| Molecular Formula | C20H30O2 |
| Molar Mass | 302.45 |
| Density | 1.0434 (rough estimate) |
| Melting Point | 152-153℃ |
| Boling Point | 383.47°C (rough estimate) |
| Refractive Index | 1.4980 (estimate) |
| Physical and Chemical Properties | Chemical properties crystallize from ether, melting point 152-153 ℃. [α]D 41 (C = 1.0, ethanol). UV maximum absorption (ethanol):240nm(ε15800). Stable to heat, moisture and light. It is converted to 16 α-and 17 α-isomers under the action of sunlight. Acute toxicity LD50 rats and mice (g/kg):>10 oral; 5~10 intramuscular and intraperitoneal injections. |
| Use | Use of anti-male hormone drugs, anti-male hormone effect. Direct competitive antagonism with androgens occurs in the prostate, and inhibits the weight of the prostate and seminal vesicles. For the treatment of prostatic hypertrophy. |
| Raw Materials | Acetic acid Bromoethane Silica gel Magnesium oxide Isopropyl acetate PARA TOLUENE Phthalic acid Estrone Hydrochloric acid Sodium borohydride 19-Norandrost-5(10)-ene-3,17-dione Triethyl orthoformate |
method 1: estrone is used as raw material. Estrone, dichloromethane, sodium hydroxide, triethylbenzyl ammonium salt (TEBA) and water, stirring at room temperature, drop dimethyl sulfate, reaction. Let it stand, divide the organic layer, and extract the water layer with dichloromethane. The organic layers are combined, washed with ammonia water, sodium hydroxide solution and hydrochloric acid, and then washed with saturated sodium chloride until neutral, dried and concentrated to obtain compound (I) with 95% yield. Compounds (I), p-toluenesulfonic acid and isopropenyl acetate (IPA) are stirred and refluxed to evaporate about 2/3 of the liquid. Cooling, ether extraction, sodium hydroxide solution washing, saturated sodium chloride washing to neutral, drying, concentration, compound (II), 85% yield. In the stirring and ice bath, to compound (II), magnesium oxide and dichloromethane solution, dropwise addition of monoperoxyphthalic acid ether solution, reaction. Filter out the solid, wash with Na2S2O3 solution, sodium hydroxide solution and saturated sodium chloride solution, dry and concentrate to obtain compound (Ⅲ) with 64% yield. At room temperature and under stirring, the mixture of ice ethanol and sulfuric acid is added dropwise to the glacial acetic acid solution of compound (III) to react. Add water and extract with dichloromethane. The extract was washed with sodium hydroxide solution and saturated sodium chloride solution until neutral, dried and concentrated to obtain compound (Ⅳ) with 74% yield. The methanol solution of compound (Ⅳ) and 5% potassium hydroxide is stirred at 40 ℃ and then refluxed. Cooling, acidification to Ph value <5. The precipitate was filtered out, the filtrate was concentrated, and the compound (V) was obtained by silica gel column chromatography with 79% yield. Under stirring, add bromoethane dropwise to the tetrahydrofuran solution of magnesium and a little iodine. The prepared ethyl magnesium bromide Grignard reagent is dropped into the tetrahydrofuran solution of compound (V) and reacted. Add ammonium chloride solution to separate the organic layer, and the water layer is extracted with ethyl acetate. The organic layers are combined, saturated sodium chloride is washed to neutral, dried and concentrated to obtain compound (Ⅵ) with 78% yield. Compound (Ⅵ), p-toluenesulfonic acid and glacial acetic acid, stirring and reflux. Pour into water, extract ether, wash water and saturated sodium chloride solution, dry, concentrate after silica gel column chromatography, obtain (VII), the yield is 37%. Compound (VII), sodium borohydride and methanol, react at room temperature. Pouring into water, the precipitated solid is compound (Ⅷ) with 90% yield. At -50 ℃, liquid ammonia is introduced into the tetrahydrofuran solution of compound (Ⅷ), and lithium is slowly added under stirring to react. Drop in ethanol, remove cooling, liquid ammonia volatilization. Add water, extract ether, dry, concentrate until dry. Separation was made by the preparation thin layer to obtain Oshondoron with 20% yield, ether recrystallization and melting point 150~152 ℃.
Method 2:3.0 g16β-ethylandrost-4-ene-3, 17-dione dissolved in 150ml dioxane, adding 15g ethyl orthoformate and 0.1g p-toluenesulfonic acid, and then stirring at room temperature for 2h. The reaction solution was poured into 300ml of 5% sodium bicarbonate aqueous solution, and the aqueous solution was extracted with ether. The ether extract is washed, dried, and concentrated to obtain the crude 3-ethoxy -16 β-ethylandrost-3, 5-diene -17-one. After recrystallization with ether, 3.0g of product is obtained with melting point 114~115 ℃.
3-ethoxy -16 β-ethylandrosterone -3, 5-diene -17-one obtained above 3.0g was dissolved in 50ml methanol, and 1.5g sodium borohydride was added. After stirring at room temperature for 1.5h, the reaction solution was poured into 300ml of water. The precipitate was collected by filtration and recrystallized with diethyl ether to obtain 2.8g of 3-ethoxy -16 β-ethylandrosterone -3,5-diene -17 β-alcohol with a melting point of 131~133 ℃.
2.5g 3-ethoxy -16 β-ethylandrosterone -3, 5-diene -17 β-alcohol was dissolved in 50ml methanol, 1.2ml concentrated hydrochloric acid was added, and then stirred for 10min. The reaction liquid is poured into 250ml of water. The precipitate was collected by filtration and recrystallized with ether to obtain 2.3g of Oshendosaurus with a melting point of 152~153 ℃.
| Toxicity | LD50 in rats, mice (g/kg): >10 orally; 5-10 I .m. and I .p. (Hiraga, 1971) |
| specific rotation | D 41° (c = 1.0 in ethanol) |