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Wednesday, April 26 • 8:30am - 10:00am
Development of a robust synthetic scheme to produce C9 analogs of the antibiotic pestalone.

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Pestalone is a natural product originally isolated in 2001 from a cofermentation of a marine fungus and bacterium. It has been synthesized by multiple groups including Nishiyama et al., Nikolay Slavov et al., and Ling Liu et al who found pestalone to have highly potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MIC = 37 ng/mL) and vancomycin-resistant Enterococcus faecium bacteria (MIC = 78 ng/mL). Unfortunately, this natural product can be rendered inactive due to an intramolecular cyclization between the C9 aldehyde and the bridging ketone forming a lactone. The goal of this project is to develop a reaction scheme to successfully produce pestalone analogs replacing the aldehyde with a range of electronic and steric functional groups to reduce the undesired reactivity while maintaining or improving antibacterial activity. Eighteen analogs were synthesized using a two step synthesis involving first a grignard addition of bromobenzene to a substituted phthalic anhydride(30-99% Yield) and then modifying the produced carboxylic acid through esterification(15-76% Yield) or amidation(7-93% Yield). These analogs were then subjected to a broth dilution minimum inhibitory concentration assay against Staphylococcus aureus and it was found that the analogs with the carboxylic acid only showed activity.


Wednesday April 26, 2017 8:30am - 10:00am PDT
Concourse - Wilma Sherrill Center