Iodine-promoted cleavage of the C-17-dihydroxyacetone side chain of corticosteroids in aqueous ammonia water

Abstract

A convenient approach to 17-ketosteroids by the iodine-promoted cleavage of the C-17-dihydroxy acetone side chain of corticosteroids is described. Treatment of steroids containing the C-17-dihydroxyacetone side chain with iodine and an excess of aqueous ammonia in acetonitrile at 50°C, affords high yields of the corresponding 17-ketosteroids.

Bismuth(III) Reagents in Steroid and Terpene Chemistry

“…A quite recent report showed that Bi(OTf) 3 ·xH 2 O is an efficient catalyst for the conversion of corticosteroids into highly functionalized 17-ketosteroids, by cleavage of the C17-dihydroxyacetone side chain [ 99 ]. This reaction was typically performed using large amounts of oxidative or basic reactants [ 100 , 101 , 102 ]. The use of other bismuth(III) salts and other solvents has been tested, however the best results have been obtained with 0.05 eq.…”

Electrochemically Enabled One‐Pot Multistep Synthesis of C19 Androgen Steroids

“… [7] Removal of the C17 side chain of corticosteroids has traditionally involved the use of excess amounts of strong oxidizing agents such as NaBiO 3 , [8] NaBH 4 /NaIO 4 , [9] CrO 3 [10] or MnO 2 [11] . Additional methods involving excess I 2 /NH 3 [12] and strong bases [13] have also been developed, although with either moderate yields or limited applicability. More recently, cleavage of hydroxyacetone side chains with bismuth(III) catalysts has been reported [14] .…”

“…[7] Removal of the C17 side chain of corticosteroids has traditionallyi nvolved the use of excess amounts of strong oxidizing agents such as NaBiO 3 , [8] NaBH 4 /NaIO 4 , [9] CrO 3 [10] or MnO 2 . [11] Additional methods involving excessI 2 /NH 3 [12] and strong bases [13] have also been developed,a lthough with either moderatey ields or limited applicability.M ore recently,c leavageo fh ydroxyacetone side chains with bismuth(III) catalysts has been reported. [14] Due to the shortcomings of these methods and the difficulties associated with the selective side chain removal without degradation of the androstane skeleton, microbial approaches from phytoster-ols have been intensely investigated.…”

Bismuth(III) Triflate-Catalyzed Direct Conversion of Corticosteroids into Highly Functionalized 17-Ketosteroids by Cleavage of the C17-Dihydroxyacetone Side Chain

“…Later, an optimized procedure that uses 5.0 equiv of sodium methoxide in refluxing 1,4-dioxane has been described . More recently, the direct conversion of corticosteroids into 17-ketosteroids by using iodine in the presence of an excess of aqueous ammonia has also been reported …”