Patent GB-1472922-A (GB)
Title: Pregnanoic acid derivatives
IPC: A61K31/67
Filed: 1974-04-11
Abstract: 1472922 20-Keto-21-oic acids of the pregnane series SCHERING AG 11 April 1974 [14 April 1973 (3)] 15988/74 Heading C2U [Also in Division A5] Novel steroids of the formula wherein X is H, halogen or CH 3 ; Y is H or halogen; Z is carbonyl or (#-alkanoyloxy)- methylene, and when Y is H, may also be methylene; R 1  is H or CH 3 ; R 2  is H, alkali metal or an optionally substituted hydrocarbon group; and -A-B- is -CH = CH- or -CCl = CH- and, when X, Y and R 1  are not all H simultaneously, may also be -CH 2 -CH 2 -, are prepared by (1) oxidation of the corresponding 20-ols, which may also be 11-ols in which case these must be acylated or oxidized; (2) for the 11-ones, oxidation of the corresponding 11α- or 11#-ols (which, as indicated under (1) may also be 20-ols); (3) oxidation of the corresponding 21-ols or their hydrates, hemi-acetals or acetals, which again may also be 11-ols in which case these must also be oxidized or acylated, preferably using as oxidizing agent an oxidizing heavy metal oxide in the presence of an alcohol and, preferably, cyanide ions; or (4) for the #<SP>1,4</SP>-compounds, dehydrogenation of the corresponding #<SP>4</SP>-compounds, which again may be 11-ols in which case they must also be oxidized or acylated. Resulting 21-esters may be hydrolysed or transesterified and resulting free acids may be salified or esterified, at any stage. Starting materials of the formula (wherein Z<SP>1</SP> is as Z or is hydroxymethylene) are prepared from the corresponding 20-keto-21- ols by stirring with cupric acetate in an alcohol for several days and then adding aqueous ammonia, to give a mixture of epimeric 20-ols. Starting materials of the formula are also prepared from the corresponding 20- keto-21-ols by reaction with lower alcohols in the presence of cupric acetate for 10-120 minutes at room temperature. 6α - Fluoro - 11α - hydroxy - 3,20 - dioxo - 16α- methyl - #<SP>1,4</SP> - pregnadien - 21 - ol prepared in this way is subsequently oxidized by the method detailed under (3) above to 6α-fluoro-11α- hydroxy - 3,20 - dioxo - 16α - methyl - #<SP>1,4</SP>- pregnadien - 21 - oic acid methyl ester and this is then oxidized to the corresponding 11-one. 6α - Fluoro - 2 - chloro - 11# - hydroxy - 3,20- dioxo - 16α - methyl - #<SP>1,4</SP> - pregnadien - 21 - oic acid methyl ester is prepared by chlorination and dehydrochlorination of the corresponding 2- unsubstituted steroid. 6α - Fluoro - 9,11# - epoxy - 3,20 - dioxo - 16α- methyl - #<SP>1,4</SP> - pregnadien - 21 - oic acid butyl ester is prepared from the corresponding 9α- chloro - 11# - ol, and is subsequently converted to the corresponding 9α-fluoro-11#-ol. 9α - Fluoro - 11#,20 - dihydroxy - 3 - oxo - 16α- methyl - #<SP>1,4</SP> - pregnadien - 21 - oic acid is prepared from 9α-fluoro-11#-17α,21-trihydroxy- 16α-methyl-#<SP>1,4</SP>-pregnadiene-3,20-dione via a mixture of 9α - fluoro - 11#,20 - dihydroxy - 3- oxo - 16α - methyl - #<SP>1,4 </SP><SP>17(20)</SP> - pregnatrien - 21 - ol and its 20-acetate. The novel steroids are anti-inflammatory agents and may be made up into pharmaceutical compositions with suitable carriers. Specifications 1,387,911 and 1,408,769 are referred to.