Synthesis and biological evaluation of penem inhibitors of bacterial signal peptidase

We report the first synthesis of a 5S penem, known to bind bacterial type I signal peptidase, from the commercially available and inexpensive 6-aminopenicillanic acid. We report the first in vivo activity of the compound and use structure–activity relationship studies to begin to define the determinants of signal peptidase binding and also to begin to optimize the penem as an antibiotic.

Graphical abstractThe synthesis of a 5S penem inhibitor of bacterial signal peptidase is reported and shown to have activity against human pathogens and to be potentially optimizable for spectrum and activity.Figure optionsDownload full-size imageDownload as PowerPoint slide