The World Health Organization has recently described antibiotic resistance as a significant threat to global public health. A possible solution to the growth in resistance is through the development of new drugs with unique structures. Since 1981, nearly half of FDA approved drugs were influenced by the novel structures of natural products. Acremostrictin is a natural product that was isolated from a marine fungus and found to have weak antibacterial qualities and a novel carbon structure. However, no synthesis has been reported to date. Through development of the synthesis of acremostrictin, access to analogs - compounds with similar structures but minute specific differences - will be feasible. We designed an epoxide analog called epoxyacremostrictin, which could display potentially stronger antimicrobial activity than acremostrictin due to its electrophilic character. This work focuses on two approaches for the synthesis of the starting material, 2-iodo-5-methylcyclopentenone, required to produce these analogs. The first strategy relies on the direct addition of an iodine and a methyl group to cyclopentenone. Promising reaction conditions for addition of the iodine were identified using a four-hour reaction time followed by column chromatography to provide the iodinated product in high purity and yield, which was confirmed by nuclear magnetic resonance (NMR) spectroscopy. The original approach to add the methyl group proved to be problematic due to the presence of the enone moiety, so we turned to an alternative strategy. This second route uses a Nazarov cyclization to install the methyl group and create the enone, which can then undergo iodination. The Nazarov cyclization stalled at room temperature, as observed in NMR, but may have promise with modifications to the reaction
