Collect. Czech. Chem. Commun. 2000, 65, 77-82

Synthesis and Biological Activity of New 16,17-Secoestrone Derivatives

Suzana Jovanović-Šantaa,*, Silvana Andrićb, Radmila Kovačevićb and Vjera Pejanovića

a Institute of Chemistry, Faculty of Science, University of Novi Sad, Trg Dositeja Obradovica 3, YU-21000 Novi Sad, Yugoslavia
b Institute of Biology, Faculty of Science, University of Novi Sad, Trg Dositeja Obradovica 2, YU-21000 Novi Sad, Yugoslavia


Starting from estrone 3-benzyloxy-17β-hydroxyestra-1,3,5(10)-trien-16-one oxime (3b) was synthesized, which underwent Beckmann fragmentation giving the 3-benzyloxy-17-oxo- 16,17-secoestra-1,3,5(10)-triene-16-nitrile (4b). Sodium 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 5b in presence of Pd/C as a catalyst, yielding 3-hydroxy-17-oxo-16,17-secoestra- 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 estrogenic activity, whereas compounds 4a, 5a and 5b exhibited moderate antiestrogenic effect.

Keywords: Steroids; Secosteroids; Hormones; Estrogenes; Estrogenic activity; Beckmann fragmentation reaction; Hydrogenolysis.

References: 9 live references.