Chromatographic purification of quaternary ammonium compounds and combinatorial methods to determine selectors for chiral chromatography

This work is a culmination of research in two distinct areas of liquid chromatography: the analysis and purification of quaternary ammonium compounds using liquid chromatographic techniques, and the determination of enantioselective ligands for chiral liquid chromatography using combinatorial library methods.; With respect to the chromatographic purification of quaternary ammonium compounds, two projects are discussed. A facile, preparative-scale purification method for quaternary ammonium compounds (QACs) using normal-phase ion-pair chromatography encompasses the first project. The second project demonstrates the systematic study of mobile phase additives containing different cations (or analogue ions) using high performance liquid chromatography (HPLC) to show that the choice of mobile phase additive cation is important for the efficient elution of QACs.; The second research area involves the application of combinatorial libraries to{09}the determination of enantioselective ligands for chiral chromatography. Chiral selector development for chromatographic purposes has largely been empirical in nature. One suggests a compound which may exhibit chiral selectivity, synthesizes it, attaches it to a suitable solid support, and assesses it chromatographically using the racemic analyte of interest. Combinatorial libraries allow for the synthesis and screening of a much larger array of potential chiral selectors within a similar timeframe, thereby increasing the likelihood of finding one or more chiral selectors for a given racemic analyte.; Two projects have been developed for the application of combinatorial libraries for chiral selector determination. One project involves the application of mixture combinatorial libraries to accomplish this goal. Liquid chromatography-mass spectrometry (LC-MS) is employed to facilitate identification of selective library members and assess library purity. The second project demonstrates the use of parallel combinatorial libraries for the same purpose. In this case, library members are attached to solid phase synthesis resin and screened individually with the racemic analyte of interest using high throughput analytical techniques. In both cases, any lead compounds are synthesized in larger quantities, attached to silica gel, packed into HPLC columns, and assessed for chiral separation of the analyte.