Abstract

The 21st century has seen a dramatic acceleration in the evolution of bacterial resistance. Many classes of commercial antibiotics, including most current commercial β-lactams, were structurally optimized to counter 20th century pathogens. The carbapenems represent the most potent and broadest spectrum of the β-lactams, representing crucial last line agents to treat lifethreatening infections. While the 21st century has seen the appearance of carbapenem-resistant strains, the basic substitution pattern of commercial carbapenem antibiotics has remained constant, other than minor modifications at the C2 position. This research will investigate whether substitution at an atypical carbapenem position, the C5 position, can improve the antibiotic’s potency against resistant pathogens, particularly including Mycobacterium tuberculosis, Mycobacterium abscessus and Acinetobacter baumannii. This project produced improved synthetic methodology to generate this atypically substituted class of carbapenem, helped define the effect of substituents at this position on the carbapenemase susceptibility and binding to transpeptidase targets, and demonstrated that selected C5-substituted carbapenems can be superior to current commercial carbapenem antibiotics against clinically important pathogen.

Degree Date

Fall 12-15-2018

Document Type

Thesis

Degree Name

M.S.

Department

Chemistry

Advisor

John Buynak

Subject Area

Chemistry

Number of Pages

113

Format

pdf

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Available for download on Saturday, December 12, 2020

Share

COinS