Preparation And Enantioseparation Characteristics Of Chiral Separation Materials Drived From Chitosan Derivatives

High-performance liquid chromatography based on chiral stationary phase(CSP)has become one of the most effective method for the enantioseparation of chiral compounds.Among lots of developed CSPs,coated-type ones derived from polysaccharide derivatives have been applied most widely up till now,owing to their strong enantioseparation capability and high loadability.The CSPs prepared from cellulose tris(3,5-dimethylphenylcarbamate)(CDMPC)and amylose tris(3,5-dimethylphenylcarbamate)(ADMPC)exhibit excellent enantioseparation capability towards most of racemates and accordingly have become typical ones of coated-type CSPs.However,since these derivatives of cellulose and amylose can be dissolved or highly swollen in organic solvents,the related CSPs can only work in a limited range of eluents with a short service life.According to reported literatures,the CSPs derived from chitosan derivatives,the ones with alkylurea substituents on 2-position in particular,have been proven not only to possess satisfactory tolerance against organic solvents,excellent enantioseparation performance for a wide range of racemates but also.Recently,a series of chitosan 3,6-bis(arylcarbamate)-2-(alkylurea)s with straight-chain alkyl,cyclic alkyl and aryl groups connected to the urea at 2-position of glucose residue in chitosan were reported by this laboratory,yet this class of chitosan derivatives with branched-chain alkyl group has not been reported.Therefore,in order to develop new CSPs with excellent separation capability as well as high tolerance to organic solvents and investagate the relationship between structure and performance,two groups of chitosan bis(arylcarbamate)-(isobutylurea)were synthesized in this thesis.The structural dependence including the different suprastructures caused by substituents at 2-position and benzene ring and the molecular weight of chitosan on the performance of the prepared CSPs was preliminarily clarified.The works implemented in this thesis are summarized as follows:1.Two kinds of chitosan(isobutylurea)were prepared with chitosans of different viscosity-average molecular weights.Then,chitosan bis(methylphenylcarbamate)-(isobutylurea)s with higher and lower molecular weights wee synthesized by using four methyl-substituted phenylisocyanates.Two groups of CSPs were prepared with the prepared chitosan derivatives,and the performances were evaluated.The CSPs with the chitosan derivatives of lower molecular weight bear better enantioseparation capabilities than the ones of higher molecular weight;the CSPs with the chitosan derivatives of higher molecular weight possess higher tolerance against organic solvents.All CSPs showed very good enantioseparation capability.Especially,the CSPs prepared from chitosan bis(4-methylphenylcarbamate)-(isobutylurea)and chitosan bis(3-chloro-4-methylphenylcarbamate)-(isobutylurea)demonstrated an excellent separation capability which is equivalent to that of Chiralcel OD–H.In addition,the swelling capacity of the two groups of chiral selectors,i.e.chitosan bis(3-chloro-4-methylphenylcarbamate)-(isobutylurea)s,was tested in some organic solvents.It was found that,in each group of corresponding CSPs,the CSP prepared from the chiral selector with the highest swelling capacity bear the best separation performance.Therefore,higher swelling capacity of chiral selectors is beneficial to chiral separation.2.A series of chitosan bis(chlorophenylcarbamate)-(isobutylurea)s were synthesized with four chlorophenyl isocyanates and chitosan(isobutylurea).The CSPs were prepared with the resulting derivatives.In combination with the separation performance comparison of the CSPs derived from chitosan bis(methylphenylcarbamate)-(isobutylurea)s,it was observed that the position,type and number of the substituents on benzene ring in chitosan derivatives impacted the enantioseparation capability and tolerance towards eluent.The CSPs prepared from chitosan derivatives with 3-chlorosubstituent and 3,5-dichlorosubstituent exhibited better separation performance than the ones with methylsubstituted chitosan derivatives.However,a reversed trend was observed for the CSPs prepared from the chitosan derivatives with 4-chlorosubstituent and 3,4-dichlorosubstituent.Besides,the swelling capacity of the chitosan derivatives with chlorosubstituent in organic solvents was generally higher than that of the ones with methylsubstituent,revealing that the tolerability of the chitosan derivatives with chlorosubstituent against organic solvents is lower than that of the chitosan derivatives with methylsubstituent.Yet,the CSPs prepared from the chitosan derivatives with chlorosubstituent still could work in 100% ethyl acetate,100% acetone and the mobile phases containing a certain propotion of tetrahydrofuran(THF).3.The chitosan derivative with the best separation performance and high tolerance to organic solvents was selected to be coated on 5-?m macroporous 3-aminopropyl silica gel affording a new CSP.Some chiral drugs or chiral intermediates for drugs were tried for their enantioseparation by the CSP.It was found that the CSP could recognized the enantiomers of dipine-type and conazole-type drugs,thus displaying its practicability.In summary,a series of chitosan derivatives with branched-chain at 2-position of glucose residue were prepared.Some CSPs with excellent enantioseparation performance and high tolerance towards organic solvents were developed.The influence of substituents at 2-position and benzene ring and molecular weight of chitosan on the separation performance and tolerance of chitosan bis(arylcarbamate)-(alkylurea)s was discussed in detail.It was also found that the CSP with the best separation performance could be used for the enantioseparation of dipine-type and conazole-type drugs.