The 4' -7V-alkyl (1~10) and 4' -7V-acyl derivatives (ll~21) ofpradimicins (PRMs) were synthesized by trimethylsilylation of PRMsA, C and FA-1 followed by condensation with appropriate alkylating and acylating agents. The 4'-hydroxy derivatives (23 and 24) were synthesized from PRMFA-2 in a 3-step sequence. Among these compounds, the 4'-N-carboxylsubstituted alkyl (1, 5, 8 and 10), 4'-Af-formyl (ll) and 4'-axial-hydroxy (23) derivatives retained the antifungal activity of the parent compoundsand showedgreat improvementin water solubility.The pradimicins (PRMs) are a new family of antibiotics ( Fig. l)1^that exhibited broad-spectrum antifungal activity both in vitro and in vivo. Although they are relatively non-toxic, their limited solubility in aqueous media prompted us to initiate chemical modification of PRMsfocused on the C4'-position6'7) in order to improve water-solubility. The objectives in this program were to determine the limitations of modification, establish structure-activity relationships and identify a compoundfor development. Herein, wedescribe the syntheses and in vitro activities of the PRMderivatives prepared.
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