The natural product pestalone has been shown to have antibiotic activity against resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). However, pestalone is not readily isolated from its natural source, and its total synthesis has proven to be challenging due to low yielding reactions. Presented is the synthesis of 16 pestalone analogs, as well as the main carbon backbone. Attempts to synthesize the core structure of pestalone have proved difficult and are still in progress. The analogs were synthesized from either substituted benzaldehydes or phthalic anhydride using a Grignard reaction as the key step, with most yields between 65 and 85% for both reactions. The analogs were tested in bacterial assays against Gram-positive S. aureus and B. subtilis, as well as Gram-negative E. coli and P. aeruginosa, with 6 compounds showing antibiotic activity.
