Synthesis and pregnancy-inhibiting activity of 7-substituted androst-5-ene derivatives

Synthesis of 7-aryl/allyl-substituted androstene derivatives 3a through 3g has been carried out by Grignard reaction on 3β,17β-diacetoxyandrost-5-en-7-one ( 2) with aryl/allyl magnesium bromide. Iso-meric mixture of products 3b and 3c 3e and 3f 3h was separated by column chromatography. Stereo-chemical assignment at C-7 has been made on the basis of 13C nuclear magnetic resonance studies and chemical considerations. Compounds 6a and 6b were synthesized by alkylation of compound 5 with β-(N,N-diethylamino)ethyl chloride hydrochloride and 1-(2-chloroethyl)pyrrolidine hydrochloride, respectively. Compound 3g(isomeric mixture) prevented pregnancy in 60% of rats at 10 mg/kg daily dose administered orally on days 1 to 7 of pregnancy; however, its only isolable 7β-hydroxy isomer, 3h, was inactive at this dose.