Abstract

Antibiotic resistance is one of the largest public health issues today. One way that antibiotic resistance can be prevented is through the introduction of novel antibiotics. Pestalone, a natural product derived from a deep-sea marine bacterium, has demonstrated activity against antibiotic resistant bacteria, most notably Methicillin-resistant Staphylococcus aureus. Pestalone is difficult to isolate from its natural source and prior synthesis have been low yielding, although it has been potent against bacteria. This work explores the structure activity relationship of a number of simplified Pestalone analogs that can be synthesized in 3-5 reactions with an overall yield for each synthesis of 65%-99%. Previously, 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. Recently, two additional analogs have been synthesized using this method and evaluated for their antibiotic activity. All synthesized 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. Active analogs will be used in a synthesis that would add a carbon chain to the analogs.

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