Patent GB-1096762-A (GB)
Title: Processes for preparing steroids compounds and the compounds when thus prepared
IPC: A61K31/568
Filed: 1964-12-17
Abstract: The invention comprises 13b -alkyl-gon-3-ones of the general formula <FORM:1096762/C2/1> wherein Y represents an alkyl group having from 2-18 carbon atoms and A and B together form the oxygen atom of a keto group in which case there is a 5(10) double bond or A is a group OX wherein X is a hydrogen atom or an acyl group derived from a lower organic carboxylic acid having from 1-10 carbon atoms and B is an unsaturated aliphatic hydrocarbon radical having from 2-4 carbon atoms in which case there is a 4(5)- or a 5(10)-double bond and a process for the preparation of a 13b -alkyl-steroid (wherein the alkyl group contains from 2-18 carbon atoms) comprising the steps of (i) condensing a 5-oxo-6-heptenoic acid alkyl ester (wherein the alkyl group contains from 1-10 carbon atoms) with a 1,3-dioxo-2-alkylcyclopentane (wherein the alkyl group contains from 2-18 carbon atoms) in the presence of an alkaline condensation agent, and effecting cyclization and saponification of the condensation product by reaction with an acid or acid/base couple so as to form a racemic mixture of the corresponding 1,5 - dioxo - 4 - (21 - carboxy-ethyl) - 7a - alkyl - 5,6,7,7a - tetrahydroindane, (ii) resolving the racemic mixture by reaction with an optically active base into the dextrorotatory and laevorotatory enantiomorphs, and reacting the material dextrorotatory in acetone with a mixed hydride so as to form, by reduction of the keto group at 1-position, the corresponding 1b  - hydroxy - 5 - oxo - 4 - (21 - carboxyethyl) - 7ab - alkyl - 5,6,7,7a - tetrahydroindane, (iii) subjecting this product to catalytic hydrogenation so as to form the corresponding 1b  - hydroxy - 5 - oxo - 4 - (21 - carboxyethyl)-7ab  - alkyl - 3aa ,4b ,5,6,7,7a - hexahydroindane, (iv) reacting this material with an acylating agent so as to form the d -lactone of the corresponding 1b -acyloxy-4-(21-carboxyethyl)-5-hydroxy - 7ab  - alkyl - 3aa ,4b ,7,7a - tetrahydroindane, (v) reacting the d -lactone with a ketal of a 4-oxopentyl magnesium halide, reacting the product with an alkali-metal base and then subjecting the resulting material to acid hydrolysis, so as to form the corresponding 17b -hydroxy - 13b  - alkyl - 4,5 - seco - gon - 9 - ene-3,5 - dione, (vi) cyclizing this 4,5-seco-gonene in the presence of an alkali-metal condensation agent so as to form the corresponding 17b -hydroxy - 13b  - alkyl - gona - 4,9 - dien - 3 - one, (vii) reducing this 17b -hydroxy-gonadiene with an alkali metal or an alkaline earth metal in liquid ammonia in the presence of a proton donor so as to form the corresponding 17b -hydroxy - 13b  - alkyl - gon - 5(10 - en - 3 - one, (viii) reacting this 17b -hydroxy-gon-3-one with an oxidizing agent so as to form the corresponding gon-3,17-dione, (ix) reacting this product with an alkali-metal derivative of an unsaturated aliphatic hydrocarbon so as to form the corresponding 17a -unsaturated aliphatic-17b  - hydroxy - 13b  - alkyl - gon - 5(10) - en - 3-one, and (x) subjecting this material to isomerization so as to form the corresponding 17a -unsaturated aliphatic - 17b  - hydroxy - 13b  - alkyl-gon-4-en-3-one.  Pharmaceutical compositions having progestative activity and containing the above compounds are administered, orally, parenterally or rectally.