Synthesis and evaluation of 17α-(carboranylalkyl)estradiols as ligands for estrogen receptors α and β

• Cross-metathesis reaction between 17α-vinyl- and 17α-allylestradiols with allylcarboranes was studied.
• Two types of 17α-substituted estradiols bearing various carborane cages were synthesized.
• The compounds were tested in cell-based reporter assays.
• The compounds mainly activated estrogen receptors α and β and tended to be weakly selective for ERα.

A series of 17α-(carboranylalkyl)estradiols was synthesized using cross-metathesis reaction of 17α-allyl- and 17α-vinylestradiols with allylcarboranes catalyzed by Hoveyda-Grubbs 2nd generation catalyst. The prepared estradiol derivatives were tested in the panel of cell-based reporter assays including all steroid receptors. The compounds mainly activated estrogen receptors α and β and tended to be weakly selective for ERα. Besides ERα and ERβ, we have also detected a weak agonistic activity on AR and PR at micromolar concentrations. We didn't observe any antagonistic effect with the exception of two receptors: GR and MR which were inhibited with some of the tested ligands. However, the inhibition was detectable at concentrations exceeding by far those needed to activate estrogen receptors.

Cross metathesis offers a convenient approach for synthesis of a series of 17α-(carboranylalkyl)estradiols that tested as ligands for estrogen receptors.Figure optionsDownload as PowerPoint slide