Synthesis of Potential Small-Molecule Inhibitors for S. Commune Metacaspase
Abstract
This thesis explores using the Demkiw one-pot reaction as a robust method for the generation of potential inhibitors of metacaspases.. This reaction generates ketones from carboxylic acids and heteroaryl halides under mild conditions and is compatible with a wide range of starting materials to generate a diverse library of compounds. Compounds were synthesized to explore the scope of the reaction with a variety of starting materials. These reactions are important because eventually this method of synthesis will be used to generate different inhibitors that can interact with a class of metacaspases that our collaborators have been studying. The potential of these compounds to inhibit a series of metacaspases will be measured in the Fox lab. The most promising inhibitors may be used to generate a crystallized enzyme-inhibitor complex in order to obtain a structure using x-ray crystallography. Characterization of the metacaspase complex will enable a better understanding of its involvement in the cell death pathway of organisms. Optimized synthesis of four compounds and their characterization indicate that this method of synthesis is appropriate to generate a diverse library of potential inhibitors for this class of proteases.
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