Molecular simplification in bioactive molecules: Formal synthesis of (+)-muconin

The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, is applied to (+)-muconin, an acetogenin with remarkable cytotoxicity. A novel method that enables the stereoselective synthesis of such a natural compound or its enantiomer from a common precursor, affording complete stereochemical control and decrease in the number of chemical steps required, is described.