Undergraduate Honors Theses

Thesis Defended

Spring 2017

Document Type


Type of Thesis

Departmental Honors


Chemistry & Biochemistry

First Advisor

Dr. Xiang Wang

Second Advisor

Dr. Joseph Falke

Third Advisor

Dr. James Orth


The issue of antibiotic resistance is not being solved by current efforts to discover new classes of antibiotics. In an attempt to combat this issue our lab has created a series of resistance-modifying agents (RMAs) based on natural indole alkaloids, which have been used to treat many different diseases. Through structure-activity relationship (SAR) studies, we have been optimizing tetracyclic indoline compounds that potentiate β-lactam antibiotics against methicillin-resistant Staphylococcus aureus (MRSA), but do not exhibit antibacterial activity on their own. This is important as it reduces selective pressures for resistance while allowing us to utilize previously obsolete antibiotic classes in the fight against resistant bacteria. In previous SAR studies done by the Wang Lab, a potent compound, 6a, was discovered as a potent lead compound. Additionally, the absolute stereochemistry of the tetracyclic ring structure was found to be essential to this class of RMAs. The research in this study focuses on synthesizing novel analogs from commercially available building blocks. It was determined that the addition of an ester group to the D-ring could not be tolerated; however a primary alcohol group can. This research also supports previous studies that have optimized the carbamate functional group on the D-ring of this tetracyclic scaffold.