【作者】 张瑛；

【导师】 王勇；

【作者基本信息】 天津大学 ， 化学， 2022， 硕士

【摘要】 随着医学,农药等领域对光学纯异构体需求的迅速增加,开发具有普适性、经济高效的手性拆分方法显得尤为重要。高效液相色谱法（HPLC）用于手性拆分的核心是多种手性固定相（CSPs）的制备,具有分离速度快、分离模式多样和适用范围广等优点,在手性分离领域备受研究者青睐。本研究基于硫醚键合环糊精类HPLC固定相（CD-CSPs）的发展基础,利用“巯基-烯”点击反应制备了多种新型CD-CSPs;同时将超分子CD单元集成到共价有机骨架（COFs）晶体结构中制备了环糊精共价有机骨架（β-CD COF）,并考察了它们的手性识别能力。（1）采用“巯基-烯”反应将七（6-脱氧-6-N-烯丙基咪唑）-β-CD-氯化物与巯基硅胶共价键合,制备了两种不同固载量的多电荷阳离子CD-CSPs（CSP 1和CSP 2）,之后进行羟基的后衍生官能化将CSP 2改性得到两种新型的衍生多电荷阳离子CD-CSPs（CSP 3和CSP 4）。通过红外光谱（FT-IR）、固体核磁(¹³C SSNMR)、热重（TGA）和元素分析等测试证明了系列CSPs的成功制备。在HPLC的不同洗脱模式下,考察了这类固定相对多种类型分析物的手性识别能力,CSP2对丹磺酰氨基酸（Dns-氨基酸）类样品分离效果较好,其中Dns-Thr和Dns-Aca的选择因子（α）可达到2.86和1.97,优于单电荷阳离子CD-CSP的分离效果。（2）采用“巯基-烯”反应在硅胶表面自下而上地构建桥连CD双分子层,制备了双层硫醚桥连CD-CSP（TIBCD-CSP）和相应底层、顶层的单层CD-CSPs（MAICD-CSP和HMDCD-CSP）。TIBCD-CSP可以分离20种异噁唑啉类对映体,其中12种可达到基线分离（R_S>1.5）,对于Dns-氨基酸类,R_S均大于3.1。此外,通过比较三种CSPs在相同条件下对多种对映异构体的分离能力,探究了双层桥连CD-CSP中两层CD空腔存在的协同作用对手性分离的影响。（3）通过七-（6-氨基-6-脱氧）-β-CD和对苯二甲醛的席夫碱反应制备β-环糊精共价有机骨架（β-CD COF）,以FT-IR、¹³C SSNMR、粉末X射线衍射（PXRD）、TGA、扫描电子显微镜（SEM）、透射电子显微镜（TEM）和比表面积孔径分析（BET）等多种表征手段证明了β-CD COF是由CD单元有序堆积的晶体材料。并且采用多种方式将其固载到硅胶表面或与硅胶共混制备合适的色谱柱填料,应用到色谱手性分离领域,对部分黄烷酮类（Flas）和异噁唑啉类对映体表现出一定的手性识别能力。更多还原

【Abstract】 With the rapidly growing demand for optically pure compounds,the development of efficient,economical and convenient chiral separation methods has become an important research effort.High-performance liquid chromatography（HPLC）based on chiral stationary phases（CSPs）is favored by researchers because of its fast separation speed,diverse separation modes and wide application range.In this study,based on the current development of cyclodextrin-based high-performance liquid chromatography stationary phases（CD-CSPs）,a variety of novel CD-CSPs were prepared using the“thiol-ene”click reaction;at the same time,cyclodextrin covalent organic framework（β-CD COF）was prepared by integrating supramolecular CD units into the crystal structure of covalent organic framework（COFs）,and their chiral recognition ability was investigated.（1）Two kinds of multi-charged cationic CD-CSPs（CSP 1 and CSP 2）with different CD loadings were prepared by covalent bonding of hepta（6-deoxy-6-N-allylimidazole）-β-CD-chloride with thiol silica gel using the“thiol-ene”reaction,and then CSP 2 was modified by post-derivative functionalization of hydroxyl groups to obtain two novel derivative multi-charged cationic CD-CSPs（CSP 3 and CSP 4）.The successful preparation of the series CSPs is proved through infrared spectrum（FT-IR）,solid nuclear magnetic(¹³C SSNMR),thermal analysis（TGA）and element analysis.Finally,in different elution mode of HPLC,we explored the chiral recognition ability of the CD-CSPs for various types of analytes.CSP 2 has good separation effect on Dan sulfonyl amino acids（Dns-amino acids）type samples,where the separation factor（α）of Dns-Thr and Dns-Aca can reach 2.86 and 1.97,which is better than the separation effect of single-charged cation CD-CSP（2）We also used the“thiol-ene”click chemistry reaction to build a bottom-up bridged cyclodextrin bilayer on the surface of silica gel to prepare a thioether-bridged natural cyclodextrin bilayer stationary phase（TIBCD-CSP）and the corresponding bottom and top layer of the single-layer natural CD-CSPS（MAICD-CSP and HMDCD-CSP）.TIBCD-CSP can separate twenty isoxazoline enantiomers,twelve of them can achieve baseline separation（R_S>1.5）,and for Dns-amino acids,all R_S are more than 3.1.By comparing the chiral recognition ability of the three CSPs to separate multiple enantiomers under the same conditions,the synergistic effect of the existence of two-layer CD cavity on chiral separation in double-layer bridge CD-CSP was investigated.（3）β-cyclodextrin covalent organic framework（β-CD COF）was prepared by the schiff base reaction of hepta-（6-amino-6-deoxy）-β-CD with terephthalaldehyde.We further used FT-IR,¹³C SSNMR,powder x-ray diffraction（PXRD）,TGA,scanning electron microscopy（SEM）,transmission electron microscopy（TEM）and nitrogen adsorption isotherm to prove thatβ-CD COF is a crystalline material composed of ordered accumulation of CD units.Finally,we explored various ways to prepareβ-CD COF as an appropriate column filler,including immobilization on the surface of silica gel or blending with silica gel,and applied it in the field of chromatographic chiral separation.It showed a certain chiral recognition ability for some flavanones（Flas）and isoxazoline enantiomers.更多还原