Antifungal activities of pradimicin derivatives modified at C4'-amino group

In order to explore potent derivatives of pradimicins (PRMs), modification of their C4'-amino group was carried out. 4'-N-Cyano (1,2), 4'-deamino-4'-nitroguanidino (4), 4'-deamino-4'-ureido (7-9) and 4'-deamino-4'-thioureido (10) derivatives were synthesized by trimethylsilylation of PRMs A and C, followed by condensation with appropriate reagents. 4'-Deamino-4'-guanidino (5) and 4'-deamino-4'-amidino (6) derivatives were synthesized by catalytic hydrogenation of 4 and 2, respectively. 4'-N-Nitroso derivative 3 was prepared by treatment of PRM A with nitrous acid. Among these compounds, the 4'-N-cyano derivative of PRM C (2) exhibited in vitro and in vivo antifungal activities comparable to the parent compounds together with good water-solubility.