SU654174A3 - Method of obtaining d-homosteroids - Google Patents

Description

one

A method of populating those not described in the literature) -homoteroids of the general formula is suggested.

ABOUT

i 2 where R and R mean hydrogen or go together

i, 2 ° C-methylene or a C-Cj bond

 hydrogen, fluorine, chlorine, and methyl;

R -OKCH-, acetoxy group or methyl, possessing pharmacological activity.

A known method for the preparation of double bond ketosteroids at positions 1,2 and 6,7, consists in that the corresponding ketosteroid is dehydrated with chlorofuiline p.

The use of a known reaction makes it possible to obtain (not described in the literature) homo-steroids of the indicated

formulas exhibiting horgonal activity.

The purpose of the invention is the expansion of the range of T} - homosteroids with biological activity.

The proposed method of populating B -homosteroids of the above general formula is that B is a homoteroid of the general formula

ten

ABOUT

where R, R, R, have the indicated values,

are dehydrated at positions 1,2 and 6,7, if R and R are hydrogen, or ilIr if loC, 24.-metipene or C-C bond, is dehydrogenated in position 6.7, or if in position 6.7 is present double

the bond is cegiprated at position 1,2, and the dehydrogenation is carried out with hporanip in a solvent, such as t-butanop, or 2,3-dihydro 5, 6 dicyanobenzoquinone in a solvent such as dioxane, preferably at a temperature from lOCf C to the boiling point of the reaction mixture.

The process can be carried out in the presence of L-toluene free acid or without it.

Example. 4.5 g of 17a o -methyl-B-homo - 4,16-pregnadien-3,2 O-dione in U O MP tert-butanod with 5.4 g of hporanil is boiled under stirring for 18 h. Then the reaction mixture is evaporated in vacuo, the residue is dissolved in ether, filtered from unreacted hporanil, and the filtrate is washed with sodium bicarbonate solution and water. The residue obtained after evaporation is chromatographed on silica gel and, after recrystallization from diisopropyl ether / acetone, 2.25 g of 17α о metip-B-homo-4,6,16-pregnatriene-3,2O-dione, m.p. 180181, 5 ° C. UV spectrum: 2284 2690 O.

EXAMPLE 2: 10 g of 17 ° C-methyl-D-Goms) -4.16-pregnadien-3,20-dione in 20 O ml of dioxane are mixed with 20 g of 2,3-dichlorop-5, 6-dicyanobenzoksinon and 1 After the reaction mixture is evaporated in vacuo, the residue is dissolved in ether, filtered off from insoluble hydroquinone, and the filtrate is washed with a solution of sodium bicarbonate and water. The residue obtained after evaporation is chromatographed on silica gel. After recrystallization from diisopropyl ether / acetone, 5.6 g of 17a are obtained (X-metip-B-homo-1, 4,6,16-pregnatetra-3,2O-dione,

mp.172-174.5V UV spectrum: 1170О, 625.9880, е, „11100.

PRI me R 3. 7.6 g of 17 ° C-hydroxy D-homo-4, B, 16-pregnatriene-3,2O-dirna is stirred in 190 ml of absolute dioxane with 7.6 g of 2,3-dihpor-5. , 6-dicyanobenzoquinone for 18 h at 1OO C. Then it is filtered off from the hydroquinone released, washed well with ether, the filtrate is washed with sodium bicarbonate solution and water. After evaporation, the residue is chromatographed on silica gel, and after recrystallization from diisopropyl ether / acetone, 4.4 g of 17ac-hydroxy-T} -homo-1,4,6, 1b-pregnatetra-3,20-diene are obtained, m.p. 196198 S.

UV spectrum: e „, 12500,. 9420,

221

€ 12,800.

Example 4. 1g 17a-acetoxy-6-chloro-TZ -homo-pregna-4,6,16-triene-3,2O-dione and 1 g of dichlorodicyanobenzoquinone are refluxed in 6O ml of dioxane under argon atmosphere. After 48 hours, 50 O mg of dichlorodicyanobenzoquinone was added, and after 10 hours, another 50 Omg was added. After 7 O hours, the reaction mixture was neutralized with a 20-fold amount of Alox 11 and washed with methylene chloride / acetone. Recrystallization from acetone / hexane gives 500 mg of 17a-acetoxy-6-chloro-T) -homo-pregna-1,4,6,16-tetraen-3, 2O-dione, mp. 198-200 С, s.-24О ° (in donoxane), UV spectrum:

C229 258 - ° ® ° 298 Example. Under the conditions of Example 4

get 17AO-hydroxy-0-homopregna-4,6 16-triene-3,2O-dione with so pl. 188-189 0;

17a cC-acetoxy-D-homopregna-4, 6.16-triene-3,2O-dione with m.p. 216218 ° C; .

17a oC-acetoxy-6-methyl-T) -homopreg at 4,6,16-triene-3,2 O-dionest. Mp. 222223 ° С, ,, 2i800, dCI 184 ° (с - О, 1О in dioxane);

6-chloro-17a D, -methyl-D-homo-4,6, 16, -pregnatriene-3,20-dione with so pl. 178179, 5 ° C, 2 22100,

17 ° C-methyl-1O1 2O (.-Megyl-1) -. -Homo-4,6,16-pregnatriene-3,2O-dione with m. pl. 160.5-167 ° C, 194.00,

6-chloro-17ac1.-Methyl-1oC, 2oC-methylen-D -homo-4,6,16-pregnatriene-3,2O-dione with m. Pl. 183-185 ,, liOO

6-chloro-17ac5C-acetoxy-1cC, 2ciC-Methylene-D-homo-4,6,16-pregnatriene-3,20 dione with so pl. 218-219 ° C, de 174OO,

17a-acetoxy-6-fluoro-T) -homo-4,6,16-pregnatriene-3, 2O with so pl. 205-207 С

-2fi5.24350,

(acetone / hexane) ,, / “i- j J

(with i 0.1% in diokean /,

Claims (1)

17 ° C-acetoxy-6-chloro-B -Homo-4, 6,16-pregnatriene-3,20-dione with m.p. 225-226 ° C ,, - 183 °. (With а 0.1% In dioxane). Invention Formula The method of obtaining B-homosteroids of the general formula. - , 1 where R and R denote hydrogen or ip IcA., 2c-metipene or a C – C bond; R is hydrogen, fluorine, xpori Meti, R-OXY-, acetoxy group or m characterized in that D is homosteroids of the general formula rB j. nfLf where If, R, R, R have the specified 74. they are degusred at positions 1,2 and 6, 7, neither, if R and R are hydrogen, or, if R and R are -1c ", 2C-methylene or a C-C bond, are dehydrated at position 6,7, or if a double bond is present at position 6.7, is dehydrogenated at position 1,2, and the dehydrogenation is carried out using an agent such as chloranyl or 2,3-dichloro-5,6-dicyanobenzoquinone, followed by isolation of the target product. Sources of information taken into account in the examination of l.Ster-oJol peoictions. eel, C. DLeK oissi. lt Zap-G apsazCo, 1Q65, p.ZSO.