【作者】 杨艳霞；

【导师】 蒋新宇；

【作者基本信息】 中南大学 ， 分析化学， 2012， 硕士

【摘要】 随着对手性分子认识的不断深入,人们对单一手性物质的需求量越来越大。获得单一手性物质的方法也已成为当前研究的热点。目前获得单一手性物质的方法大致可以分为三种：①手性源合成法,②不对称合成法,③外消旋体拆分法。其中,手性配体交换色谱法是一种简便有效且应用广泛的分离手段和准确测定对映体纯度的分析方法。手性配体交换色谱按照手性选择体的存在形式可分为手性配体交换流动相法和手性配体交换固定相法。手性配体交换流动相法的优点是可以采用普通的非手性柱,分析成本低；通过改变手性选择体的种类、浓度及流动相组成而优化分离条件,还可通过改变手性选择体的绝对构型来改变对映体的出峰顺序。本论文以脯氨酸类手性离子液体作为手性选择体,运用配体交换色谱流动相法拆分色氨酸、扁桃酸、邻氯扁桃酸对映体,考察了拆分过程中的影响因素,如手性离子液体的烷基链长,金属离子和配体的浓度,流动相的pH值等。并从热力学角度对其拆分过程进行了探讨。基于配体交换的机理,研究了脯氨酸手性离子液体作为流动相添加剂,在C18柱上拆分色氨酸(tryptophan, Trp)对映体的方法及其热力学过程。得出色氨酸的最优分离条件为：4mmol/L [C6mim][Pro]、8mmol/L CuSO4溶液和甲醇体的体积比为80：20,pH4.00,流速1.0mL/min,温度为25℃。在此条件下,色氨酸对映体可以成功分离。通过对色氨酸对映体的拆分过程进行热力学分析,表明：该拆分过程是一个放热的焓控过程。基于配体交换的机理,研究了脯氨酸手性离子液体作为流动相添加剂,在C18柱上拆分扁桃酸(mandelic acid, MA)对映体的方法及其热力学过程。在最优条件下,扁桃酸对映体的分离因子为1.22,分离度可达2.24。并且测定了拆分过程中的一些热力学参数,结果表明MA对映体的拆分过程为放热的焓控过程。测得L-构型MA的AH0比D-构型的小,这说明L-构型比D-构型更难洗脱,L-MA和固定相有更强的相互作用,保留时间更长。基于配体交换的机理,研究了脯氨酸手性离子液体作为流动相添加剂,在C18柱上拆分邻氯扁桃酸(o-chloro mandelic acid,O-Cl-MA)对映体的方法及其热力学过程。邻氯扁桃酸拆分的最佳条件为：6mmol/L [C4mim][Pro]、8mmol/L CuSO4溶液和甲醇体的积比为85：15,pH5.10,流速0.9mL/min,温度为25℃。在此条件下,邻氯扁桃酸对映体可以基线分离。通过对邻氯扁桃酸对映体的拆分过程进行热力学分析,表明：该拆分过程是一个放热的焓控过程。更多还原

【Abstract】 There is an increasing demand for optically pure enantiomers in the chemical industry, which can be attributed largely to a heightened awareness that enantiomers of a racemic drug usually display markedly different pharmacological activities. Different methods are used to obtain enantiomeric purity, such as, synthesis from chiral pool, the asymmetric synthesis and chiral separation. Chiral ligand exchange chromatography is not only an analysis method of determination of enantiomeric purity accurately but also is especially effective for the separation of enantiomers. Chiral ligand exchange chromatography includes enantiomeric separations on chiral stationary (CSP) and chiral mobile phase (CMP)-type separations. The latter using a common non chiral column is low cost. To optimize the conditions of separation, we can change the type, concentration of the chiral selector and composition of mobile phase. When the absolute configuration of chiral selector is changed, the elute order of enantiomers is also changed.In this paper, the resolutions of tryptophan enantiomers(Trp), mandelic acid enantiomers (MA), and o-chloro-mandelic acid enantiomes (0-Cl-MA) by ligand exchange chromatography were completed on a C18column with the chiral ionic liquids containing imidazolium cations and L-proline anions ([Cnmim][Pro]) as chiral selectors. Some factors influencing resolution, such as alkyl chain length of ILs, concentrations of Cu2+and [Cnmim][Pro], and pH of the mobile phase, were investigated. And its thermodynamical process was studied.Based on ligand exchange mechanism, Trp enantiomers were successfully separated using [C6mim][Pro] as a chiral ligand coordinated with copper(Ⅱ). Separation conditions were optimized, where4mmol/L [C6mim][Pro] and8mmol/L Cu2+were dissolved in methanol/water (20:80, v/v) with pH4.00at a flow rate of1.0mL/min. Under this condition, the Trp enantiomers could be baseline separated and the separation factor and resolution were1.25and2.30, respectively. In the range of25℃-45℃, the values of△△H0and△△S0ere both negative, and|△△H0>|T△△S0|, which showed that the chiral separation of Trp enantiomers was an enthalpy-controlled process.Based on ligand exchange mechanism, MA enantiomers were successfully separated using [C4mim][Pro] as a chiral ligand coordinated with copper(Ⅱ). Under the optimal conditions, the separation of the two enantiomers was obtained with enantioseparation factor of1.22and resolution of2.24. And some thermodynamical parameters were evaluated. In the range of25℃-45℃, the values of△△H0and△△S0were both negative, and|△△H0|>|T△△S0|, which showed that the chiral separation of MA enantiomers was an enthalpy-controlled process. And the values of AH0of D-MA were larger than those of L-MA, indicating that L-MA had stronger affinity to the stationary phase, which is consistent with the elution order of monomers.Based on ligand exchange mechanism, O-C1-MA enantiomers were successfully separated using [C4mim][Pro] as a chiral ligand coordinated with copper(Ⅱ). Separation conditions were optimized, where4mmol/L [C4mim][Pro] and8mmol/L Cu2+were dissolved in methanol/water (15:85, v/v) with pH5.10at a flow rate of0.9mL/min. Under this condition, the O-Cl-MA enantiomers could be baseline separated. In the range of25℃-45℃, the values of△△H0and△△S0were both negative, and|△△H0|>|△△S0|, which showed that the chiral separation of O-Cl-MA enantiomers was an enthalpy-controlled process.更多还原