Patent GB-946860-A (GB)
Title: Steroid compounds
IPC: C07J75/00
Filed: 1960-03-17
Abstract: 16-alkylidene-steroids of the general formula: <FORM:0946860/C2/1> wherein R represents alkylidene, R1 represents acyl, R11 represents hydroxy or keto, and X represents hydrogen or fluorine, are prepared by reacting 16-alkylidene-steroids of the general formula: <FORM:0946860/C2/2> wherein R, R1, R11 and X have the above significance, with 2 molecules of bromine, and reacting the resulting 2,4-dibromo compound with dimethylformamide and dimethylaniline; 16-alkylidene-steroids of the general formula: <FORM:0946860/C2/3> wherein R, R11 and X have the above significance and the dotted line in the 1(2)-position represents the optional presence of a double bond, are prepared by hydrolysing the corresponding 21-acyloxy compounds; 21-esters of 16-alkylidene-steroids of the previous general formula are prepared by reacting the 21-hydroxy compounds with an acyl anhydride to form 21-acylates or with an inorganic esterifying agent to form 21-inorganic esters; 16-alkylidene-steroids of the general formula: <FORM:0946860/C2/4> wherein R, R1, R11, X and the dotted line have the above significance, are prepared by reacting 16-alkyl-steroids of the general formula: <FORM:0946860/C2/5> wherein R11 and X have the above significance, R DEG  represents a - or b -alkyl and the dotted line has the above significance, with semicarbazide and semicarbazide hydrochloride to form the corresponding 3,20-bis(semicarbazones), heating these compounds with acetic acid and acetic anhydride to form the corresponding 3,20-bis-(semicarbazone) 21-acetates, treating these compounds with hot aqueous acid to form 16-alkyl-steroids of the general formula: <FORM:0946860/C2/6> wherein R1 represents acetyl and R111 represents alkyl, and R11, X and the dotted line have the above significance, epoxidising these compounds with alkaline hydrogen peroxide, with an alkyl hydroperoxide in the presence of a base, or with an organic per-acid to form the corresponding 16a , 17a -oxido compounds, and treating these compounds, and treating these compounds with a strong mineral acid; and 16-alkylidene-steroids of the general formula: <FORM:0946860/C2/7> wherein X represents hydrogen or fluorine and R has the above significance, or the corresponding 11-keto compounds, are prepared by treating the corresponding 4-pregnenes with the dehydrogenating activity produced by growing the micro-organisms Bacillus sphaericus.  16-Alkylidene-hydrocortisone is prepared by reacting 16-alkylidene-3a -(hydroxy or acyloxy)-17a -hydroxy-11, 20-diketo-pregnane with bromine to form 16a -alkylidene-21-bromo-3a -(hydroxy or acyloxy)-17a -hydroxy-11, 20-diketo-pregnane, treating this compound with potassium iodide and potassium acetate to form 16-alkylidene-3a -(hydroxy or acyloxy)-17a -hydroxy-11,20-diketo-21-acetoxy-pregnane, oxidising this compound with sodium dichromate to form 16-alkylidene - 17a  - hydroxy - 3, 11, 20-triketo-21-acetoxy-pregnane, treating this compound with bromine to form the corresponding 4-bromo compound, treating the 4-bromo compound with semicarbazide hydrohalide to form the 3-semi-carbazone of 16-alkylidene-17a -hydroxy-3, 11, 20-triketo-21-acetoxy-4-pregnene, treating this compound with acetic and pyruvic acid to form 16-alkylidene - 17a  - hydroxy - 3, 11, 20-triketo-21-acetoxy-4-pregnene, hydrolysing this compound to form the corresponding 21-hydroxy compound, converting the 21-hydroxy compound to the 3,20-disemicarbazone of 16-alkylidene-17a , 21 - dihydroxy-4-pregnene-3, 11, 20-trione, reducing this compound with sodium borohydride to form the corresponding 11 b , 17a , 21-trihydroxy compound, and removing the semicarbazone groups at the 3- and 20-positions with pyruvic acid in aqueous acetic acid. 16-Alkylidene-3a , 17a -dihydroxy-11, 20-diketo-pregnane and the 3-acylate thereof are prepared by reacting 3a -acetoxy-11, 20-diketo-16-pregnene with a diazoalkane to form 16a , 17a -alkyleneazo-3a -acetoxy-11,20-diketo-pregnane, heating this compound to form 16-alkyl-3a -acetoxy-11, 20-diketo-16-pregnene, epoxidising this compound to form 16b -alkyl-16a , 17a -epoxy-3a -hydroxy-11, 20-diketo-pregnane, acetylating this compound to form the corresponding 3a -acetoxy compound, treating the 3a -acetoxy compound with hydrogen bromide in acetic acid to form 16 - alkylidene - 3a  - acetoxy -17a -hydroxy-11,20-diketo-pregnane and hydrolysing to the corresponding 3-hydroxy compound and, if necessary, 3-acylating as required.  Pharmaceutical compositions, which have anti-inflammatory activity and which may be administered orally, parenterally or topically, contain as the active ingredient a 16-alkylidene-steroid of the first general formula above. They may take the form of tablets, powders, capsules, elixirs, syrups, injection solutions or ointments.