4-methylene-2-octyl-5-oxo-3-oxolanecarboxylic-acid and thiolactomycin

The title congeners were synthesized by employing our efficient synthetic route previously explored for preparing enantiomeric pairs of thiolactomycin and its 3-demethyl derivative. While all the synthesized congeners lacked in vitro antibacterial activity, some of the congeners bearing an (E)-cyclohept-2-enylidenemethyl or an (E)-cyclooct-2-enylidenemethyl group were found to exhibit more potent type I FAS inhibitory activity than (S)-3-demethylthiolactomycin having an unnatural configuration.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Cell Line; Chemistry, Pharmaceutical; Drug Design; Fatty Acid Synthases; Humans; Inhibitory Concentration 50; Microbial Sensitivity Tests; Models, Chemical; Molecular Conformation; Structure-Activity Relationship; Thiophenes