High Resolution of Chiral Compounds Using Protein-Multilayered Porous Membranes

手性分离是生产高效、安全药物的关键技术。目前用于拆分外消旋化合物的方法主要有选择结晶法和手性层析法，后者的用途更广，因为手性配体可以固定在载体上。我们描述了一种牛血清白蛋白(BSA)多层吸附的中空纤维膜作为固定相，实现了高分辨率和高速率的手性分离。通过辐射引发接枝聚合，将含环氧基团的接枝链均匀固定在多孔中空纤维膜的表面。随后，二乙氨基作为阴离子交换基团被引入到接枝链中，由于相互静电斥力，使接枝链向孔内扩张。扩展的聚合物链为牛血清白蛋白作为手性选择剂提供了多层结合部位。四种特定识别的L-色氨酸的多层结合程度的牛血清白蛋白，在流动相(Tris-HCl缓冲液)通过牛血清白蛋白多层多孔膜时，分离系数为6.6。此外，分离因子与流动相的流速无关，因为色氨酸对多层BSA的扩散传质阻力可以忽略不计。

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.