Patent GB-589282-A (GB)
Title: Process for the degradation of steroid compounds
IPC: C07J9/00
Filed: 1943-08-18
Abstract: The 17-side chain of steroid compounds is shortened by treating a steroid which has in the 17-position a side chain of the form <FORM:0589282/IV/1> where R1 and R11 represent hydrogen, or aliphatic, aromatic or hydroaromatic residues and n is 1 or 2, with a carboxylic acid amide, imide or arylamide halogenated on the nitrogen, then reacting the halogenated product with a dehalogenating agent and finally oxidizing the diene so formed. If desired, any nuclear double bonds or sensitive substituents may be protected during any or all of the above reactions.  Such protection is preferably carried out in the case of double bonds by saturation with hydrogen halide, in the case of hydroxyl groups by esterification or etherification, and in the case of free keto groups by the formation of acetals.  It is possible to retain the nuclear double bond protection by forming the conjugated double bond under conditions which do not affect the nuclear double bonds, such as by simple heating, or they may be regenerated at the same time as the conjugated double bond is formed when this is done by the action of agents splitting off hydrogen halide. Agents mentioned for this purpose are tertiary amines such as pyridine, collidine, quinoline or dimethylaniline, hydroxides or carbonates of alkalies or alkaline earths, or salts of carboxylic acids, or alcohols or phenols.  The conjugated bond containing compounds thus formed are oxidized. Agents mentioned are chromic acid, permanganates, ozone and peroxides.  The unsaturated compounds which form the starting materials for the process of this invention are prepared from steroid carboxylic acids having in the 17-position a residue <FORM:0589282/IV/2> or from ketones having in the 17-position a residue <FORM:0589282/IV/3> by the action of an organo-magnesium or other organo metallic compound, followed by the direct or indirect splitting off of water.  Materials of the above kinds which are mentioned include cholic acid, desoxycholic acid, chenodesoxycholic acid, hyodesoxycholic acid, lithocholic acid, cholanic acid, allocholanic acid, ursocholenic acid, D 5-3-oxy cholenic acid, D 7-3 : 12-dioxycholenic acid, apocholic acid, norcholestane-3-ol-25-one, and D 5-norcholestene-3-ol-25-one.  In examples: (1) D 23-3a  : 12-diacetoxy-24 : 24-diphenyl cholene is treated with N-bromo-succinimide in carbon tetrachloride solution, treated with pyridine, the pyridinium salt sublimed and the diene so formed oxidized with ozone.  The 3a -oxy-12-acetoxy-pregnane-20-one so formed is isolated by means of trimethyl ammonium acetic acid hydrazide; (2) D 23 - 3a  : 12 - diacetoxy - 24 : 24 - diphenyl cholene is treated as in example (1), but using collidine as the base and chromic acid as the oxidizing agent to form 3a -oxy-12-acetoxypregnane - 20 - one.  Instead of the 24 : 24-diphenyl compound the corresponding 24 : 24-24 : 24 - dimethyl - choladiene - 3 - a  acetate is treated in the form of its hydrochloride with N-bromosuccinimide, then with collidine, and the diene oxidized with chromic acid to form progesterone.  D 5,23-24 : 24-Dimethyl-choladiene-3-ol-acetate is prepared by a Grignard reaction from magnesium methyl bromide and D 5-3-oxycholenic acid methyl ester, with subsequent mono-esterification with acetic anhydride.  D 4 : 23 - 24 : 24 - Dimethyl-choladiene - 3 - one is prepared from D 5, 23 - 3 - oxy - 24 - dimethyl - choladiene by treatment with aluminium isopropylate in toluene and cyclohexanone. D 5 - 3 - Benzoxy - 24 - isopropylidene - cholene is prepared by a Grignard reaction from methyl magnesium bromide and D 5-3-oxynorcholestene - 25 - one, the D 5 - 3 : 25 - dioxy - cholestene so obtained being converted into its monoacetate, water eliminated by treatment with phosphorus pentoxide, and the D 5-3-acetoxy-24-isopropylidene-cholene finally benzoylated with benzoyl chloride in pyridine.  D 5 - 3 - Benzoxy - 24 - ethylidene - cholene is prepared from D 5-3-benzoxy-norcholestene-25-one by the action of aluminium isopropylate in isopropyl alcohol followed by the elimination of water by phosphorus pentoxide.  Samples have been furnished under Sect. 2 (5) of the Acts of (1) 3-a -oxy-12-acetoxy-pregnane-20-one prepared by the action of N-bromosuccinimide on D 23-3a  : 12-diacetoxy-24 : 24-diphenyl cholene followed by treatment with dimethylaniline to form D 20, 23-3a  : 12-diacetoxy-24 : 24-diphenylcholadiene which is converted into its 12-monoacetate after being oxidized with chromium trioxide in glacial acetic acid; (2) 12-acetoxy-pregnane-3 : 20-dione prepared by oxidizing with chromium trioxide the D 20, 23-3a  : 12 - diacetoxy - 24 : 24-diphenyl choladiene obtained as in sample (1); (3) D 20, 23-3a -oxy-12-acetoxy-24 : 24-diphenyl choladiene is prepared by treatment of D 23-3a  : 12-diacetoxy-24 : 24-diphenyl-cholene with N-bromoacetamide in carbon tetrachloride solution followed by a working-up process as described under sample (1); (4) D 20, 23-3a -oxy-12-acetoxy-24 : 24-diphenyl-choladiene is prepared by treatment of D 23-3a  : 12-diacetoxy-24 : 24-diphenylcholene with N-bromo-2 : 4 : 6-tribromo-acetanilide followed by a working-up process as described under sample (1).