Studies on penem and carbapenem. I, Syntheses and oral absorption of ester-type prodrugs of sodium (5R,6S)-2-(2-fluoroethylthio)-6-[(1R)-1-hydroxyethyl]penem-3-carboxylate

Acyloxyalkyl esters, alkyloxycarbonyloxyalkyl esters and (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl ester (2h) of (5R,6S)-2-(2-fluoroethylthio)-6-[(1R)-1-hydroxyethyl] penem-3-carboxylic acid were synthesized. Enhanced oral absorption was observed in mice reflecting increased lipophilicity, compared with the parent 1 itself. Among them, the ester 2h showed a prolonged plasma level and a large area under the blood concentration-time curve (AUC) in rats. These ester-type prodrugs of penem 1 in phosphate buffer (pH 6.86) were much more stable than those of cephalosporins which easily degraded via isomerization to Δ 2 cephalosporins