Tobramycin analogues with C-5 aminoalkyl ether chains intended to mimic rings III and IV of paromomycin

Based on available X-ray structural and modeling data, a series of tobramycin derivatives with C-5 ether chains bearing basic groups were synthesized. These were intended to be hybrid molecules that combine features of tobramycin and paromomycin. Their binding to ribosomes and their antibacterial activity were determined. The 5-O-(2-guanidylethyl) ether of tobramycin (9g) was the most active analogue in the series. (C) 2003 Elsevier Science Ltd. All rights reserved.