The majority of the work in this dissertation presents a new synthetic methodology to synthesize an imidazoline from either a chiral or a racemic aziridine. The purpose of synthesizing imidazolines is for their known biological activity. Previous research in the Tepe group has developed a method to diastereoselectively synthesize racemic imidazolines from the trimethyl silyl chloride mediated cycloaddition of imines with azlactones. This methodology allowed access to a variety of imidazolines that have been shown to inhibit NF-κB mediated gene transcription. NF-κB is a nuclear transcription factor of of activated B cells found in almost all animal cell types. It is a protein complex that binds to certain DNA sequences and controls the transcription of genes. An SAR study has been conducted in our research group on this class of compounds. The ability of the imidazolines to inhibit NF-κB mediated gene transcription was measured by an assay on human cervical epithelial (HeLa) cells and human whole blood. The results of these studies have determined which functional groups were essential for efficient inhibition of NF-κB. These studies have also determined that one imidazoline enantiomer was a much more potent inhibitor than the other. Although our research group had created a diastereoselective method to synthesize imidazolines, there was still not a method to synthesize chiral imidazolines. Due to the cost, time, and inefficiencies of separation of racemic imidazolines by chiral HPLC or by other resolution methods an enantioselective method was needed. This thesis represents the progress towards an enantioselective synthesis of imidazolines. New synthetic methodologies to access an oxazolidin-2-one and an amino alcohol has been developed. In addition progress toward new synthetic methodologies to access guanidine heterocycles and diamines will also be discussed.
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