SU434651A3 - METHOD OF OBTAINING 3-CYCLOPENTYLOXY-7a-METHYL-3, 16a, 17cc - TRIOXYSTRAEN - Google Patents

Description

one

The invention relates to the field of the preparation of new hydroxyl-containing steroids of the estradia series, namely, 3-cyclopentyloxy-7a-methyl-3, 16a, 17a - trioxyetratriene or its 16,17-diacetate with high physiological activity.

The proposed method is based on the reaction of hydroxylation of unsaturated steroids using osmium tetroxide, followed by reductive cleavage of the resulting osmiates.

By applying the known hydroxylation reaction to 3-pentyloxy-7a-methyl-A1-estrate tetraenes, new hydroxyl-containing steroids of the estrana series, possessing valuable properties, are obtained.

The proposed method for the preparation of 3-cyclopentyloxy-7a-methyl-3, 16a, 17a-trioxyestratriene of formula (I)

E

treated with osmium tetroxide, the resulting osmium is subjected to reducing

16a, 17a-diol, which is formed in this way, is either isolated or acetylated by known methods into 16, 17-diacetate.

The reductive cleavage of osmiat is carried out, for example, using aqueous

mannitol solution, sodium sulfite or lithium aluminum hydride.

The starting compounds can be obtained by known methods from the corresponding 3-oxysteroids by esterification with cyclopentanol.

or their 16, 17-diacetate is that the compound described by formula (II)

Example 1. 4.5 g of 3-cyclopentyloxy-7methyl-AA5 () -estrateteraene is dissolved in 450 ml of absolute ether and 4.5 ml of pyridine, treated with 4.1 g of osmi tetraoxide in 60 ml of absolute ether at room temperature and kept in the absence of air for three days at a set temperature. The osmium ether was filtered off with suction, washed with ether and boiled with 420 ml of 95% ethyl alcohol and

420 ml of 5% -Horo sodium bisulfite solution for 2 hours under reflux. After cooling to room temperature, osmium was separated using celite, the filtrate was evaporated in a water jet pump vacuum, treated with water and extracted with two portions of chloroform. The organic extracts are washed with water, dried and evaporated under a water jet vacuum. The resulting crude product is dissolved in toluene and chromatographed on a silica gel basis. A pure amorphous 3-cyclopentyloxy-7a-methyl-16a, 17a-dioxy D1, 3, 5 (10). Estratriene, and about + 32 ° is obtained.

Used as the starting material, 3-cyclopentyloxy-7a - methyl - Dedesu). estratetraten is obtained by treating the corresponding free 3-hydroxy compound with cyclopentyl bromide.

Example 2. 5.5 g of 3-cyclopentyloxy-7methyl-16a, 17a - dioxy-D1A5 (10). Estratriene is dissolved in 35 ml of pyridine, treated with 35 ml of acetic anhydride and incubated for 18 hours at room temperature. The reaction mixture was poured into ice water, stirred for 1 hour and treated with ether. The resulting crude product is chromatographed on silica gel to give pure amorphous 3-cyclopentyl.xy-7a-methyl-16a, 17-diacetoxy-D1. (10) -estratriene, absorption spectrum in the ultraviolet region, mmk:

223 (6 9000), 279 (8 2000) and 288 (), aJD + 14 ° (chloroform).

Subject invention

The method of obtaining 3-cyclopentyloxy-7a-methyl-3, 16a, 17a-trioxyestratriene formula

or its 16,17-diacetate, characterized in that the compound described by the formula

SN P

is treated with osmium tetroxide, the resulting osmium is subjected to reductive cleavage and the resulting 16a, 17a-dioxo compound is either isolated or converted into 16,17-diacetate by known methods.