Decagram-Scale Synthesis of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284

Medicinal chemistry efforts identified OSUAB-0284 (<b>2</b>) as a preclinical candidate to treat staphylococcal infections, especially those caused by methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Herein, we describe a fit-for-purpose route that enabled the production of >20 g of API for toxicology studies and further preclinical characterization. Process improvements include a 16-fold increase in yield over the longest sequence, a 21-fold increase in efficiency for the cost-limiting reagent, and reduction of chromatography to one silica plug across an 18-step route.