PREPARATIVE ELECTROPHORETIC CHIRAL SEPARATIONS

众所周知，对映体的分离对于制药工业是重要的。 尽管在许多情况下，一种对映体具有所需的药理活性，而另一种对映体可能导致不良副作用，但经常丢失的一点是，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，非常需要开发用于制备和半制备规模手性分离的经济方法，特别是对于R和D设置，其中在开发更昂贵、效率较低的立体特异性合成策略之前，可能仅需要少量的材料来启动筛选。该项目的具体目标是解决制备手性分离发展的这一关键需求。 我们的方法是探索基于连续自由流动电泳的制备型手性分离方法，使用硫酸化环糊精作为手性添加剂在缓冲液中。 连续自由流电泳在大规模水溶液手性分离中的应用是新颖的，并且具有在水溶液中获得mg至g/小时量的手性药物的两种纯对映异构体的潜力，对于来自许多不同类别的宽范围的手性药物以及手性中间体或代谢物具有广泛的适用性。 实验设计允许手性选择剂（通常昂贵和/或稀有）的潜在回收和再利用，从而增加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.