Synthesis And Enationsparation Performance Of Chiral Stationary Phases Based On Cyclopropylformylated/cyclopentylformylated Chitosans

Chiral stationary phase(CSP)is a critical part of chiral high-performance liquid chromatography(HPLC).The CSPs based on polysaccharides derivatives attract much attention due to their excellent separation performance.Therefore,it is very important to study the preparation and the structural dependence on the properties of novel coating-type CSPs derived from polysaccharides derivatives.In order to develop novel CSPs with good enantioseparation capability and satisfactory tolerability to organic solvents,in this work,seventeen CSPs derived from chitosan bis(arylcarbamate)-(amide)were prepared,in which the degree of deacetylation(D.D.)of the chitosan as the starting material was above 98%.These chitosan derivatives and corresponding CSPs have not been reported.The enantioseparation capability and tolerability to organic solvent were evaluated.The structural dependence on the performance of these CSPs was discussed.The implemented works can be summarized as follows:(1)The chitosan with an ultra-high D.D.(above 98%)was prepared by employing n-pentanol-NaOH and water-NaOH as the reaction systems.The viscosity-average molecular weight(M ?)of the chitosan(named as C1)prepared in a n-pentanol/NaOH reaction system was 2.4×105,and was 1.4×105 after C1 was further degraded in an aqueous H2O2 solution where the chitosan was named as C2.The chitosans(named as C3,C4 and C5)were obtained by varying the reaction conditions in the reaction systems of water-NaOH,and their M ? were 7.8×105,9.2×105 and 1.0×106 respectively.The chitosan(named as C6)with the M? of 2.9×105 was prepared by combining the above two reaction systems.Chitosan C1,C2,C3 and C4 were modified with an excess of cyclopropanecarboxylic anhydride yielding four new N-acetylated chitosan that were,respectively,named as I(a),I(b),I(c)and I(d).The N-acetylated chitosans were characterized by FT-IR,1H NMR and elemental analysis,and the results showed that the amino groups on the 2-C of structural units of the chitosans were selectively and completely acylated.Five novel chiral selectors were prepared by derivatizingN-acetylated chitosan I(a)with phenyl isocyanate and other four methyl-containing phenyl isocyanates.The derivatives were then coated on 3-aminopropyl silica gel to obtain the first series of CSPs.These chiral selectors were insoluble in chloroform,acetone,ethyl acetate,etc.,however,swelled in tetrahydrofuran(THF)at different extent.The chiral recognition and enantioseparation capability of the above CSPs were investigated by HPLC.The chiral recognition and separation capability of the CSP derived from chitosan bis(3-chloro-4-methylphenylcarbamate)-(cyclopropylformylamide)was better than that of CSPs derived from cellulose tris(3,5-dimethylphenylcarbamate)(CDMPC)and amylose tris(3,5-dimethylphenylcarbamate)(ADMPC)which were well known for their most powerful chiral recognition and separation capability so far.There were another two CSPs whose separation capability was generally equivalent to that of the CSPs of CDMPC and ADMPC.The tolerability of the CSP which had the most powerful chiral separation capability was evaluated towards organic solvents.This CSP could be analyzed with a mobile phase of 100% actone,100% ethyl acetate,and 80% THF,therefore exhibiting a high tolerability against organic solvent.(2)Six novel chiral selectors were prepared by modifying I(b),I(c)and I(d),respectively,with four chloro-containing phenyl isocyanates,4-chloro-3-trifluoromethylphenyl isocyanate and 4-trifluoromethoxylphenyl isocyanate.The derivatives were then coated on 3-aminopropyl silica gel to obtain new CSPs.The chiral separation capability of these six CSPs was overall better than that of the CSPs of CDMPC and ADMPC.The CSPs derived from chitosan bis(4-chlorophenylcarbamate)-(cyclopropylformylamide)and chitosan bis(4-trifluoromethoxylphenylcarbamate)-(cyclopropylformylamide)could be analyzed with a mobile phase of 100% THF.Tolerability of these two CSPs against organic solvents was better than that of the CSP of chitosan bis(3-chloro-4-methylphenylcarbamate)-(cyclopropylformylamide)mentioned in section(1).(3)Chitosan C5 and C6 were derivatized with an excess cyclopentanecarboxylic anhydride to produce cyclopentylformylated chitosans I(e)and I(f).Similarly,the amino groups on the 2-C of structure units of chitosan were selectively and completely acylated.N-Acetylated chitosan I(e)was modified with 4-chloro-3-trifluoromethylphenyl isocyanate and 4-trifluoromethoxylphenyl isocyanate respectively,and I(f)was modified with four only chloro-containing phenyl isocyanates,respectively,to afford six novel chiral selectors.The derivatives were then coated on 3-aminopropyl silica gel to obtain new CSPs.These CSPs had better chiral separation capability than that of the CSPs of CDMPC and ADMPC.The swelling and solubility properties of the as-prepared chiral selectors in common organic solvents were similar to that of the chiral selectors in(2).In summary,compared with the coating-type CSPs of CDMPC and ADMPC,most of the CSPs prepared in this work exhibited an equivalent or a better chiral recognition capability,and a higher tolerability against organic solvents was well.Most CSPs can be applied for detection and batch separation.