Development Of Novel Cyclodextrin Chiral Separation Materials Via “Click” Chemistry And Their HPLC Application

In this work,we prepared a series of cyclodextrin chiral separation material(CD-CSMs).The effects of spacer length,selector concentration,rim functionalities,polarity of the decorating groups and cyclodextrin orientation on enantioseparation have been investigated.(1)Three single thioether bridged cationic CSM1,CSM2 and CSM3 with different spacer length,selector concentration and rim functionalities have been prepared.The natural allyl cationic CSM2 were reacted with p-toluene-isocyanate to obtain CSM4 with multiple recognition sites.The prepared CD-CSMs have been evaluated in high performance liquid chromatography(HPLC)by separating over forty enantiomers.Most of the enantiomers were well resolved with the resolution(R_s)of 4NPh-OPr reaching 12.68 on CSM4.It could be found that the spacer length,selector concentration and rim functionalitieson have an important effect on the enantioseparation.(2)Based on the study of(1),by inducing electron-donating methoxyl or electron-withdrawing bromine/trifluoromethyl moieties,three novel cyclodextrin enantioseparation materials including per(4-trifluoromethoxy)phenyl carbamoylated-?-CD CSM(CSM5),per(4-bromo)phenylcarbamoylated-?-CD CSM(CSM6)and per(4-methoxy)phenylcarbamoylated-?-CD CSM(CSM7)were prepared via thiol-ene click chemistry.The three CD-CSMs can easily separate toluene,O-xylene and1,3,5-trimethylbenzene with the strongest retention on CSM7.In reversed-phase mode,the three CSMs exhibited completely different enantioseparation ability towards specific isoxazolines and flavonoids.4'-hydroxyflavanone was separated on CSM5with a resolution of 9.24 while 6-methoxyflavanone was best separated on CSM6(R_s=9.98).CSM7 exhibited the strongest differentiation ability towards 4NPh-2Py(R_s=9.69).The comparison study may provide some insight into the design of functional cyclodextrin materials?(3)Novel native cyclodextrin chiral stationary material(CSM8 and CSM9)with single triazole-bridge at CD C2 position and C6 position were prepared by anchoring mono(2~A-azido-2~A-deoxy)-?-CD and mono(6~A-azido-6~A-deoxy)-?-CD onto alkynyl silica via click chemistry.The effect of CD orientation on single layer CD-CSM's enantioseparation was comprehensively investigated using a commercial CD-CSM with hybrid orientation(Cyclobond I 2000)by appling in chiral HPLC.It is found that the CD orientation on silica surface plays an important role in separating different racemates.CSM9 affords best separation for isoxazolines while CSM8 better separates naringenin,hesperetin and tr?ger's base.CSM9 and Cyclobond I 2000 show comparable separation ability for dansyl amino acids while poor separation was found on CSM8.Besides,we found that CD orientation may strongly influence the elution order for some specific analytes.