PREPARATIVE ELECTROPHORETIC CHIRAL SEPARATIONS

对映体的分离对制药工业的重要性是公认的。尽管在许多情况下，一种对映体具有预期的药理活性，而另一种对映体可能会产生不良的副作用，但人们经常忽略的一点是，在某些情况下，两种对映体都可能具有治疗价值……只是不同的疾病状态。因此，开发制备和半制备规模手性分离的经济方法是非常可取的，特别是对于研发环境，在开发更昂贵，效率较低的立体特异性合成策略之前，可能只需要少量材料就可以启动筛选。该项目的具体目标是解决这一关键需要的发展制备性手性分离。我们的方法是探索基于连续自由流动电泳的制备性手性分离方法，在缓冲液中使用硫酸环糊精作为手性添加剂。连续自由流动电泳在大规模水性手性分离中的应用是新颖的，有可能在水溶液中获得mg至g/小时的纯手性药物对映体，广泛适用于许多不同类别的手性药物以及手性中间体或代谢物。实验设计允许手性选择器（通常昂贵和/或稀有）的潜在回收和再利用，从而增加了该方法的经济吸引力。

It is well recognized that the separation of enantiomers is important to the pharmaceutical industry. Although much attention has been paid to the fact that in many cases, one enantiomer has the desired pharmacological activity whereas the other enantiomer may be responsible for undesirable side-effects, a point that often gets lost is that in some cases, both enantiomers may have therapeutic value...just not for the same disease state. Thus the development of economical methods for preparative and semipreparative scale chiral separations is highly desirable, particularly for an R and D setting, where only small amounts of material may be required to initiate screening prior to developing more costly, less efficient stereospecific synthetic strategies. The specific aim of the project is to address this critical need for the development of preparative chiral separations. Our approach is to explore preparative chiral separation methods based on continuous free flow electrophoresis using a sulfated cyclodextrin as the chiral additive in the buffer. The application of continuous free flow electrophoresis to bulk scale aqueous chiral separations is novel and has the potential for obtaining mg to g/hour quantities of both pure enantiomers of chiral drugs in aqueous solution, with wide applicability for a broad range of chiral drugs from many different categories as well as chiral intermediates or metabolites. The experimental design allows for the potential recovery and reuse of the chiral selector (typically expensive and/or rare), thereby increasing the economic appeal of this approach.