Synthesis of (3<i>S</i>,5<i>R</i>)-Carbapenam-3-carboxylic Acid and Its Role in Carbapenem Biosynthesis and the Stereoinversion Problem

Abstract

(5R)-Carbapenem-3-carboxylic acid is the simplest structurally among the naturally occurring carbapenem beta-lactam antibiotics. It is the produced from (3S,5S)-carbapenam-3-carboxylic acid utilizing a remarkable stereoinversion/desaturation process by CarC (carbapenem synthase), an alpha-ketoglutarate dependent non-heme iron oxygenase. In this communication, we demonstrate for the first time that the epimeric (3S,5R)-carbapenam-3-carboxylic acid is an intermediate in the overall catalytic cycle to the carbapenem antibiotic. The role of alpha-ketoglutarate in the stereoinversion and desaturation processes is also examined.