Synthesis and progestational activity of 16-methylene-17 alpha-hydroxy-19-norpregn-4-ene-3,20-dione and its...

16-Methylene-17 alpha-hydroxy-19-norpregn-4-ene-3,20-dione 1 and its 17 alpha-acylated derivatives were synthesized. The length of the 17 alpha-side-chain ranges from C2-C6. As anticipated, compound 1 did not show any progestational activity or receptor binding activity; whereas, the acylated compounds, especially the butyrate, showed remarkable ability to bind to progesterone receptors. These compounds also showed progestational activity in an in vitro T47D cell culture assay in which progestins increase alkaline phosphatase activity and in an in vivo ovulation inhibition assay. All of the compounds synthesized were without estrogenic activities. The results showed that acylation of 16-methylene-17 alpha-hydroxy-19-norprogesterone can increase progestational activity. The progestational activities of these compounds varied with the 17 alpha-side chain.