Transition metal complexes catalyzed synthesis of biologically active estrone derivatives

This thesis relates to the preparation and use of new non-estrogenic ligands selective for certain types of the 17β-hydroxysteroid dehydrogenase superfamily (17βHSD). Such nonestrogenic compounds, which selectively regulate the activity of 17βHSD are believed to offer new solutions in endocrine therapy, diagnosis and treatment of estrogen-dependent types of diseases. In recent years in the laboratories of my supervisor prof. Kotora differently substituted steroid derivatives with interesting biological properties were prepared. Based on the gained experiences, it was decided to prepare C-15 estrone derivatives. Such compounds are mostly unexplored, and therefore they might be a new class of interesting biologically active compounds. A method was developed for the preparation of C-15 estrone derivatives. Estrone, the starting material for the synthesis, was first converted to the appropriate intermediate, protected estra-1,3,5(10),15-tetraene-17-one. Conjugate addition of vinylmagnesium bromide to this enone yielded the starting material for further reactions, 15β-vinylestrone. Cross metathesis of 15β-vinylestrone with suitable terminal olefins provided large series of C-15 estrone derivatives with perfluoroalkylated, aliphatic and aromatic side chains. Selected unsaturated derivatives were tested..