809. Modified steroid hormones. Part IV. 6-Methylpregnane derivatives

Abstract

3P-Hydroxy-25D-spirost-5-ene (11) has been transformed into its 6methyl derivative (cf. VI) by two methods. Its degradation gave 3P-acetosy-6-methylpregna-5 : 16-dien-20-one (VIII; R = Ac), which was transformed into 6-metliylpregnenolone (VII; R = H).Oppenauer oxidation of the last compound gave Ga-methyl-17a-pregn-4ene-3 : 20-dione and a smaller quantity of 6a-methylprogesterone (X; R = ---Me, -H). The last compound was independently obtained from pregnenolone.The 16-dehydro-derivative (IV) of 6a-methylprogesterone has been prepared.

Neurosteroid Analogues. 10. The Effect of Methyl Group Substitution at the C-6 and C-7 Positions on the GABA Modulatory and Anesthetic Actions of (3α,5α)- and (3α,5β)-3-Hydroxypregnan-20-one

“…(5r,6β)-6-Methylpregnane-3,20-dione (4a) and (5β,6β)-6-Methylpregnane-3,20-dione (4b). The steroid (6β)-6-methypregn-4-ene-3,20-dione (3, 563 mg, 1.72 mmol) prepared according to the literature methods 20 was dissolved in EtOH (120 mL) containing 5% Pd/CaCO3 (150 mg) and KOH (240 mg, 4.29 mmol) dissolved in water (1 mL). The mixture was hydrogenated at room temperature under H 2 (50 psi) for 6 h. The reaction mixture was filtered and the filtrate diluted with water and extracted with Et 2O.…”

“…The starting material, (6β)-6-methylpregn-4-ene-3,20-dione (3), was prepared from commercially available pregnenolone acetate according to literature procedures. 20 Catalytic hydrogenation of steroid 3 using 5% Pd/CaCO 3 under basic conditions gave a 90% yield of a 3.4:1 mixture of the C-5 epimers 4a (5R-configuration) and 4b (5β-configuration). Under the same experimental conditions, hydrogenation of progesterone gives a product in which the epimer having the 5β-configuration is the major product.…”

STEROIDS AND RELATED PRODUCTS: XXI. THE SYNTHESIS OF 17α-Bromo-6α -METHYLPROGESTERONE

“…Deketalization with acetone and p-toluenesulphonic acid (22) afforded 3P,5cu-dihydroxy-BP-methylpregnan-20-one (LX), which was converted directly to the acetate IXa. The structure of the intermediates V, I X , and IXa was confirmed by oxidation, with chromic acid and sulphuric acid in acetone (26,27), of the dihydroxy ketone I X to the known (28,29) 5a-hydroxy-6P-methylpregnane-3,20-dione (XIII). Since this diketone XI11 is readily converted to 6a-methylprogesterone (XIV) (and also to its 60-epimer) (28, 29, cf.…”

“…A"l"-6a-;lJethylpregnadiene-S,20-dione (6a-,4fethy1-16-dehydroprogesterone) ( X V ) (29) X solution of 60 mg of 17a-broino-6a-methylprogesterone (XII), m. …”

“…3 and 19). The structure and the stereochemistry of the slieleton were proved by reduction of the progesterone derivative X I I , with zinc and acetic acid, to 6a-methylprogesterone (XIV) (28,29)' and was further confirmed by dehydrobromination with dimethylformamide and lithium chloride (cf. ref.…”