PREPARATIVE ELECTROPHORETIC CHIRAL SEPARATIONS

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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.