Syntheses of enantiomerically pure (R)- and (S)-bicalutamide

The racemic antiandrogen bicalutamide is the leading antiandrogen used for the treatment of prostate cancer. The (R)-isomer possesses virtually all of the activity, but both isomers are metabolized by the liver. A convenient synthetic route to the active enantiomer would be an attractive option for patients who are hepatically impaired. We now demonstrate a rather short synthesis of (R)-bicalutamide, starting with a naturally occurring, chiral precursor.