Herstellung von neuen 7-Methyl-19-nor-androstadienen

摘要

1,158,332. 7α - Methyl 19 - nor - androstadienes. CIBA Ltd. 25 July, 1966 [30 July, 1965; 10 Sept., 1965; 27 June, 1966], No. 33284/66. Heading C2U. Novel steroids of the formula (wherein R is oxo or free, esterified or etherified #-OH with or without an α-aliphatic hydrocarbon group of up to 4 carbon atoms which may be substituted) are prepared from the corresponding #5'10'-steroids by bromination and dehydrobromination. In the products, a 17#-OH group may be esterified or etherified, or an esterified or etherified 17#-OH group hydrolysed; or a 17-oxo group may, after protection of the 3-oxo group, be converted to a 17α- hydrocarbyl-17#-OH grouping and the 3-keto group then liberated. The #5'10'-steroid starting materials may also be converted to the required products by microbiological 11 -hydroxylation, dehydration to the corresponding #5'01' 9'11'-steroids and treatment of these with a mineral acid, or by conversion of the 11- hydroxy compounds to sulphonic acid esters thereof, and then treatment with an alkali metal salt of a lower aliphatic carboxylic acid. #4 9 - 7α methyl - 3 - oximino 17 - oxo - 19- nor-androstadiene is prepared by reacting 3,17- dioxo-7α-methyl-#4 9-19-nor-androstadiene with HCN or a derivative thereof to convert the 17- oxo group to a cyanohydrin group, reacting the #4 9 - 7α - methyl - 3 - oxo - 17 - cyano - 17#- hydroxy-19-nor-androstadiene with hydroxylamine or a lower alkyl hydroxylamine to give #4 9 - 7α - methyl - 3 - oximino - 17 - cyano - 17#- hydroxy-19-nor-androstadiene and then saponifying this. 3 - Oxo - 7a - methyl - 17# - hydroxy - #5'10'- 19-nor-androstene is prepared by hydrolysis of 3 - methoxy - 7α - methyl - 17# - hydroxy - #2 5'10'- 19 - nor - androstadiene, prepared in turn by LiAlH 4 reduction of 7α-methyl-estrone methyl ether, to give 3-methoxy-7α-methyl- 17#-hydroxy- #1 3 5'10'-estratriene, and Birch reduction of this. 3 - Oxo - 7α,17α - dimethyl - 17# - hydroxy - #5'10'- 19-nor-androsfene is prepared by hydrolysis of 3 - methoxy - 7α,17α - dimethyl - 17# - hydroxy- #2 5'10'-19-nor-androstadiene, itself prepared from the 17-ketone. The corresponding 17α-ethynyl compounds are prepared similarly. 3 - Methoxy - 7α - methyl - 11 - hydroxy - 17- ethylenedioxy - #2 5'10' - 19 - nor - androstadiene is prepared by ketalizing 3-methoxy-7α-methyl- 17 - oxo - #1 3 5'10' 9'11' - 19 - nor - androstatetraene (prepared by methylation of the 3-ol) to give the corresponding 17-ketal, reacting this with mchloro-perbenzoic acid to give 3-methoxy-7α- methyl - 9,11 - oxido - 17 - ethylenedioxy- #1 3 5'10'-19-nor-androstratiene, and reducing this with sodium in liquid ammonia; and is converted to the 17-ketone of the invention by dehydration with POCl 3 and hydrolysis with HCI. The 7α-methyl-steroids of the invention, which are stated to possess androgenic, anabolic, antigonadotrophic and gestagenic action, may be made up into pharmaceutical and veterinary compositions with suitable carriers.