Bioorganic & Medicinal Chemistry Letters 2009-07-15

Synthesis and biological evaluation of penem inhibitors of bacterial signal peptidase.

David A Harris, Michael E Powers, Floyd E Romesberg

Index: Bioorg. Med. Chem. Lett. 19(14) , 3787-90, (2009)

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Abstract

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.