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

Abstract

(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. Thein vitrobinding of the 3α-fluorides and the corresponding 3α-alcohols to the GABAAreceptor was established using [3H]muscimol and [35S]-tert-butylbicyclo[2.2.2]phosphorothionate as ligands.