Pestalone, a natural product that has been shown to have antibiotic properties, has demonstrated activity against methicillin-resistant Staphylococcus aureus (MRSA) and other resistant bacteria. Although it is potent, Pestalone is difficult to isolate from a marine fungus, it’s natural source, and prior synthesis have been low yielding. This work investigates the structure activity relationship of simplified analogs of Pestalone that can be synthesized in 3-5 reactions. The overall yield for each 3-5 step synthesis is 65%-99%. Eight analogs of Pestalone has been synthesized with a series of reactions using substituted benzaldehydes or phthalic anhydride, with Grignard reactions being an important step in each reaction. These analogs were tested in bacterial cell death assays against Gram-positive S. aureus and Gram-negative E. coli. Two of the eight synthesized analogs demonstrated moderate activity against E. coli and one of the synthesized analogs showed activity against Staphylococcus aureus. These three analogs that showed activity will be used in a synthesis that would add a carbon chain to the analogs.
