Synthesis and estrogenic activity screening of some 6,9-disubstituted estradiol derivatives

Oxidation of estradiol dipropionate ( 1) with chromium( VI) oxide-3,5-dimethylpyrazole complex yielded 9 alpha-hydroxy-6-oxoestra-1,3,5( 10)-triene- 3,17 beta-diyl dipropionate ( 2) and 6-oxoestra- 1,3,5( 10)- triene- 3,17 beta-diyl dipropionate ( 3). Dehydration of compound 2 with phosphorus( V) oxide or acetic anhydride gave 6-oxoestra- 1,3,5( 10), 9( 11)- tetraene- 3,17 - diyl dipropionate ( 5). Reduction of compounds 2 and 5 with sodium borohydride afforded 3,6, 9 alpha-trihydroxyestra- 1,3,5( 10)- triene- 17 beta-yl propionate ( 4) and 3,6 beta-dihydroxyestra-1,3,5( 10), 9( 11)- tetraene-17 beta-yl propionate (6), respectively. The action of thionyl chloride on compound 2 yielded 6-hydroxyestra-1,3,5( 10), 6,8-pentaene-3,17 beta-diyl dipropionate (7). Biological tests in vivo of these compounds showed a moderate antiestrogenic activity of compound 4.