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Synthesis and Evaluation of Oxodioxolenylmethyl Carbamate Prodrugs of Pseudomycins

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journal contribution
posted on 30.06.2001 by Xicheng Sun, Michael Rodriguez, Doug Zeckner, Bobbie Sachs, William Current, Robert Boyer, Jonathan Paschal, Carl McMillian, Shu-Hui Chen
With the aim of increasing therapeutic indexes of novel cyclic depsinonapeptide pseudomycins, we synthesized and evaluated a series of mono-, di-, and trioxodioxolenylmethyl carbamate prodrugs (2 and 4) of pseudomycin B 1 and pseudomycin C‘ 3. It is rather encouraging to note that several members of the newly synthesized prodrugs described herein (e.g., 2a, 2e, and 4e) exhibited comparable in vivo efficacy to that achieved by the parent compounds, yet free of tail vein irritation and histamine induced toxicity in vivo.