New routes to 4-substituted steroids: synthesis of 4-cyanoprogesterone, a potent inhibitor of the enzyme 5α-reductase

Abstract

Two new synthetic routes to 4-substituted derivatives of progesterone are described: one involves the palladium-catalysed addition of alkenes to 4-(trifluoromethanesulfonyloxy)progesterone, and the other involves the addition of the anion of acetonitrile to the enol acetate, enol lactone 20-acetoxy-4-oxa-3,5-secopregna-5,17-dien-3-one. This second method provides gram quantities of 4-cyanoprogesterone, which proved to be a potent inhibitor of the enzyme 5α-reductase, and thus of considerable interest as a potential agent for the treatment of benign prostatic hyperplasia and prostatic cancer.