ANDROGEN RECEPTOR AFFINITY OF 5'-ACYL FURANOSTEROIDS

Syntheses of 5'-acyl furanosteroids are described from the correspondi ng unsubstituted [3,2-b]furanosteroids using acid anhydrides and acid chlorides in the presence or absence of Lewis acids. New methods have been developed to prepare 5'-acetyl derivatives: reduction of a 5'-tri chloroacetyl intermediate either by sodium formaldehyde sulfoxylate or with 10% Pd/C. Most of these 5'-acyl derivatives bind to the rat vent ral prostate androgen receptor. However the antiandrogenic activity wa s diminished when compared with 4, 5'-methylsulfonyl furanosteroid. Bi ological studies revealed that 5'-acyl furanosteroids were either andr ogens or modest antiandrogens. The electrostatic potential maps of the substructures of 3, 4, and 5'-acetyl syn- and anti-furanosteroids sho wed striking differences which may explain, to some extent, the lack o f significant antiandrogenic activity of 5'-acyl furanosteroids.