481 SAR Side Chain Derivatives of the Antibiotic Cytosporone E

Friday, 23 October 2009: 1:45 PM
103-B (Puerto Rico Convention Center)
Erin M. Cartwright , Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC
Justin K. Wyatt , Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC

The novel antibiotic cytosporone E, a metabolite of the endophytic fungus Cytospora sp., shows weak antibacterial activity towards Gram-positive bacteria and is inactive against Gram-negative bacteria. Thus, to find a more potent antibiotic, we synthesized multiple derivatives of cytosporone E with changes in the side chain of the lactone. These derivatives were synthesized from N,N-diethyl-3,4,5-trimethoxybenzamide via ortho-alkylation of the aromatic ring with the appropriate aldehydes, followed by hydrolysis to afford the lactones. Finally, the methoxy groups were removed giving the corresponding cytosporone E derivatives. These synthetic derivatives will be assayed for a structure activity relationship (SAR) study using the Kirby-Bauer method; a few of our derivatives have been assayed. This is performed by aseptically placing filter paper disks containing each derivative onto heavily-inoculated plates of agar. The plates are then incubated overnight at 37 C affording the antibacterial results. Future derivatives will be synthesized using the findings of this SAR study to increase potency.