Collect. Czech. Chem. Commun.
2005, 70, 63-71
https://doi.org/10.1135/cccc20050063
Synthesis, X-ray Crystal Structure and Antiestrogenic Activity of 17-Methyl-16,17-secoestra-1,3,5(10)-triene Derivatives
Marija N. Sakača,*, Dušan A. Miljkovića, Katarina M. Penov Gašia, Mirjana Popsavina, Olivera R. Klisurićb, Slobodanka M. Stankovićb, Silvana Andrićc and Radmila Kovačevićc
a Department of Chemistry, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Trg Dositeja Obradovića 3, Serbia and Montenegro
b Department of Physics, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Trg Dositeja Obradovića 4, Serbia and Montenegro
c Department of Biology, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Trg Dositeja Obradovića 2, Serbia and Montenegro
Abstract
Starting from 3-(benzyloxy)-16-(hydroxyimino)-estra-1,3,5(10)-trien-17-one (1) several 17-methyl-16,17-secoestratriene derivatives were synthesized. In the first step of synthesis, hydroxyimino ketone 1 was transformed into 3-(benzyloxy)-16-(hydroxyimino)-17α-methylestra-1,3,5(10)-trien-17β-ol (2), the Beckmann fragmentation of which gave 3-(benzyloxy)-17-methyl-17-oxo-16,17-secoestra-1,3,5(10)-triene-16-nitrile (3a). Reduction of 3a with sodium borohydride yielded (17S)-3-(benzyloxy)-17-hydroxy-17-methyl-16,17-secoestra-1,3,5(10)-triene-16-nitrile (4a), whose configuration at the newly formed chiral center was established by X-ray structural analysis. Catalytic hydrogenation of compound 3a under different reaction conditions yielded 3-hydroxy-17-methyl-17-oxo-16,17-secoestra-1,3,5(10)-triene-16-nitrile (3b) and 16-amino-17-methyl-16,17-secoestra-1,3,5(10)-triene-3,17-diol (6b). Biological tests in vivo of compounds 3b and 6b showed their moderate antiestrogenic activity.
Keywords: 17-Substituted 16,17-secosteroids; Steroids; Antiestrogenic activity; Aromatase inhibition; X-Ray analysis; Oximes; Nitriles.
References: 9 live references.
