 5 ?m spherical silica gel to obtain a novel bridged bis(?-cyclodextrin)chiral stationary phase(HTCDP).The structures of HTCDP and the bridged bis(?-cyclodextrin)ligand were characterized by the elemental analysis,mass spectrometry,infrared spectrometry and thermogravimetric analysis.The performance of HTCDP in enantioseparation was systematically examined by separating 21 chiral compounds,including 8 flavanones,8 triazole pesticides and 5 other common chiral drugs(benzoin,praziquantel,1-1'-Bi-2-naphthol,Tr(?)ger's base and bicalutamide)in the reversed-phase chromatographic mode.By optimizing the chromatographic conditions such as formic acid content,mobile phase composition,p H values and column temperature,19 analytes were completely separated with high resolution(1.50?4.48),in which the enantiomeric resolution of silymarin,4-hydroxyflavanone,2-hydroxyflavanone and flavanone were up to 4.34,4.48,3.89 and 3.06 within 35 min,respectively.Compared to the native ?-CD chiral stationary phase(CDCSP),HTCDP had superior enantiomer separation and chiral recognition abilities.For example,HTCDP completely separated 5other common chiral drugs,2 flavanones and 3 triazole pesticides that CDCSP failed to separated.Unlike CDCSP,which has a small cavity(0.65 nm),the two cavities in HTCDP joined by the aryl connector could synergistically accommodate relatively bulky chiral analytes.3.Two novel bridged bis(?-cyclodextrins)were respectively synthesized via the thiol-ene click chemistry reaction of diallylamine and diallyl terephthalate as the bridging agent with mono(6-deoxy-6-mercapto)-?-cyclodextrin.Then they were respectively bonded to the surface of 5?m spherical silica gel to prepare two novel bridged bis(?-cyclodextrin)chiral stationary phase(DTCDP and HECDP).The structures of DTCDP and HECDP were characterized by high-resolution mass spectrometry,elemental analysis,thermogravimetric analysis and infrared spectroscopy.The chiral resolution performance of DTCDP and HECDP was systematically evaluated with 9 triazole pesticides and 9 flavanones chiral compounds as probes,and the related chiral resolution mechanism was discussed.The effect of flow rate and mobile phase composition on enantiomer resolution was exhaustively investigated.The efficiency,stability and reproducibility of DTCDP and HECDP were evaluated.The results demonstrated that the two chiral stationary phases had high column efficiency(13925 and 17781 plates/m),stability and reproducibility(RSD of 0.09 and 0.16%,respectively),and most of the enantiomers have been effectively resolved.Among them,the resolutions of4-hydroxyflavanone and flavanone were as high as 6.66 and 5.41 respectively.4.The novel bridged bis(?-cyclodextrins)were synthesized via the thiol-ene click chemistry reaction of diallyl terephthalate as the bridging agent with mono(6-deoxy-6-mercapto)-?-cyclodextrin.Then it was bonded to the surface of 5?m spherical silica gel to prepare a novel bridged bis(?-cyclodextrin)chiral stationary phase(NTCDP).The prepared diallyl terephthalate bridged double ?-cyclodextrin was fully derivatized with p-chlorophenyl isocyanate to synthesize the all p-chlorophenyl isocyanate-derived diallyl terephthalate bridged double ?-Cyclodextrin,and then bond it on the surface of 5 ?m spherical silica gel to prepare a fully derivatized diallyl terephthalate bridged bis ?-cyclodextrin chiral stationary phase(HPCDP).The structures of NTCDP and HPCDP were characterized by high-resolution mass spectrometry,infrared spectroscopy,elemental analysis and thermogravimetric analysis.Using 9 kinds of triazole pesticides,9 kinds of flavanone chiral compounds and 4 kinds of common chiral drugs as probes,the performance evaluation of the chiral separation of NTCDP and HPCDP was carried out in reversed-phase chromatography mode.The relevant chiral resolution mechanism was discussed,and the influence of the composition and ratio of the mobile phase on the resolution of enantiomers was studied.The results show that NTCDP has the best chiral selectivity and resolution performance,among which the resolutions of flavanone and 4-hydroxyflavanone are as high as 6.64 and 5.39,respectively. |
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