High Resolution of Chiral Compounds Using Protein-Multilayered Porous Membranes

手性分离是生产安全有效药物的关键技术。目前，选择性结晶和手性色谱用于拆分各种外消旋化合物，后者是更通用的，因为手性配体可以固定在支持matrix.We描述了牛血清白蛋白（BSA）的多层吸附多孔中空纤维膜作为固定相，使手性分离在高分辨率和高速率。含环氧基团的接枝链通过辐射诱导接枝聚合均匀地固定在多孔中空纤维膜的孔的表面上。随后，作为阴离子交换部分的二乙基氨基基团被引入到接枝链中，这导致链由于相互静电排斥而向孔的内部扩展。扩展的聚合物链为BSA作为手性选择剂提供了多层结合位点。BSA与四种特异性识别的L-色氨酸的多层结合程度，在通过移动的流动相（Tris-HCl缓冲液）渗透期间分离因子为6.6，流动相（Tris-HCl缓冲液）通过BSA-多层多孔膜注入DL-色氨酸的外消旋溶液。此外，分离因子是恒定的，无论流速的移动的相，因为可以忽略不计的扩散传质阻力的色氨酸BSA多层的接枝链。

Chiral separation is an essential technology for producing effective and safe pharmaceuticals. At present, selective crystallization and chiral chromatography are used to resolve various racemic chemicals ; the latter is more versatile in that the chiral ligands can be immobilized on supporting matrices.We describe a bovine serum albumin (BSA)-multilayer-adsorbed porous hollow-fiber membrane as a stationary phase that enables chiral separations at a high resolution and high rate. Epoxy-group-containing graft chains were uniformly immobilized on the surface of pores throughout a porous hollow-fiber membrane by radiation-induced graft polymerization. Subsequently, a diethylamino group as an anion-exchange moiety was introduced to the graft chains, which caused the chains to expand toward the interior of the pores due to mutual electrostatic repulsion. The expanding polymer chains provided multilayer binding sites for BSA as a chiral selector. BSA with a degree of multilayer binding of four specifically recognized L-tryptophan with a separation factor of 6.6 during permeation by a mobile phase (Tris-HCl buffer) injected with a racemic solution of DL-tryptophan through the BSA-multilayered porous membrane. In addition, the separation factor was constant irrespective of flow rates of the mobile phase because of negligible diffusional mass-transfer resistance of tryptophan to BSA multilayered by the graft chains.