Synthetic approaches toward total synthesis of 12β-methyl- and 12-methylene-19-norpregnanes

The effect of a substituent in the 12-position of progestagens was studied. To this end, various approaches toward the preparation of 12β-alkyl- and 12-alkylidenenorpregnanes were investigated. Eventually, the desired compounds 17β-hydroxy-12β-methyl-18α-homo-19-nor-17α-pregn-4-en-20-yn-3-one ( 37) and 17β-hydroxy-12-methylene-18α-homo-19-nor-17α-pregn-4-en-20-yn-3-one ( 38) were obtained in racemic form by total synthesis; they were shown to lack progestagenic activity.