Transformations of 3-Hydroxy Steroids with Lewis and Anhydrous Protic Acids: The Case of Pregn-4-en-3beta,17alpha,20beta-Triol

The acid-catalyzed dehydration is one of the mostimportant processes, which transforms 3-hydroxysteroids into their corresponding unsaturatedderivatives. This reaction is of great importancebecause it can produce molecules that play a keyrole in the understanding of the natural metabolismof steroids. Sterol dehydration is generallyperformed with aqueous acidic systems, and thetreatment often affords low yields of the desiredcompounds and ⁄ or complex mixtures of by-products.In this paper, we report the results obtainedfrom the study of the structural and stereochemicaleffects of the acid-induced reaction of pregn-4-en-3beta,17alpha,20beta-triol in anhydrous systems. In particular,the treatment of this trihydroxy steroidmodel with Lewis acids leads to the correspondingD3,5-steradiene as the only product and in veryhigh yields. With Lewis acids, no modifications ofthe 1,2-diol function on the D-ring are observed,even when the reactions are performed at hightemperatures. Protic acid catalysis in non-aqueousorganic solvents causes the formation of an epimericmixture of the corresponding D3,5-steradienederivatives by a partial stereochemical inversionof the asymmetric C-17. The reactivity of the17a,20b-diolic residue is also evaluated by exposingpregn-4-en-3b,17a,20b-triol and the correspondingD3,5-steradiene to the prolonged action ofanhydrous protic acid systems under thermalconditions.