The semisynthetic modification of the antibiotic enduracidin

The lipopetide antibiotic enduracidin has excellent bactericidal activity against many Gram-positive bacteria including vancomycin-resistant Enterococci sp. and methicillin-resistant S. aureus. Bacterial resistance to enduracidin has not been observed. Despite having high bioactivity, enduracidin's low solubility at neutral pH limits its viability for therapeutic use. New enduracidin analogs are needed to improve solubility. The lipid tail and five hydroxyphenylglycine (Hpg) residues were targeted for semisynthentic modification in this study. A series of analogs investigating the effects of incoporating charged groups derived from p-aminobenzoic acid and alkyl amines into the lipid tail were prepared. The Hpg groups were modified via nitration and subsequent reduction affording both nitro and amino enduracidin analogs. The preparation and characterization of these new enduracidin analogs will be presented.