Patent GB-1247661-A (GB)
Title: NEW 9beta,10alpha-STEROIDS AND METHODS OF PRODUCING THE SAME
IPC: C07J7/00
Filed: 1967-07-11
Abstract: 1,247,661. 18 - Substituted - 9#,10α - steroids. PHILIPS GLOEILAMPENFABRIEKEN N.V. 10 Oct., 1968 [11 July, 1967; 5 June, 1968], Nos. 31785/67 and 26719/68. Heading C2U. The invention comprises compounds of formula wherein R 1  is H or 1,2-methylene; R 2  is an oxo group accompanied by #<SP>4</SP>, #<SP>1,4</SP>, #<SP>4</SP>'<SP>6</SP> or #<SP>1,4,6</SP> unsaturation, a hydroxy group accompanied by #<SP>4</SP> or #<SP>4,6</SP> unsaturation or an esterified or etherified hydroxyl group accompanied by #<SP>4</SP>, #<SP>4,6</SP> or #<SP>3</SP>'<SP>5</SP> unsaturation; R 3  is H, halo or C 1-6  alkyl; R 4  is H or 6,7-methylene; R 5  is H or a free, esterified or etherified hydroxy group; R 6  is -COCH 3 , -COCH 2 OH or -CH(OH)CH 3  or an etherified or esterified -COCH 2 OH or -CH(OH)CH 3  group; and R 7  is a C 2-3  alkyl or alkenyl group. Compounds I are prepared: (1) by hydrolysis of corresponding 3,3; 20,20-bisethylenedioxy- #<SP>5</SP> compounds to give products with R 2  = 3-oxo- #<SP>4</SP> and R 6 =COCH 3 ; (2) by 1,2-dehydrohalogenation of compounds of the above formula wherein R 1  is halo and R 2  is 3-oxo-#<SP>14</SP> or 3-oxo- #<SP>4,6</SP>; (3) by Raney nickel dehalogenation of corresponding compounds bearing a 16-halogen atom (the latter compounds being obtained from #<SP>16</SP>-compounds by epoxidation followed by hydrohalogenation); (4) by catalytic hydrogenation of compounds of the above formula wherein R 2  is 3-oxo-#<SP>4</SP>, R<SP>3</SP> is = CH 2 , = CCl 2  or = CBr 2  and R 4  is H to give the corresponding 6- methyl compounds; (5) by oxidation of corresponding 17-ethylidene compounds to give products with R 5  = OH and R 6  = COCH 3 ; and (6) by reaction of corresponding 21-halo-20-oxo compounds (obtained from 21-unsubstituted- 20-oxo compounds by the successive actions of a dialkyl oxalate, a molecular halogen and an alkali metal alkoxide) with an alkali or alkaline earth metal carboxylate to yield 21-acyloxy-20- oxo products. Compounds I are interconverted (1) by chemical or microbial 1,2-dehydrogenation; (2) by chemical 6,7-dihydrogenation; (3) by oxidative conversion of a 3-(etherified hydroxy)- #<SP>3</SP>'<SP>5</SP> compound to a 3-oxo-#<SP>4.6</SP> compound; (4) by enol-etherification or enol-esterification of a 3-oxo-#<SP>4</SP>-compound; (5) by 6-halogenation of a 3-oxo-#<SP>4</SP> compound or an enol ether or enol ester thereof; (6) by esterification or esterification of 3, 17, 20 and 21 hydroxyl groups; (7) by reacting a #<SP>1</SP>- or #<SP>6</SP>-compound with dimethylsulphoxonium methylide to give a 1,2-methylene or 6#,7#-methylene compound respectively; (8) by reduction of 3 and 20 oxo groups to hydroxy groups; (9) by oxidation of 3 and 20 hydroxy groups to oxo groups; (10) by hydrolysis of esterified and etherified hydroxyl groups; and (11) by chemical or microbial 21 -hydroxylation of 21-unsubstituted-20-oxo compounds. 3,3; 20,20 - Bis(ethylenedioxy} - 18 - ethyl- 9#,10α-pregen-5-ene (L) is prepared from 9#,10α- preg-4-ene-3,20-dione (LI) by the sequence: LI-> 20 - cyano - 20 - hydroxy - 9#,10α - pregn- 4 - en - 3 - one -> 18 - cyano - 9#,10α - pregn-4- ene - 3,20 - dione ( + 17# - iodo - 9#,10α - androst- 4 - en - 3 - one as by-product)-> 3,3; 20,20- bis(ethylenedioxy) 18 - cyano - 9#,10α - pregn - 5- ene ( + 20,20 - ethylenedioxy - 18 - cyano - 9#,10α- pregn-4-en-3-one as by-product)-> 3,3; 20,20- bis(ethylenedioxy) - 18 - iminomethyl - 9#,10α- pregn-5-ene -> 3,3; 20,20.bis(ethylenedioxy)- 18 - formyl - 9#10α - pregn - 5 - ene (LII)-> 3,3; 20,20 - bis(ethylenedioxy) - 18 - vinyl - 9#,10α- preyn-5-ene -> L. 3,3; 20,20 - Bis(ethylenedioxy) - 18 - methyl- 9#,10α-pregn-5-ene is prepared from LII. 6 - Dichloromethylene - 18 - methyl - 9#,10α- pregn-4-ene-3,20-dione is prepared from 3- ethoxy - 18 - methyl - 9#,10α - pregna - 3,5- dien - 20 - one via 6# - trichloromethyl - 18 - methyl - 9#,10α - pregn - 4 - ene -3,20-dione. 18 - Ethyl - 9#,10α,17α - pregna - 4,6 - diene- 3,20-dione is obtained as a by-product in the preparation of the corresponding 9#,10α,17#- compound by interconversion (2) above. 18 - Methyl - 9#,10α - pregna - 4,17(20) - dien- 3-one is prepared by dehydration of 18-methyl- 20-hydroxy-9#,10α.pregn-4-en-3-one. Compounds of the above formula are stated to be progestational agents, and may be made up with carriers into pharmaceutical compositions for oral and parenteral administration.