Synthesis and Evaluation of Novel 5-O-(4-C-Aminoalkyl-β-D-ribofuranosyl) Apramycin Derivatives for the Inhibition of Gram-Negative Pathogens Carrying the Aminoglycoside Phosphotransferase(3′)-Ia Resistance Determinant

We report the synthesis and evaluation of two new apramycin 5-O-β-d-ribofuranosides, or apralogs, carrying aminoalkyl branches at the ribofuranose 4-position. This novel modification conveys excellent activity for the inhibition of protein synthesis by wild-type bacterial ribosomes and correspondingly high antibacterial activity against several Gram-negative pathogens. Notably, these new modifications overcome the reduction of antibacterial activity in other 2-deoxystreptamine-type aminoglycosides carrying a 5-O-ribofuranosyl moiety when challenged by the presence of an aminoglycoside phosphotransferase enzyme capable of acting on the ribose 5-position.