Steroidal Heterocycles. VI.¹ Formylation of A/B-cis 3-Ketosteroids.² Preparation of 5β-Steroidal[3,2-c]pyrazoles

Abstract

The forniylatiori of 3-ketosteroids of the il/B-cis series has been shown to yield predominantly 2-hydroxymethylene-3keto-5p-steroids rather than 4-hydroxymethylene derivatives. The structures of the formyl derivatives were proved by their conversion to the corresponding 5P-steroidal[3,2-c]pyrazoles and direct comparison of these with authentic samples prepared by catalytic hydrogenation of A4-steroidal [3,2-c]pyrazoles. Only in the 5p-stigmast-22-en-3-one series was evidence found for the formation of a 4-hydroxymethylene derivative as the mirlor product of formylation.The 2-hydroxymet8hy1enc-3-ketosteroids obtained by the condensation of A/B-transand A4-3-ketosteroids with ethyl formate in the presence of base have been employed extensively in recent years as intermediates in the preparation of a variety of substituted steroid^.^ On the other hand, the preparation and use of hydroxymethylene derivatives of A 'B-cis 3-ketosteroids have been reported in detail only by Tsuda and I n work concerned with the methylation of 3-ketosteroid^,^^ 5p-stigmast-22-en-3-one (I) was formylated with ethyl formate and sodium methoxide in benzene, the derivative was methylated, and the formyl group then cleaved with acid. The resulting product was assigned the 4p-methyl structure I1 on the basis of its non-identity with the 2pmethyl analog 111. The latter compound was prepared, in admixture with the da-isomer, by catalytic hydrogenation of 2a-methylstigmasta-4,22-dien-3one in the presence of base. Since both methyl (1) Paper

Novel Protective Group Synthesis of Androgen Receptor Modulators with Steroidal and Nonsteroidal Scaffolds

“…The crude product was purified by column chromatography on silica gel by using hexane-ethyl acetate (1:1), to afford 1.35 g of 4 as a colorless solid (68%). To a solution of 0.95 g intermediate (2) in 55 ml of the solvent mixture tetrahydrofuran/methanol/water 7:2:1 pyridinium tosylate (1.15 g dissolved in 20 ml tetrahydrofuran/methanol/water 7:2:1) was added at room temperature. Subsequently, this was followed by 8 h stirring at 50°C.…”

Novel Protective Group Synthesis of Androgen Receptor Modulators with Steroidal and Nonsteroidal Scaffolds

“…The formation of two major byproducts can be observed via TLC (Seebach-staining). The mixture was filtered through a short pad of silica and the corresponding ethanol solution was evaporated to yield 1.90 g of a colorless solid [1,2]. The crude product was purified by column chromatography on silica gel by using hexane-ethyl acetate (1:1), to afford 1.35 g of 4 as a colorless solid (68%).…”

“…1.09 g Sodium hydride was added in small portions before the reaction mixture was flushed with argon and stirred at room temperature for 1 h. After this period, the dropwise addition of 7.77 g pure ethyl formate through the septum was administered. The reaction mixture was stirred over night at ambient temperature [1,2].…”

“…This solution was hydrogenated in a pressure vessel (Parr reactor) with 6.00 g palladium on charcoal (5%) at 4 bar and room temperature for 24 h. The mixture was filtered twice through paper and the corresponding ethanol solution was evaporated, to yield 9.50 g colorless oil, still contains traces of charcoal and ethanol. The crude product was purified by column chromatography on silica gel by using hexane-ethyl acetate (8:2) as an eluent, to afford 5.45 g purified material as a colorless solid (69%) [1,2].…”

Synthesis and antiproliferative activity of new D-homo and D-seco androstane derivatives

“…pirazolini su poznati i po svojoj anti-inflamatornoj aktivnosti. [74][75][76][77][78] Stanozolol ( 81,82 Kao što je ranije re eno, važnu klasu derivata testosterona predstavljaju 17metil derivati, sa modifikovanim A-prstenom, koji su se pokazali kao dobri anaboli koandrogeni steroidi, oksandrolon (10) i oksimetolon (12) (slika 2.4., str. 16).…”