SYNTHESIS OF 2"-AMINO-2"-DEOXYARBEKACIN AND ITS ANALOGS HAVING POTENT ACTIVITY AGAINST METHICILLIN-RESISTANT Staphylococcus aureus

Abstract

Based on our studies on the enzymatic modifications of arbekacin by methicillin-resistant Staphylococcus aureus (MRSA), replacement of the 2"-hydroxyl group by an amino group in arbekacin was designed to synthesize derivatives that would be active against MRSA. 2"-Amino-2"-deoxyarbekacin and five analogs were synthesized starting from dibekacin. Among them, 2"-amino-2"-deoxyarbekacin and the 5-epiamino analog showed excellent antibacterial activities against not only MRSA but also Gram-negative bacteria including Pseudomonas, and lower toxicities than arbekacin.