Synthesis of Z ‐ and E ‐1‐Methyl‐2‐(1‐hydroximinoethyl)‐6‐methoxy‐3,4‐dihydronaphthalene and Evaluation as Inhibitors of 17α‐Hydroxylase‐C17,20‐Lyase (P450 17)

The synthesis and biological evaluation of Z ‐ and E ‐1‐methyl‐2‐(1‐hydroximinoethyl)‐6‐methoxy‐3,4‐dihydro‐naphthalene ( Z ‐1 and E ‐1 ) as nonsteroidal inhibitors of 17α‐hydroxylase‐C17,20‐lyase (P450 17, CYP17) is described. Z ‐1 and E ‐1 were separated by column chromatography and identified by 1 H NMR. The synthesis of the key compound 3 was accomplished by a new reaction acetylating the 1‐methyl‐6‐methoxy‐3,4‐dihydronaphthalene compound 2 under Friedel‐Crafts conditions. Compound 2 was obtained from the 1‐tetralone via Wittig reaction. Using a microsomal fraction of human testicular enzyme, Z ‐1 and E ‐1 inhibited the target enzyme only marginally.