Tuberculosis is the leading cause of death from infectious disease in the world. Although tuberculosis drugs exist, the rise of multidrug-resistant and extensively drug-resistant tuberculosis has created a need for new research. Identifying novel, effective drugs for treatment of tuberculosis could reduce the cost of care and treatment time, saving millions of lives. The enzyme KasA, which synthesizes part of the bacterial cell wall, has been identified as an attractive drug target. A virtual screen using KasA discovered a compound, 4-(4-bromophenyl)-1-pyrenemethyl-4-piperidinol (1), which inhibited bacterial growth. In this research, derivatives of compound 1 were created for future testing with live bacteria. A lithium-halogen exchange reaction was used to attempt to create a piperidinone-based derivative with varied substituents, but the method yields were low and difficult to purify. A Grignard process was also attempted with similar results. Alkylation of 4-substituted-4-piperidinols was successful in creating derivatives with arylmethyl substituents in yields from 51-85%. Additional derivatives will be made with changes in the aryl group of the piperidinol and N-alkyl groups. In future research, these derivatives will be tested <i>in vitro</i> to determine suitability for future tuberculosis drug research.

Synthesis of piperidinol-based inhibitors of KasA: A novel treatment for <i>Mycobacterium tuberculosis</i> infection

2019 Spring National Meeting

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Synthesis of piperidinol-based inhibitors of KasA: A novel treatment for Mycobacterium tuberculosis infection