Synthesis and biological activity of some 8α-analogs of steroidal estrogens

8α-Analogs of steroidal estrogens containing a methyl group on C¹ or an oxo group on C⁶ were synthesized with a view to obtain compounds exhibiting selective biological activity, and their steric structure was studied. As shown with 1,3-O-dimethyl-8α-estrone as an example, such compounds in solution can exist as two conformers, whereas the oxo group on C⁶ almost does not affect conformation of the modified derivative as compared to the parent structure. Some newly synthesized compounds exhibited hypocholesterolemic activity in combination with reduced uterotropic effect, which is important for the design of drugs for the treatment of atherosclerosis. 6-Oxo-8α-analogs showed osteoprotective activity, so that introduction of an oxo group into the 6-position is promising from the viewpoint of hormone replacement therapy.