By Devda Nair, Rachel Rios

Faculty Mentor: Davis Oldham

Abstract

Tuberculosis is a major global health problem, and new compounds are needed to treat drug-resistant strains. One target for new drugs is the KasA enzyme, which is involved in bacterial cell wall synthesis. The goal of this project was to synthesize an analogue of a lead compound predicted to inhibit the KasA enzyme. The synthesis was carried out in four steps using standard organic chemistry reactions. A Grignard reagent was first prepared from 1,4-dibromobenzene and magnesium in diethyl ether and then reacted with N-Boc-4-piperidinone to form a tertiary alcohol through nucleophilic addition to the carbonyl group. The Boc protecting group was then removed using saturated ammonium chloride and ethyl acetate through extraction to isolate the free amine. The benzyl alcohol intermediate was converted to the corresponding benzyl chloride using thionyl chloride, and this intermediate was then reacted with the piperidine amine in the presence of potassium carbonate and potassium iodide under reflux conditions to form the final product. The reactions produced the target compound. This synthesis shows that reactions like Grignard additions, protecting group removal, and substitution can be used together to build more complex molecules that could be useful as KasA inhibitor analogues.