The Synthesis of C-21 Substituted Corticosteroids

Abstract

By the reaction of prednisolone and dexamethasone with 2, 2-dimethoxypropane, the synthesis of the 17α, 21-acetonides of these corticosteroids was examined. The utility of the 17α, 21-acetonide function as a protecting group for the labile cortical dihydroxyacetone function is demonstrated. It is particularly valuable for the direct introduction into intact corticoids of C-21 substituents. The synthesis of 21α-methyl and 21-trifluoroacetyl analogs of prednisolone and dexamethasone are described. Condensation of the 17α, 21-acetonides with formaldehyde yields the 21-methylene derivatives 13 and 14, which serve as intermediates for the synthesis of the 21β-nitroethyl derivative 17 and the γ-lactone 19.