The First Syntheses of 16β-Chloro- and 16β-Bromo-Cyproterone Acetate

In 2003, Sakee, Kongkathip, and Kongkathip successfully synthesized 16β-chloro- and 16β-bromo-cyproterone acetate for the first time. These compounds were of interest for their potential anti-androgenic and progestational activities, which could be beneficial in treating diseases related to androgens. The synthesis of 16β-chlorocyproterone acetate was completed in eight steps with a final yield of 6.5% starting from 16-dehydropregnenolone acetate, with a crucial step being base-induced epoxide formation. The 16β-bromocyproterone acetate was subsequently prepared from the chloro derivative. Although the paper provided detailed experimental procedures and yields for each step, as well as characterization data for intermediates and final products, the biological activities of these compounds were to be published at a later date.