Synthesis of (5S)-Tricyclic Penems as Novel and Potent Inhibitors of Bacterial Signal Peptidases

Abstract

(5S)-Tricyclic penems were synthesized for the first time via intramolecular cyclization of penem epoxy amides catalyzed by a weak Lewis acid [Mg(ClO₄)₂]. Due to the high degree of ring strain in these molecules, mild reaction conditions were developed to successfully construct penem intermediates and the tricyclic penem final products. These tricyclic penems and other newly synthesized (5S)-penem esters and amides exhibited good-to-high potency when tested as inhibitors of bacterial signal peptidases.

tricyclic penems - β-lactams - cyclization - epoxidation - signal peptidase - inhibitors

References

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