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Synthetic studies of the antimicrobial secondary metabolitethiomuracinA (1) were initiated to improve chemical stability andphysicochemical properties. Functional group modifications of 1included removing the C2–C7 side chain, derivatizingthe C84 epoxide region, and altering the C44 hydroxyphenylalaninemotif. The resulting derivatives simplified and stabilized the chemicalstructure and were evaluated for antibacterial activity relative to 1. The simplified structure and improved organic solubilityof the derivatives facilitated isolation yields from fermentationbroths and simplified the procedures involved for the process. Theseadvancements increased material supply for continued medicinal chemistryoptimization and culminated in the identification of 2, a structurally simplified and chemically stable analogue of 1which retained potent antibiotic activity. [ABSTRACT FROM AUTHOR]