| Chiral preparative chromatography is the most commonly used method for the resolution of chiral compounds.The polysaccharide chiral stationary phase is considered to be the stationary phase with the best chiral separation effect and the widest application range.In order to study the adsorption behavior of polysaccharide stationary phase in non-linear chromatography,this thesis optimized the determination method of enantioselective and nonselective adsorption on the polysaccharide stationary phase based on the two-site model.The chiral stationary phase was studied from the source of amylose and the coating amount of amylose derivatives.Corey lactone diol,cloprostenol and muscone were prepared by chiral resolution at the semi-preparation level.The main research contents of the thesis are as follows:The adsorption of chiral molecules on the chiral stationary phase includes enantioselective adsorption and non-selective adsorption.This thesis proposed the subtraction fitting method based on the two-site model of chiral adsorption to determine the enantioselective and nonselective adsorption of chiral molecules on the surface of the stationary phase.The adsorption isotherm of methyl mandelate enantiomer was determined by frontal analysis by characteristic point(FACP).The direct fitting method and the subtraction fitting method were used to calculate the adsorption isotherm equation,and the adsorption parameters obtained by the subtraction fitting method were more in line with the two-site model.The adsorption of methyl mandelate on the enantioselective sites conforms to the Langmuir model,and the adsorption on the non-selective sites conforms to the Tóth or the Langmuir-Freundlich model.The results showed that the subtraction fitting method can better reflect the difference in the adsorption of enantiomers on the surface of the stationary phase.This thesis studied the influence of the source of amylose and the coating amount of amylose derivatives on the chiral separation.The amyloses in corn starch,wheat starch,potato starch,mung bean starch,and pea starch were extracted by enzymolysis and butanol method,and the amyloses were characterized by ultraviolet absorption spectroscopy and gel chromatography.The results show that potato amylose has the highest blue value and average molecular weight.Using these amyloses,13 chiral columns coated with amylose tri-(3,5dimethylphenylcarbamate)(ADMPC)and amylose tri-[(S)-α-methylbenzylcarbamate](ASMBC)were prepared.The comparison results show that the stationary phase prepared from potato amylose has the strongest chiral resolution ability,and the greater the amount of derivative coating,the greater the enantiomer retention factor.The chiral separation of Corey lactone diol was studied.Various factors affecting separation were investigated on high performance liquid chromatography and supercritical chromatography,including the type of polysaccharide stationary phase,the coating amount of polysaccharide derivatives,and the composition of mobile phase,temperature,back pressure,type and concentration of modifier,etc.The relationship between enantioselective adsorption,non-selective adsorption and the coating amount of ADMPC was determined.The results showed that the saturated adsorption capacity increased with the increase of the coating amount.The true selectivity of ADMPC-20 was the highest,but the true selectivity decreased with the increase of the coating amount.The chiral preparation of Corey lactone diol was verified at semi-preparation level.The chiral preparation efficiency of ADMPC-30 was 1.536 kg racemate/kg chiral stationary phase/day.The chiral separation of cloprostenol was studied,the type of chromatographic column,mobile phase mode,mobile phase composition,column temperature and other chromatographic conditions were investigated,and the polar organic mobile phase and ADMPC-coated chromatographic column were determined to be suitable separation system.It is found that adding a small amount of water to the organic mobile phase can greatly improve the separation selectivity.Through the determination and analysis of adsorption isotherms,a small amount of water in the mobile phase will greatly reduce the adsorption equilibrium constant of the weakly retained(-)-cloprostenol and the stationary phase chiral sites,resulting in a significant increase in selectivity.The mobile phase system and the preparation column with ADMPC-30 were used for chiral preparation,the preparation efficiency was 0.25 kg racemate/kg chiral stationary phase/day.The chiral preparation of muscone has been studied,and the chromatographic column coated with ASMBC can effectively separate the optical enantiomers of muscone.The effects of chromatographic conditions such as the coating amount of polysaccharide derivatives and mobile phase composition on the chiral separation were investigated.After condition optimization,the chiral chromatographic preparation conditions of muscone were determined,and the chiral separation of muscone was completed on the preparative column.The preparation efficiency was 133 mL racemate/kg chiral stationary phase/day. |
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