Design, Synthesis, and Antimicrobial Evaluation of a Novel 3’-c-acetohydrazide Puromycin Analog

This presentation was given at the 71st Southwest/67th Southeast Regional Meeting of the American Chemical Society

Synthesis, Stereochemical Characterization, and Antimicrobial Evaluation of a Potential Non-Nephrotoxic 3\u27-c-acethydrazide Puromycin Analog

Puromycin is a peptidyl nucleoside endowed with significant antibiotic and anticancer properties, but also with an unfortunate nephrotoxic character that has hampered its use as a chemotherapeutic agent. Since hydrolysis of puromycin\u27s amide to puromycin aminonucleoside is the first metabolic step leading to nephrotoxicity, we designed a 3′-C-hydrazide analog where the nitrogen and carbon functionality around the amide carbonyl of puromycin are inverted. The title compound, synthesized in 11 steps from D-xylose, cannot be metabolized to the nephrotoxic aminonucleoside. Evaluation of the title compound on Staphylococcus epidermidis and multi-drug resistance Staphylococcus aureus did not show significant antimicrobial activity up to a 400 μM concentration