Industrial process for the preparation of gamma-lactone acid 17-hydroxy-6-beta, 7-beta, 15-beta, 16-beta-bismethylene-3-oxo-17-alpha-pregn-4-ene-21-carboxylic and key intermediates for this procedure.

Industrial process for the preparation of γ-lactone of 17-hydroxy-6β acid, 7β; 15β, 16β-bismethylene-3-oxo-17α-pregn-4-ene-21-carboxylic acid of formula (I), ** (See formula) ** obtained from the known 15α-hydroxyandrost-4-ene-3,17-dione of formula (III), wherein the 15α-hydroxyandrost-4-ene-3,17-dione of formula (III ) ** (See formula) ** it is esterified on the hydroxy in position 15 with a reactive derivative of an alkanoic acid (C1-6) to produce 15α-aciloxiandrost-4-ene-3,17-dione of general formula (IV), ** (See formula) ** wherein R represents a hydrogen atom or an alkyl group of 1-5 carbon atoms, and said compound of general formula (IV) is reacted, in the presence of an acidic catalyst with a trialkyl orthoformate having 1-4 carbon atoms in the alkyl parts, to produce 15α-acyloxy-3-alcoxiandrosta-3,5-diene-17-one of general formula (V), * * (See formula) ** in which R is my smo meaning as defined above and R1 represents an alkyl group of 1-4 carbon atoms, said compound of general formula (V) is reacted with methylide trimethylsulfoxonium prepared in situ in dimethyl sulfoxide from a trimethylsulfoxonium salt and alkali metal hydroxide, to produce the 15β, 16β-methylene-3-alcoxiandrosta-3,5-diene-17-one of general formula (VI), ** (See formula) ** wherein R1 has the same meaning defined above, said compound of general formula (VI) is reacted in the presence of lithium metal with 2- (2-bromoethyl) -1,3-dioxolane or a 2- (2-bromoethyl) -dialcoxi acetal having 1-4 carbon atoms in the alkoxy part, to produce cyclic 1,2-ethanediyl acetal of 17-hydroxy-15β, 16β-methylene-3-alkoxy-17α-pregna-3,5-diene-21- dialcoxiacetal carboxaldehyde or 17-hydroxy-15β, 16β-methylene-3-alkoxy-17α-pregna-3,5-diene-21-carboxaldehyde of general formula (VII), ** (See formula) ** in which R1 has the same meaning as defined above and R2 and R3 represent an alkyl group of 1-4 carbon atoms or form a 1,2-ethylene group together, and said compound of general formula (VII) is oxidized with chloranil (2.3 , 5,6-tetrachloro-2,5-cyclohexadiene-1,4-dione) to form cyclic 1,2- ethanediyl acetal of 17-hydroxy-15β, 16β-methylene-3-oxo-17α-pregna-4, 6-diene-21-carboxaldehyde or dialcoxiacetal of 17α-hydroxy-15β, 16β-methylene-3-oxo-17α-pregna-4,6-diene-21-carboxaldehyde of general formula (VIII), ** (See formula) ** wherein R2 and R3 have the same meaning as defined above, said compound of general formula (VIII) a) is cyclized in acidic medium to form 15β, 16β-methylene-3-oxo-androsta-4,6-diene- [ 17 (β-1) spiro-5 '] - perhydrofuran-2'ξ-ol alkyl ether of general formula (IX), ** (See formula) ** wherein R4 represents a methyl, ethyl or propyl and the bond ~ it represents α or β configuration, and said compound of formula (IX) is subjected to REACTION n with methylide trimethylsulfoxonium prepared in situ in dimethyl sulfoxide from a trimethylsulfoxonium salt and an alkali metal hydroxide, or b) is reacted with methylide trimethylsulfoxonium prepared in situ in dimethyl sulfoxide from a trimethylsulfoxonium salt and an alkali metal hydroxide to produce a bismethylene of general formula (IXa) ** derivative (see formula) ** wherein R2 and R3 have the same meaning defined above and the ~ bond represents α or β configuration, and said it compound of formula (IXa) is cyclized in an acidic medium and then, after the mixture of 6ξ, 7ξ; 15β, 16β-bismethylene-3-oxo-androst-4-ene- [17 (β-1) spiro-5 '] -perhidrofurano 2'ξ-ol-alkyl ether of general formula (X) obtained at the end in any of the sequences of the above alternative step, ** (See formula) ** wherein R4 represents a methyl group, ethyl or propyl and the bond ~ represents α or β configuration, ISOM ero 6β, 7β is separated by chromatography and oxidized with Jones reagent to produce drospirenone, or the 6ξ mixture, 7ξ; 15β, 16β-bismethylene-3-oxoandrost-4-ene- [17 (β-1) spiro-5 '] -perhidrofurano 2'ξ-ol-alkyl ether of general formula (X) obtained at the end in any of the sequences of the above alternative step, in which R4 represents a methyl, ethyl or propyl and the bond ~ represents the α or β configuration, is oxidized with Jones reagent to produce 6ξ, 7ξ; 15β, 16β-bismethylene-3-oxoandrost-4-ene- [17 (β-1) spiro-5 '] - perhydrofuran-2'-one (γ-lactone of 17-hydroxy-6ξ acid, 7ξ; 15β, 16β-bismethylene-3-oxo-17α-pregn-4-ene-21-carboxylic acid) of general formula (XI), ** (See formula) * * wherein the bond ~ represents the α configuration or β, and from this isomeric mixture the isomer 6β, 7β is isolated, and if desired the drospirenone of formula (I) obtained by any one of the synthetic routes above is purified by cryst izing. ** (See formula) **