Chemical modification of amikacin at C-4'' with inversion of configuration.

Sir: With the appearance of an aminoglycoside 4', 4"-nucleotidyl transferase,') selective modification of the clinical important amikacin (1) at these positions became of interest. Although enzymatic deactivation involving hydroxyl groups usually is overcome by "deoxygenation' 1,2) our efforts are focussed on the introduction of a substituent, which lacks ability to participate in a resistance mechanism but preserves the original polarity. At this time we wish to report on the synthesis and antibacterial activity of 4"-azido-4"-deoxy4"-epi-amikacin (13) and 4"-deoxy-4"-fluoro-4"epi-amikacin (14). To trace the effect of the configurational change itself as well as that of fluorination, 4"-epi-amikacin (15) and 6"-deoxy6"-fluoroamikacin (9) were also prepared. Starting from 1, protection of the amino functions with the tent-butoxycarbonyl (Boc) group by reaction with di-tert-butyl dicarbonate in DMSO H_O (95: 5) for 6 hours at 60°C gave 3,6',3",4"'-tetra-N-Boc-amikacin3' (2) in 96 yield. Its treatment with chi orotriphenylmethane