GB994749A - 19-oxygenated and 19-nor-steroids and process for their manufacture - Google Patents

Abstract

The invention comprises (1) a process for the preparation of D 4-3-oxo-steroids containing a 10-CH2OH or an ester or ether thereof, a 10-CHO or a 10-COOH group wherein a D 4 - 3 - oxo - 6b ,19 - oxido - steroid or a corresponding 19,6b -hemiacetal or 19,6b -lactone of a 6b -hydroxy-steroid 19-al or 19-acid is treated with a reducing agent and any resulting D 5-3-oxo-steroid is isomerized with an acidic or basic agent to the corresponding D 4-3-oxo-steroid and, if desired, any hydroxy compound obtained is esterified, etherified and/or oxidized with a derivative of hexavalent chromium and/or any ester obtained is hydrolysed; (2) D 5-3-oxo-19-nor-steroids of the androstane or pregnane series containing in the 10-position a free, esterified or etherified hydroxymethyl group, a formyl, a carboxyl or a carbomethoxy group; (3) D 4 - 3 - oxo - 17a - ethynyl - 17b -hydroxy - 19 - nor - androstenes containing a 10-formyl, -carboxyl or -carbomethoxy group; (4) D 4 - 3,20 - dioxo - 17a - acetoxy - 19 - nor-pregnenes containing a 10-formyl, -carboxy or -carbomethoxy group; (5) D 4 - 3,20 - dioxo-pregnene-19-acid and its methyl ester; (6) D 4 - 3 - oxo - 19 - nor - androstenes containing a 10-hydroxymethyl, -acetoxymethyl, -formyl, -carboxyl or -carbomethoxy group and a 17b -acyloxy group derived from a carboxylic acid of 4 to 15 carbon atoms; and (7) D 5(10)-3-oxo-17b - (b - phenylpropionyloxy) - 19 - nor-androstene. The starting materials for process (1) may belong to the spirostane, androstane, pregnane, cholane, cholestane, stigmastane or cardanolide series and may contain free, ketalized or enolized oxo groups, esterified or etherified hydroxyl groups, alkyl groups or halogen atoms in one or positions of the steroid nucleus or the 17-side chain. They may also contain double bonds or oxido groups. In process (1) isomerization may accompany reduction if, for example, the reducing agent is zinc in a carboxylic anhydride. The products are 19 - hydroxy - steroids, steroid - 19-aldehydes or steroid-19-acids, prepared, respectively from 6b ,19-oxido-steroids, 19,6b -hemiacetals and 19,6b -lactones, and the 19-ols may be oxidized to the aldehydes and then the acids, or they may be etherified or they or the acids esterified. 17-Keto products may be converted to 17b - hydroxy - 17a - alkyl or alkyryl compounds. The D 4-3-oxo-19-aldehydes and 19-acids may be converted to 19-nor compounds, and if this is effected by heating in pyridine the products are predominantly D 5(10)-3-oxo-19-nor compounds which with acids yield D 4-3-oxo-19-nor-steroids. Detailed examples of all the above processes are provided. D 3,5 - 3 - ethoxy - 19 - acetoxy - 17 - oxoandrostadiene is prepared from the D 4-3-one and ethyl orthoformate. D 4 - 3 - oxo - 6b ,19 - oxido - 17b - decanoyloxy and b - phenyl - propionyloxy - androstenes are prepared by esterification of the 17b -ols. Specifications 994,746, 994,748 and 994,750 are referred to.