Date of Award
Spring 5-3-2019
Document Type
Honors Project
Degree Name
Bachelor of Science
Department
Chemistry
Department Chair or Program Director
Sharpless, Charles
First Advisor
Oldham, Davis
Major or Concentration
Chemistry (ACS Certified)
Abstract
Tuberculosis is the leading cause of death from infectious disease in the world. Although tuberculosis drugs exist, the rise of 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 tuberculosis 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 vitro. In this research, nine derivatives of compound 1 were synthesized 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%. A silane reduction to remove the 4-hydroxy group was also explored but exhibited low yields. In future research, these derivatives will be tested in vitro to determine suitability for development as potential tuberculosis drugs.
Recommended Citation
Jones, Lindsey, "Synthesis of Piperidine-Based Inhibitors of KasA, a Vital Enzyme of M. tuberculosis" (2019). Student Research Submissions. 272.
https://scholar.umw.edu/student_research/272