侧链带有手性氨基酸衍生物的螺旋聚苯乙炔手性固定相的设计合成与手性识别能力研究

In this project, novel helical poly(phenylacetylene)s as chiral stationary phases (CSPs) were synthesized, their chiral recognition abilities were evaluated, and the chiral recongition mechanism of three-aspect cooperation of chemical structures at side chains, main chain helical conformation, and intermolecular interaction was also investigated. First, chiral amino acid derivatives functionalized optically active phenylacetylene monomers and a phenylacetylene comonomer with a triethoxysilyl group were designed and synthesized via Sonagashira coupling reaction, elimination reaction, esterification reaction, amidation reaction, and the reaction of isocyanate with hydroxyl group. Then homopolymerization of the optically active phenylacetylene monomers and their copolymerization with the comonomers were carried out by using rhodium catalyst to synthesize dynamic helical poly(phenylacetylene) homopolymers and copolymers. Novel coated-type and immobilized-type poly(phenylacetylene)-based CSPs were prepared on the basic of investigating chiroptical properties of the polymers. During the stucture design of polymers, chiral side chains and the groups which are facile to form molecular interaction were introduced. Chiral recognition ability was optimized not only by the stucture design of polymers, but also by the adjustment of coating solvents and chromotography resolution conditions. Moreover chiral recongition mechanism was discussed. Especially, we put forward a new immobilization methodology for synthetic polymer-based CSPs, the immobilization reaction was carried out via intermolecular polycondensation of triethoxysilyl groups of copolymers so that the polymer network could be formed on silica gel surface and the efficient immobilization of polymers on silica gel was achieved. These series of helical poly(phenylacetylene)-based CSPs showed high chiral recognition abilities, and problems of the limited use of mobile phase were solved.This project will not only promote the developtment of novel CSPs, but also become a experimental and theoretical foundation to the improvement of chiral recognition abilities of CSPs.

本项目旨在合成新型螺旋聚苯乙炔手性固定相，评价其手性识别能力，揭示侧链化学结构、主链螺旋构象以及分子间作用力三方面协同作用的手性识别机制。首先设计合成手性氨基酸衍生化的光学活性苯乙炔单体及含有三乙氧基硅基的苯乙炔共聚单体。在铑系催化剂作用下，实现光学活性苯乙炔单体的均聚及其与共聚单体的共聚，合成动态螺旋聚苯乙炔均聚物和共聚物，在研究手性光学活性的基础上制备涂覆型和键合型手性固定相。通过在螺旋聚苯乙炔侧链中引入手性基团及易于形成分子间作用力的基团、改变涂敷溶剂和色谱条件等优化手性识别能力，揭示手性识别机制。提出新型键合方法，利用共聚物分子间三乙氧基硅基的缩合反应在硅胶表面交联而形成网状结构，实现在硅胶表面的固定。该系列螺旋聚苯乙炔手性固定相具有良好手性识别能力，且键合型手性固定相解决了流动相使用受限的问题。本项目将促进手性固定相新品种的开发，为提高手性固定相的手性识别能力奠定实验和理论基础。

手性与人们的健康和日常生活密切相关，多数药物存在手性结构，手性药物在生物体内的作用机理与它和体内靶分子之间的手性匹配和分子识别能力有关，手性药物对映体具有不同的生理活性、药理作用和毒副作用。对映体的识别与拆分对于生命科学和药物化学研究以及人类的健康具有十分重要的意义。高效液相色谱法（HPLC）以其操作简单、条件温和等优点，被公认为是对映体拆分最有效的手段之一，手性固定相材料的设计与发展是能否有效实现光学对映体的手性识别和拆分的关键技术，同时也是HPLC手性拆分技术的核心内容。本项目设计合成多个系列的手性氨基酸衍生化的光学活性苯乙炔新单体（以酰胺基为链接基团的带有氨基酸乙酯的系列光学活性苯乙炔新单体，以酰胺基为链接基团的带有氨基醇及其苯基氨基甲酸酯衍生物的系列光学活性苯乙炔新单体，以脲基为链接基团的光学活性苯乙炔新单体）及含有三乙氧基硅基的苯乙炔共聚单体。在铑系催化剂作用下，实现光学活性苯乙炔单体的均聚及其与共聚单体的共聚，合成动态螺旋聚苯乙炔均聚物和共聚物，在研究手性光学活性的基础上制备涂敷型和键合型手性固定相。本项目提出了新型键合方法，利用共聚物分子间三乙氧基硅基的缩合反应在硅胶表面交联而形成网状结构，实现在硅胶表面的键合。通过在螺旋聚苯乙炔侧链中引入手性基团及易于形成分子间作用力的基团、改变涂敷溶剂和色谱条件等优化手性识别能力，探讨该系列手性固定相的手性识别机制。所制备的手性固定相具有良好的手性识别能力，对于某些对映体的拆分达到甚至超过了多糖类商品手性固定相，且键合型手性固定相解决了流动相使用受限的问题。本项目开发的螺旋聚苯乙炔手性固定相是合成高分子手性固定相的新突破，尤其是键合型手性固定相的制备方法为合成聚合物手性固定相键合技术提供了新思路。本项目的研究促进了手性固定相新品种的开发，提高了手性固定相的手性识别能力，为扩大手性固定相的手性拆分范围奠定实验和理论基础。