GB1277265A - 6-substituted-13-polycarbonalkyl-18,19-dinorpregn-4-en-3-ones - Google Patents

Abstract

1277265 6 - Substituted - 13 - polycarbonalkyl - 18,19 - dinorpregn - 4 - en - 3 - ones AMERICAN HOME PRODUCTS CORP 30 July 1969 [30 July 1968 19 May 1969] 38168/69 Heading C2U Novel steroids having in rings C and D the structure (wherein R is C 2-6 alkyl; X is CO or CH(OR<SP>1</SP>) in which R<SP>1</SP> is H or C 2-7 alkanoyl; and Y is H, OH or C 2-7 alkanoyloxy) and in rings A and B the structure wherein C 6 -C 7 is a divalent radical of one of the structures wherein Z is Cl, Br or F and Z<SP>1</SP> is Cl or Br, provided that a 6α-methyl substituent is not present when X is CO and Y is H, are prepared and interconverted by the following processes (a) hydrogenating a 6-methylene compound to give a 6α-methyl compound; (b) rearranging a 6- methylene compound to give a 6-methyl-#<SP>4,6</SP>- compound; (c) halogenating a #<SP>3,5</SP>-3-enol ester (alkanoate) to give a 6α-(chloro or bromo)- #<SP>4</SP> compound; (d) dehydrogenating a #<SP>4</SP>-6α- halo compound to give a #<SP>4,6</SP>-6-halo compound; (e) reacting a #<SP>4</SP>-6α,7α-epoxide with a hydrogen halide to give a #<SP>4,6</SP>-6-halo compound; (f) partially hydrolysing a compound of the formula (where Z<SP>2</SP> is CH 3 , Cl or Br and R<SP>2</SP> is C 1-6 alkyl) to give a #<SP>4</SP> - 6 - methyl, chloro or bromo - 17α- alkanoyloxy product, the starting material being prepared by acylation of a #<SP>4</SP>-3-one followed by interconversions in the 17-side chain when required; (g) hydrolysing a 3-alkoxy-6-hydroxymethyl - #<SP>3,5</SP> - compound to give a 6 - methylene- #<SP>4</SP>-compound; (h) hydrolysing a compound of the formula (where K is a protected oxo group which in conjunction with unsaturation in rings A and/or B is hydrolysable by acid to a #<SP>4</SP>-3-ketone, and X is as defined above or may be a protected carbonyl or hydroxymethylene group) to give a #<SP>4</SP>-6-methyl product; this process and the preparation of starting materials therefor is illustrated as follows or as follows Compounds (h). may be oxidized to 20-ones prior to hydrolysis. Compounds (o) may be acylated; or (i) isomerizing a #<SP>5(10)</SP>-3-keto-6-R<SP>3</SP>-compound (where R<SP>3</SP> is α-or #-CH 3 , α-Cl or α-Br) to give a corresponding #<SP>4</SP>-compound. #<SP>4</SP>-6-Methylene compounds may be obtained as follows (other 3-alkoxy-compounds may also be used) or as follows 20-Substituents may be interconverted. All products may be resolved d-steroids or racemates. Starting materials of the formula are prepared from corresponding #<SP>2</SP>'<SP>5(10)</SP>-3-enol ethers byhydrolysis and acylation; 20-ketals may be used as starting materials in this process. Epoxide starting materials are prepared as follows 13 - Polycarbonalkyl - 6α - methyl - 18,19- dinorpregn - 4 - ene - 3,20 - diones are prepared by oxidation of the corresponding 20-ols. The novel steroids, except the 6-methylene compounds, have progestational and antiestrogenic activity, and may be made up into pharmaceutical compositions with suitable carriers.