N-Acyloxymethyl carbamate linked prodrugs of pseudomycins are novel antifungal agents

We describe herein the synthesis, bioconversion, antifungal activity, and preliminary toxicology evaluation of a series of N-acyloxymethyl carbamate linked triprodrugs of pseudomycins. The syntheses of these prodrugs (3–6) were achieved via simple N-acylation of PSB (1) or PSC′ (2) with various [12] (7–9). As expected, upon incubation with mouse and/or human plasma, many of these prodrugs (3, 5, and 6) were converted to the parent compound within a few hours. Of particular significance, two pseudomycin triprodrugs (5 and 6) showed excellent in vivo efficacy against systemic Candidiasis without tail vein irritation being observed.