Chemical modification of fortimicins: preparation of 4-N-substituted fortimicin B.

Among the new aminoglycoside antibiotic family for fortimicins, components A, C and D have higher activity compared to their 4-N-deacylated components B and KE. Synthesis and antibacterial activities of 4-N-acyl- and 4-N-alkyl-fortimicin B derivatives are described. 4-N-Acylfortimicin B's, which are relatively unstable in alkaline conditions, were converted to stable 4-N-alkyl derivatives with diborane. The activity is greatly affected by the 4-N-substituents, and the presence of hydrophilic group(s) is necessary to confer activity on the derivatives. 4-N-(2-Aminoethyl)-, 4-N-(4-amino-2-hydroxybutyl)- and 4-N-(2-hydroxy-4-methylaminobutyl)-fortimicin B are the most potent compounds among them.