Novel Estrones by Oxidation of the Benzylic Positions of the Estrane Skeleton with tert-Butyl Hydroperoxide and Cobalt Acetate

Four new estrone derivatives were isolated after treatment of estrone 3-methyl ether (3-methoxyestra-1,3,5(10)-trien-17-one (3) with tert-butyl hydroperoxide and cobalt acetate. Three of the four steroidal compounds - the 9α-(tert-butylperoxy)-6-one 4, the 9α-hydroxy-6-one 5, and the 9β-hydroxy-6-one 7-originated from oxidation at the 6- and 9-positions. In contrast, oxidation of 3 to a 9β-(tert-butylperoxy) compound afforded the 8-hydroxy-9-cyclodecanone derivative 6 through a molecular rearrangement involving the cleavage of the 8-9 bond. The structures of the compounds were secured by spectroscopic evidence including COSY, HSQC, and NOESY experiments combined with X-ray crystallographic analysis and molecular modeling studies.