The pharmacological activity of enantiomers of a chiral compound can be influenced to a great extent by molecular chiral recognition, the ability of a chiral biological system to discriminate between enantiomers. Typically one enantiomer will have better activity than its enantiomer. This difference in biological response generated by enantiomers upon binding to a biological target is a consequence of their differential interaction with the binding site. When designing new ligands for biological targets it is important to examine their constituent enantiomers. This dissertation is concerned with the synthesis of enantiomerically pure ring E analogs of methyllycaconitine and trans 4,5-disubstituted oxazolidinones in an effort to understand their interaction with their biological targets in a three-dimensional sense.
Due to their involvement in many physiological functions, nicotinic acetylcholine receptors (nAChRs) are important potential therapeutic targets for a large variety of neurodegenerative and psychiatric disorders. Ring E analogs of methyllycaconitine have been previously reported to act as noncompetitive antagonists of a subtype of nAChRs. In this dissertation, a new set of 20 compounds was prepared, consisting of enantiomers and various diastereomeric mixtures of three lead compounds from previously studied ring E analogs. The examination of the 3-D interaction of this set of compounds with the nAChRs leads to a better understanding of the formation of ligand-receptor complex and the structural demands required for a good binding.
A new class of antibacterial agents, the 4,5-disubstituted oxazolidinones, has been developed that exhibit inhibitory activity at the T box transcription antitermination system that controls the gene expression in many bacteria. In this dissertation, the enantiomers and the cis isomers of two lead compounds were prepared and used to study the effect of their chirality on the binding to the T box antiterminator. The biological results indicated that there is chiral recognition associated with the binding of 4,5-disubstituted oxazolidinones to the T box antiterminator.