Synthesis and biological evaluation of penem inhibitors of bacterial signal peptidases

D.A. Harris, M.E. Powers, F.E. Romesberg, Bioorg. Med. Chem. Lett. (2009) 19:3787-3790.
pubpic2009harrisWe 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, and we use structure–activity relationship studies to begin to define the determinants of signal peptidase binding and to optimize the penem as an antibiotic.