Synthesis And Antiribosomal Activities Of 4 '-Omicron-, 6 '-Omicron-, 4 ''-Omicron-, 4 ',6 '-Omicron And 4 '',6 ''-Omicron-Derivatives In The Kanamycin Series Indicate Differing Target Selectivity Patterns Between The 4,5-And 4,6-Series Of Disubstituted 2-Deoxystreptamine Aminoglycoside Antibiotics

Chemistry for the efficient modification of the kanamycin class of 4,6-aminoglycosides at the 4'-position is presented. In all kanamycins but kanamycin B, 4'-Omicron-alkylation is strongly detrimental to antiribosomal and antibacterial activity. Ethylation of kanamycin B at the 4 ''-position entails little loss of antiribosomal and antibacterial activity, but no increase of ribosomal selectivity. These results are contrasted with those for the 4,5-aminoglycosides, where 4'-Omicron-alkylation of paromomycin causes only a minimal loss of activity but results in a significant increase in selectivity with a concomitant loss of ototoxicity.