| 摘要 |
Pregnenes minimally possessing 3,20-diketo-4-dehydro - 16a - lower alkyl - 17a - hydroxy-21-hydroxy or lower alkanoyloxy substituents are prepared by chlorinating 3-acylates of 5(6),16-pregnadien-3-ol-20-ones to give the corresponding 5,6-dichloro-16-pregnenes, intro ducing into these the 16a -lower alkyl group, the 17a - hydroxy group, the 21 - hydroxy or -alkanoyloxy group and the 3-keto group by known methods and thereafter dehalogenating the product. The chlorination, which is effected in a non-aqueous inert organic solvent, may utilize a substantially equimolar quantity of chlorine to give the 5,6-dichloro-16-pregnenes direct or it may utilize a molar equivalent excess of chlorine to give a reaction product containing a quantity of 5,6,16,17-tetrachloro-pregnane which is thereafter partially dehalo genated, for example by treatment with zinc and acetic acid at below 40 DEG C. or by treatment with chromous chloride. The lower alkyl group is defined as having at most 3 carbon atoms and the lower alkanoyl at most 7. The steroids may also possess an 11a or b -hydroxy- or an 11-keto-substituent. Preferably, the 5,6-dichloro com pound is reacted with a lower alkyl magnesium halide and then with an acyl halide to give a 5,6 - dichloro - 16a - alkyl - 17(20) - pregnen-3,20-diol 3,20-diacylate, this is reacted with hydrogen peroxide or peracetic acid to give the 17,20-epoxide, this is hydrolysed to a 5,6-dichloro -16a - alkyl - pregnan -3,17a - diol-20-one 3-acylate, this is 21-brominated and the product treated with an alkali metal alkanoate followed, if desired, by hydrolysis, to give a 5,6 - dichloro - 16a - alkyl - pregnane - 3,17a ,21-triol -20 - one 3 - acylate or 3,21 - diacylate, this is hydrolysed in the 3-position and then oxidized to give a 5,6-dichloro-16a -alkyl-preg nane - 17a ,21 - diol - 3,20 - dione or a 21-acylate thereof and this is converted to the desired product by refluxing with zinc and acetic acid. Examples are given.
|
