新型咪唑二甲酰胺基桥联双β-环糊精手性液相色谱键合相制备与评价

Preparation and evaluation of a novel imidazolediamide bridged bis(β-cyclodextrin)-bonded chiral stationary phase for HPLC

基于咪唑-4,5-二甲酸与6-氨基-β-环糊精的缩合反应,合成一种桥联双环糊精并将其键合到硅胶表面,制备一种新型的咪唑二甲酰胺基桥联双β-环糊精手性固定相(IMCDP)。经化学结构表征后,采用氨基酸和β-阻滞剂等极性化合物作探针,评价新固定相在反相和极性有机模式下的手性液相色谱性能,同时与普通环糊精固定相(CDCSP)进行性能比较。结果表明,IMCDP能较好地拆分42种手性物质,包括33种天然氨基酸和9种β-阻滞剂类药物,其中丹磺酰化亮氨酸(DNS-LEU)、丹磺酰化苯丙氨酸(DNS-PHE)、异硫氰酸苯酯化脯氨酸(PITC-PRO)、2,4-二硝基苯基化赖氨酸(DNP-LYS)以及美托洛尔(Metoprolol)对映体的分离度(Rs)分别达到2.76,2.87,2.01,3.01和1.62。桥联环糊精上邻近的2个空腔的协同包结作用,以及咪唑二甲酰胺桥基提供的氢键、π-π,以及类似吡咯和吡啶的酸碱性位点增强了IMCDP的手性分离能力。这种无需端口衍生化的新型桥联环糊精固定相可用于拆分氨基酸及其类似结构的手性药物。

Based on the condensation reaction of imidazole-4,5-dicarboxylic acid and 6-amino-β-cyclodextrin,a new type of bridged cyclodextrin was firstly synthesized and bonded onto the surface of silica gel to obtain an imidazolediamide bridged bis(β-cyclodextrin)-bonded chiral stationary phase(IMCDP).After chemical structure characterization,a series of polar compounds such as amino acids andβ-blockers were used as probes to respectively evaluate the chiral liquid chromatography performance of the new stationary phase in reversedphase and polar organic modes,and compared with that of the common cyclodextrin stationary phase(CDCSP).The results showed that IMCDP could well resolve 42 kinds of chiral substances,including 33 natural amino acids and 9β-blocker drugs.The resolutions(Rs)of dansyl leucine(DNS-LEU),dansyl phenylalanine(DNSPHE),phenyl isothiocyanated proline(PITC-PRO),2,4-dinitrophenyl lysine(DNP-LYS)and metoprolol reached 2.76,2.87,2.01,3.01 and 1.62,respectively,which had the advantages of short separation time and high separation efficiency.These chiral compounds were highly polar and easy to ionize,although common cyclodextrins stationary phases could resolve these analytes,the variety was very limited.The synergistic inclusion of two adjacent cavities on the bridged cyclodextrin,as well as hydrogen bonding,π-π,and acid-basic sites like pyrrole and pyridine provided by the imidazole diamide bridging group may enhance the chiral separation ability of IMCDP.This new bridged cyclodextrin stationary phase,which does not need port derivatization,has an application prospect in the resolutions of amino acids and chiral drugs with similar structures.