SYNTHESIS AND BIOLOGICAL TESTING OF A,18-CYCLO-12A,12B-DIHOMO-13-ALPHA-ESTR-4-EN-3-ONE - AN INTERESTING RU-38-486 ANALOG

A partial synthesis of the title compound, 4'-(dimethylamino)-17 beta- hydroxy-17 alpha-(1-propynyl)benzo[12,12a]11 alpha,18-cyclo-12a,12b-di homo-13 alpha-estr-4-en-3-one 1, is reported The key step in this synt hesis represents an intramolecular alkenylaryl radical cyclization. Tr eatment of enyl]gona-5,9(11)-diene-3,17-dione-3,17-bis[cyclic acetal] 5 with tributyl tin hydride and a radical initiator introduces the des ired 11 beta,18-bridge. The reduced progesterone receptor affinity of this RU 38 486 analog contributes valuable information to the empirica l characterization of the steroid binding site of the receptor protein and explains the observed lack of in vivo antigestational activity.