N-Thiolated b-lactam antibiotics: Synthesis and structure-activity studies of C3 oxygenated derivatives and attachement to new, functionalized caprolactone monomers and polymers

• Main Author: Leslie, J Michelle
• Format: Others
• Published: Scholar Commons 2006
• Subjects: Penicillin; Vancomycin; MRSA; Bacillus; Polyester; American Studies; Arts and Humanities
• Online Access: http://scholarcommons.usf.edu/etd/2601; http://scholarcommons.usf.edu/cgi/viewcontent.cgi?article=3600&context=etd

N-Thiolated beta-lactams are a new class of anti-MRSA and anti-Bacillus agents that have recently been reported by our laboratories. From previous studies performed in our laboratories, it is believed that the N-thiolated beta-lactams exert their antimicrobial activity through a unique mode of action that is completely unlike that of classical beta-lactam antibiotics. In the first chapter of this dissertation, a review of previously prepared N-thiolated beta-lactam analogues and their mode of action is presented. In the second chapter, the synthesis of seven different C3-oxygenated derivatives is described. These analogues were tested for antibacterial activity against Staphylococcus aureus, nine different strains of MRSA, and seven different species of Bacillus. The results of the antibacterial testing will be discussed in relation to the differences in the structures of the analogues. In chapter 3, the design and synthesis of two new, functionalized caprolactone monomers are presented. FTSThese monomers were subsequently cooligomerized with epsilon-caprolactone, as described in chapter 4. N-thiolated beta-lactams were attached to the functionalized oligomers. These antibiotic containing oligomers were then screened for activity against MSSA, MRSA, and Bacillus. The results of these biological tests and their implications for future experiments are discussed.