Inhibitors of Steroid Biosynthesis: Preparation of 5,10-Secoestr-4-ynes

This paper describes two novel syntheses of 5,10-secoestr-4-yne-3,10,17-trione, a compound which has been shown previously to be a powerful irreversible inhibitor of both bacterial and mammalian Δ⁵-3-keto steroid isomerases. One synthetic route makes available 3β-hydroxy-4-acetylenic 5,10-seco steroids and the other provides 3α-hydroxy-4-acetylenic 5,10-seco steroids. Stereospecific routes to these epimeric α,β-acetylenic alcohols were developed because of their potential utility as mechanism-based inhibitors of the corresponding 3α- and 3β-hydroxy steroid dehydrogenases.