Patent GB-748887-A (GB)
Title: Cyclopentanophenanthrene derivatives and a method for the preparation thereof
IPC: C07J5/00
Filed: 1953-03-04
Abstract: The invention comprises (a) allopregnane-11a  : 17a  : 21-triol-3 : 20-dione and its 21-monoesters and 11 : 21-diesters; (b) the production of 21-monoesters and 11 : 21-diesters of pregnane- or especially allopregnane-11a  : 17a  : 21-triol-3 : 20-dione by treating a diester of a 16a  : 17a -oxidopregnane-3 : 11a -diol-20-one (especially of the allo series) with bromine and hydrobromic acid to form the corresponding 16 : 21-dibromo-17a -hydroxy compound, treating this with an alkali metal iodide in a lower ketone to form the corresponding 21-iodo compound, treating this with potassium acetate to form the corresponding 3 : 11a -diacyloxy-21-acetoxy - 16a  : 17a  - oxidopregnan - 20 - one, treating this with a saponifying agent to saponify it in at least the 3- and 21-positions followed by treatment with approximately one molar equivalent of an esterifying agent at low temperature to re-esterify the 21-hydroxy group only, and treating the resulting product with, in either order, an oxidizing agent to oxidize the 3-hydroxy group to a 3-keto group, and hydrobromic acid followed by a debrominating agent; (c) the production of compounds of the general formula <FORM:0748887/IV(a)/1> (wherein Y represents a 22-spirostane, 22-isospirostane, 20-ketopregnane, 20-keto-21-acyloxypregnane, 16a :17a  - oxido - 20 - ketopregnane, 16a :17a  - oxido - 20 - keto - 21 - acyloxypregnane, 17a  - hydroxy - 20 - ketopregnane or 17a  - hydroxy - 21 - keto - 21 - acyloxypregnane side chain) by selectively oxidizing the 3-hydroxy group of a corresponding 3b :11a -diol compound by means of approximately one molar equivalent of N-bromoacetamide in the presence of an organic solvent selected from tertiary lower aliphatic alcohols, tertiary amines and mixtures thereof, or (except when Y represents a 17a -hydroxy-20-ketopregnane or 17a -hydroxy - 20 - keto - 21 - acyloxypregnane side chain) by means of an aluminium alcoholate or phenolate in the presence of a hydrogen acceptor and an inert organic solvent.  In examples (1) 16a :17a  - oxidoallopregnane - 3b :11a  - diol-20-one diacetate is treated with hydrobromic acid in acetic acid and then with bromine in acetic acid or carbon tetrachloride, the product is dissolved in acetone and treated with sodium iodide and then with potassium bicarbonate and acetic acid to produce 16a :17a -oxidoallopregnane - 3b :11a :21 - triol - 20 - one triacetate, this is completely saponified by refluxing with ethanolic sodium or potassium hydroxide, the resulting triol is monoesterified in the 21-position by the action of acetic anhydride and pyridine in the cold, the 21-monoacetate is oxidized to the 3:20-dione with aluminium isopropylate and cyclohexanone in benzene, and the product is treated with hydrobromic acid in acetic acid and then refluxed with Raney nickel in acetone to produce allopregnane-11a :17a :21-triol-3:20-dione 21-monoacetate; (2) the complete saponification in (1) is replaced by saponification in the 3- and 21-positions only by refluxing with sodium bicarbonate in alcohol, and the treatment with hydrobromic acid followed by Raney nickel precedes the oxidation, which is effected with N-bromoacetamide in pyridine; the resulting allopregnane - 11a :17a :21-triol - 3:20 - dione 11:21 - diacetate may be converted to the product of (1) by saponification and selective acetylation; (3) 16a :17a -oxidoallopregnane - 3b :11a :21 - triol - 20 - one 11:21 - diacetate is oxidized to the 3:20-dione by means of chromic acid in acetic acid, or N-bromoacetamide in pyridine; or (4) by means of aluminium isopropylate and cyclohexanone in toluene; (5) 16a :17a -oxidoallopregnane - 11a :21 - diol - 3:20 - dione diacetate is treated with hydrobromic acid in acetic acid and then refluxed with Raney nickel in acetone to give the initial product of (2); (6) allopregnane - 3b :11a  - diol - 20 - one is oxidized with aluminium tert.-butylate and cyclohexanone in toluene to allopregnane-11a -ol-3:20-dione, which may be acetylated with acetic anhydride and pyridine; (7) allopregnane - 3b :11a :21 - triol - 20 - one 21 - monoacetate is oxidized with aluminium isopropylate and acetone in toluene to allopregnane-11a :21-diol - 3:20 - dione 21 - monoacetate; (8) 22-isoallospirostane - 3b :11a  - diol is oxidized with aluminium isopropylate and cyclohexanone in toluene to 22-isoallospirostan-11a -ol-3-one; (9) 16a :17a  - oxidoallopregnane - 3b :11a  - diol-20-one is oxidized with aluminium phenoxide and cyclohexanone in toluene to 16a :17a -oxidoallopregnan - 11a  - ol - 3:20 - dione; (10) 16a :17a - oxidoallopregnane - 3b :11a :21-triol - 20 - one 21 - monoacetate is oxidized with aluminium isopropylate and cyclohexanone in benzene to 16a :17a -oxidoallopregnane-11a :21 - diol - 3:20 - dione 21 - monoacetate; (11) allopregnane - 3b :11a  - diol - 20 - one is oxidized with N-bromoacetamide in pyridine to allopregnan - 11a  - ol - 3:20 - dione; (12) the 3-hydroxy group is similarly oxidized in 22-isoallospirostan - 3b :11a  - diol, allopregnane-3b :11a :21 - triol - 20 - one 21 - monoacetate, 16a :17a  - oxidoallopregnane - 3b :11a  - diol-20 - one, 16a :17a  - oxidoallopregnane-3b :11a :21 - triol - 20 - one 21 - monoacetate, allopregnane - 3b :11a :17a  - triol - 20 - one and allopregnane - 3b :11a :17a :21 - tetrol - 20-one 21 - monoacetate; (13) the pyridine in (11) and (12) is partly replaced by tert.-butanol.