Alkylated steroids. Part 3. The 21-alkylation of 20-oxopregnanes and synthesis of a novel anti-inflammatory 16α,17α,21-trimethyl steroid (Org 6216)

Abstract

The development of a 21-alkylation reaction which proceeds via the lithium 20(21)-enolate is described and its scope demonstrated by the preparation of a variety of 21-alkylpregnane derivatives. Application of this process to 11β-acetoxy-16α,17α-dimethyl-5α-pregnane-3,20-dione (28a) and its 5β-analogue (28b) led to the corresponding 16α,17α,21-trimethyl derivatives. Several routes from these saturated trimethylpregnane-3,20-diones to 11β-hydroxy-16α,17α,21-trimethylpregna-1,4-diene-3,20-dione (Org 6216) were explored. The best method gave Org 6216 in 75% yield.