Synthesis and biological activity of new 16,17-secoestrone derivatives

Starting from estrone 3-benzyloxy-17 beta-hydroxyestra-1,3,5(10)-trien-16-o ne oxime (3b) was synthesized, which underwent Beckmann fragmentation givin g the 3-benzyloxy-17-oxo-16,17-secoestra-1,3,5(10)-triene-16-nitr (4b). Sod ium borohydride reduction of this compound afforded 3-benzyloxy-17-hydroxy- 16,17-secoestra-1,3,5(10)-triene-16-nitrile (5b). The deprotection of the 3 -hydroxy group was achieved by action of hydrogen upon derivatives 4b and 5 b in presence of Pd/C as a catalyst, yielding 3-hydroxy-17-oxo-16,17-secoes tra-1,3,5(10)-triene-16-nitrile (4a) and 3, 17-dihydroxy-16,17-secoestra-1, 3,5(10)-triene-16-nitrile (5a). In biological tests on experimental animals , compounds 4a, 4b, 5a and 5b showed virtually a complete loss of estrogeni c activity, whereas compounds 4a, 5a and 5b exhibited moderate antiestrogen ic effect.