Pestalone, a natural product that has been shown to have antibiotic properties, has demonstrated activity against antibiotic resistant bacteria, most notably Methicillin-resistant Staphylococcus aureus. Pestalone is difficult to isolate from a marine fungus, it’s natural source, and prior synthesis have been low yielding, although it has been potent against bacteria. This work explores the structure activity relationship of simplified Pestalone analogs that can be synthesized in 3-5 reactions. The overall yield for each synthesis is 65%-99%. So far, at least twelve analogs of Pestalone has been synthesized with a series of reactions using substituted benzaldehydes, 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 twelve 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.
