Date of Award


Document Type


Degree Name

Master of Science (MS)


Pharmaceutical Sciences

Research Advisor

Richard E. Lee, Ph.D.


John K. Buolamwini, Ph.D. Mark A. Miller, Ph.D.


Antibiotics, antimicrobials, pyrrolidine, tetramic


As bacterial infectious diseases are a major cause of morbity and mortality throughout the world, and many causative organisms are resistant to currently available antibiotics, the motivation for the development of new drugs is readily apparent. A number of natural products exhibiting antimicrobial activity possess a tetramic acid (2,4-pyrrolidinedione) functional group. As their antibacterial mechanism of action is different from that of many of the currently available antibiotics, these compounds have potential to serve as a basis for a pharmacophore in synthetic compounds. However, toxicity to eukaryotic cells is frequently a problem with currently known tetramic acids. The purpose of the project, as outlined in the following pages, is to demonstrate a method of synthesis of a small library of compounds containing the tetramic acid ring, and to illustrate their structure-activity relationship as agents both having activity against Gram-positive bacteria and possessing low hemolytic activity. Chapter One takes an overview of a number of the different classes of antibiotics available today, with emphasis on their method of action, then covers several naturally occurring tetramic acid compounds with antibiotic activity, and finally methods of synthesis. Chapter Two details the methods used to synthesize and characterize the set of compounds and examines their activity against a set of Gram-positive bacteria, with the purpose of clarifying their structure-activity relationship.