Preparation And Application Of Teicoplanin Functionalized Polymeric Monolith

The enantioseparation and analysis of chiral compounds remains an important topic in research and application area.It is mainly due to the importance of chiral compounds,for example,related to human health,and the limitations of conventional separation methods.In fact,chiral recognition can only be achieved in the presence of a chiral environment.So far,although a large number of chiral selectors have been used for enantioseparation,the research of CSPs is still a hot topic.Moreover,in recent years,the chiral monolithic column has attracted attention due to its simple preparation process,good mechanical strength and permeability.Therefore,the aim of this thesis is to design and prepare a teicoplanin chiral monolith with high chiral recognition.Based on this research,the enantioseparation of drugs was contrast between the commercialized teicoplanin capillary packed column and teicoplanin monolith.In addition,a higher purity teicoplanin monolith was prepared for the resolution of chiral compounds.Chapter 1.The importance of chiral separation and the types of chiral stationary phases have been systematically introduced.The chiral stationary phase of macrocyclic glycopeptides has been reviewed,especially for teicoplanin.At the same time,the research progress of chiral organic polymer monolithic column and the advantages and disadvantages of capillary packed column have been briefly introduced.Chapter 2.The monomer 2-isocyanatoethyl methacrylate（ICNEML）-teicoplanin was synthesized,and then thermally co-polymerized with the crosslinker ethylene glycoldimethacrylate（EDMA）,porogens（methanol and dimethylsulfoxide）and initiator（AIBN）within 100μm I.D.fused silica capillary to prepare the poly（I-T-co-EDMA）monolith.The poly（I-T-co-EDMA）monolith was characterized using Nano-LC and scanning electron microscopy.In order to study the enantioseparation capability of the poly（I-T-co-EDMA）monolith,28 chiral compounds were analyzed under reversed-phase and polar-organic phase modes by nano-liquid chromatography（nano-LC）.Comparing to the enantioseparation results of amino alcohols on other teicoplanin-CSPs,it was found that the enantioselectivity of the same amino alcohol compounds on poly（I-T-co-EDMA）monolith would be the same as that of other teicoplanin-CSPs which have been reported,such as alprenolol（1.22 vs 1.14）,isoproterenol（1.3 vs 1.22）,propranolol（1.22 vs 1.15）,and betaxolol,clenbuterol,tertatolol,carteolol,metipranolol and talinolol（R_s=1.14-1.92,α=1.15-1.32）were ennatiosepareted on the teicoplanin columns for the first time,which broadens the range of application of teicoplanin-CSP.Chapter 3.In order to compare the selective behavior of teicoplanin-CSP in different substrates,the commercial teicoplanin capillary packed column was utilized to enantioseparate mandelic acid,N-derivatized amino acids and amino alcohols.Comparing the selective behavior of the same compound on two substrates,it was found that the amino alcohols and the mandelic acid derivatives have similar selectivity on the teicoplanin chiral column of two different substrates,while the mandelic acid and N-derivatized amino acids are quite different.Chapter 4.In chapter 2,teicoplanin was a mixture,including five structurally similar compounds,T_A2-1,T_A2-2 and T_A2-3（isomer）,T_A2-42-4 and T_A2-5（isomer）,the main component is T_A2-2.After the ICNEML modified,the corresponding I-T products are I-T_A2-1,I-T_A2-2 and I-T_A2-3（isomer）,I-T_A2-4 and I-T_A2-5（isomer）,the main component I-T_A2-2 is about 45%.In order to study the effect of ennatioseparation after purification of teicoplanin chiral selector,the raw material purification by wet method.The I-T products were obtained by modifying the ICNEML with three structures,I-T_A2-1,I-T_A2-2 and I-T_A2-3（isomer）,wherein the content of I-T_A2-2 is about 82%.The poly(I-T_82%-co-EDMA)monolith was prepared and used for the enantioseparation of chiral drugs.Comparing the enantioseparation of the same compound on the poly（I-T-co-EDMA）monolith,it was found that the poly(I-T_82%-co-EDMA)monolith showed similar selectivity to most N-derivatized amino acids and higher enantioresolution of mandelic acidsChapter 5.The conclusions of this research were described.And the future work of teicoplanin-CSP is also prospected.