Synthesis and antifungal activities of pradimicin derivatives, modification at C4'-position

The 4'-N-alkyl(1 approximately 10) and 4'-N-acyl derivatives (11 approximately 21) of pradimicins (PRMs) were synthesized by trimethylsilylation of PRMs A, C and FA-1 followed by condensation with appropriate alkylating and acylating agents. The 4'-hydroxy derivatives (23 and 24) were synthesized from PRM FA-2 in a 3-step sequence. Among these compounds, the 4'-N-carboxyl substituted alkyl (1, 5, 8 and 10), 4'-N-formyl (11) and 4'-axial-hydroxy (23) derivatives retained the antifungal activity of the parent compounds and showed great improvement in water solubility.