Pulvinones were synthesized (> 180) in arrays and evaluated as inhibitors of early stage cell wall biosynthesis enzymes MurA–MurD. Several pulvinones inhibited Mur enzymes with IC50's in the 1–10μg/mL range and demonstrated antibacterial activity against Gram- positive bacteria including methicillin-resistant Staphyloccus aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae.