SYNTHESIS AND ESTROGENIC ACTIVITY SCREENING OF SOME 6,9-DISUBSTITUTED ESTRADIOL DERIVATIVES

Received January 11, 2005Accepted April 3, 2005Oxidation of estradiol dipropionate (1) with chromium(VI) oxide-3,5-dimethylpyrazole com-plex yielded 9α-hydroxy-6-oxoestra-1,3,5(10)-triene-3,17β-diyl dipropionate (2)and6-oxoestra-1,3,5(10)-triene-3,17β-diyl dipropionate (3). Dehydration of compound 2 withphosphorus(V) oxide or acetic anhydride gave 6-oxoestra-1,3,5(10),9(11)-tetraene-3,17β-diyldipropionate (5). Reduction of compounds 2 and 5 with sodium borohydride afforded3,6β,9α-trihydroxyestra-1,3,5(10)-triene-17β-yl propionate (4) and 3,6β-dihydroxyestra-1,3,5(10),9(11)-tetraene-17β-yl propionate (6), respectively. The action of thionyl chlorideon compound 2 yielded 6-hydroxyestra-1,3,5(10),6,8-pentaene-3,17β-diyl dipropionate (7).Biological tests in vivo of these compounds showed a moderate antiestrogenic activity ofcompound 4.Keywords: Steroids; Estradiol derivatives; Equilenine derivatives; Estrogenic activity;Antiestrogenic activity; Oxidations.