ANTIFUNGAL ACTIVITIES OF PRADIMICIN DERIVATIVES MODIFIED AT C4'-AMINOGROUP

In order to explore potent derivatives of pradimicins (PRMs), modifica tion of their C4'-amino group was carried out. 4'-N-Cyano (1, 2), 4'-d eamino-4'-nitroguanidino (4), 4'-deamino4'-ureido (7-9) and 4'-deamino -4'-thioureido (10) derivatives were synthesized by trimethylsilylatio n 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 nit rous 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.