An efficient procedure was proposed for the synthesis of 3β-acetoxy-17α-hydroperoxy-16α-methylpregn-5-en-20-one. Optimal conditions were found for the combined process including 1,4-addition of methylmagnesium bromide at the Δ 16 -20-oxo fragment of dehydropregnenolone acetate and autooxidation of resulting bromomagnesium 3β-acetoxy-16α-methylpregna-5,17(20)-dien-20-olate. The subsequent reduction of the 17α-hydroperoxy group and hydrolysis of the 3β-acetoxy group afforded 17α-hydroxy-16α-methyl-substituted dehydropregnenolone acetate and its 3-hydroxy analog in high yield.Corticosteroids occupy an important place among synthetic medicines. 16α-Methylcorticoids, e.g., Dexamethasone, Mometasone, Flumetasone, and their derivatives, have found wide application due to their strong anti-inflammatory and antiallergic activity. Such corticosteroids can be synthesized from pregnanes having a Δ 16 -20-oxo fragment which is necessary for the introduction of 17α-hydroxy and 16α-methyl groups. An example is dehydropregnenolone acetate I; it is an important and most preferred intermediate in the synthesis of steroid drugs of the pregnane series. The presence of a Δ 16 -20-oxo fragment in molecule I makes it possible to use it for the preparation of 17α-hydroxy-16α-methylpregnanes without additional modification. Compound I is obtained by cleavage of diosgenin, i.e., Δ 5 -steroidal sapogenin [1]. Diosgenin is isolated on a large scale from renewable vegetable raw material, rhizomes of wild and cultivated plants belonging to the Dioscoreaceae R. Brown family, which occur mainly in tropical and subtropical regions, in particular in the Far East (Russia) and South-East Asia. Promising Dioscoreaceae species are D. membranacea and D. colletti; they contain 2.3 and 4.4% of diosgenin, respectively [2].17α-Hydroxy and 16α-methyl groups are generally introduced in two steps, the first of these being 16α-alkylation. Attachment of a methyl group at the 16α-position of the Δ 16 -20-oxo fragment in compound I is usually performed by 1,4-addition of methylmagnesium halide in the presence of copper(I) chloride [3]. The subsequent 17α-hydroxylation can be performed via direct oxidation according to [4] and by the Gallagher-Krichevsky method [5]. Both these procedures are based on the oxidation of Δ 17(20) -20-hydroxy derivative, which is formed as a result of preliminary enolization of the C 20 =O group. In the first version, enolization occurs in alkaline medium. The resulting Δ 17(20) -20-hydroxy derivative is subjected to oxidation with molecular oxygen to obtain 17α-hydroperoxide which is then reduced to 17-hydroxy derivative [6]. In the second version, enolization is promoted by an organic acid (as a rule, p-toluenesulfonic acid) in acetic anhydride with simultaneous acetylation of Δ 17(20) -20-hydroxy intermediate generated in situ. The subsequent oxidation of the ∆ 17(20) double bond with a peroxy acid and mild alkaline hydrolysis of 17α,20-epoxide thus formed gave 17α-hydroxy-20-oxo compound.However, acetylation of enolized 20-oxo gro...