Synthesis and biological activity of 1-N-(4-(substituted)amidino and guanidino-2-hydroxybutyryl)kanamycins A and B

The synthesis and biological properties of 1-N-(4-(substituted)amidino and guanidino-2-hydroxybutyryl)kanamycins A and B are described. Reaction of 3,3'',6'-tri-N-tert-butoxycarbonyl-amikacin with an appropriate amidinating or guanidinating reagent and subsequent deblocking gave a series of amikacin derivatives having an amidino or guanidino group on the 4'''-position. The corresponding kanamycin B analogs were also prepared by a similar procedure. Among these derivatives, 1-N-(4-formamidino- and guanidino-2-hydroxybutyryl)kanamycins A and B exhibited antibacterial activity similar to the corresponding 4-amino analogs. The nephrotoxic potential of selected compounds is also briefly discussed.