Collect. Czech. Chem. Commun. 2002, 67, 30-46

3α-Fluoro Analogues of "Allopregnanolone" and Their Binding to GABAA Receptors

Barbora Slavíková*, Alexander Kasal, Hana Chodounská and Zdena Krištofíková

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic


(Diethylamino)sulfur trifluoride (DAST) was used for the preparation of 3α-fluorides (e.g., 3α-fluoro-5α-pregnane-12,20-dione, 3α-fluoro-16α-[(methoxycarbonyl)methyl]-5α-pregnan-20-one, methyl 3α-fluoro-5α-androstane-17β-carboxylate, 3α-fluoro-5β-pregnan-20-one) from the corresponding 3β-alcohols and for the preparation of 3,3-difluorides from 3-ketones (e.g., 3,3-difluoro-5α-pregnan-20-one). Boron trifluoride etherate was used for the conversion of an epoxide into 3α-fluoro-2β-hydroxy-5α-pregnan-20-one. The in vitro binding of the 3α-fluorides and the corresponding 3α-alcohols to the GABAA receptor was established using [3H]muscimol and [35S]-tert-butylbicyclo[2.2.2]phosphorothionate as ligands.

Keywords: Allopregnanolone; Epalon; Neuroactive steroids; Fluorosteroids; Fluorination; 1H NMR spectroscopy.

References: 24 live references.