Vancomycin prodrug (compound 13c) is a prodrug of Vancomycin. It exhibits antibacterial activity against Staphylococcus aureus (S. aureus) 330041, methicillin-resistant Staphylococcus aureus (MRSA) USA 300, and MRSA 3390, with minimum inhibitory concentrations (MICs) of 0.78 μM, 0.78 μM, and 1.56 μM, respectively. This prodrug can rapidly bind to the Cys-34 residue in plasma. It demonstrates therapeutic efficacy in mice infected with MRSA USA300, comparable to Vancomycin. As an albumin-binding, acid-sensitive prodrug, Vancomycin prodrug maintains Vancomycin's effectiveness against gram-positive bacterial infections while significantly reducing nephrotoxicity.