Synthesis, Antibacterial and Antiribosomal Activity of the 3C-Aminoalkyl Modification in the Ribofuranosyl Ring of Apralogs (5-O-Ribofuranosyl Apramycins)

The synthesis and antiribosomal and antibacterial activity of both anomers of a novel apralog, 5-O-(5-amino-3-C-dimethylaminopropyl-D-ribofuranosyl)apramycin, are reported. Both anomers show excellent activity for the inhibition of bacterial ribosomes and that of MRSA and various wild-type Gram negative pathogens. The new compounds retain activity in the presence of the aminoglycoside phosphoryltransferase aminoglycoside modifying enzymes that act on the primary hydroxy group of typical 4,5-(2-deoxystreptamine)-type aminoglycoside and related apramycin derivatives. Unexpectedly, the two anomers have comparable activity both for the inhibition of bacterial ribosomes and of the various bacterial strains tested.

Automated summary

The synthesis, antiribosomal, and antibacterial activity of two anomers of a novel apralog, 5-O-(5-amino-3-C-dimethylaminopropyl-D-ribofuranosyl)apramycin, were studied. Both anomers showed strong activity against bacterial ribosomes, MRSA, and various wild-type Gram-negative pathogens. These compounds were also found to be effective against aminoglycoside modifying enzymes, enabling them to retain their activity in the presence of these enzymes. Surprisingly, the two anomers exhibited comparable activity against bacterial ribosomes and the tested bacterial strains.