Patent GB-623586-A (GB)
Title: Manufacture of derivatives of the cyclopentanopolyhydrophenanthrene series
IPC: C07J7/00
Filed: 1946-11-25
Abstract: 14-Hydroxy compounds of the cyclopentanopolyhydrophenanthrene series are manufactured by subjecting a 14 : 15-oxido-compound of the said series to reductive splitting, e.g. by treatment with hydrogen in the presence of a solvent or diluent and a metallic catalyst such as platinum, palladium, nickel or copper, or by means of nascent hydrogen, such as that produced by the reaction of an alkali metal or an amalgam thereof with an alcohol, water or a moist solvent, or of an alcoholate such as aluminium or magnesium alcoholate with a secondary alcohol, or of metal or a metal salt (e.g. zinc, stannous chloride or iron) with an organic or inorganic acid, or by an electrolytic or biochemical method, or by the addition of organo-metallic compounds (e.g. organo-magnesium halides) or of hydrocyanic acid (where the organic residue of the organo-metallic compound, or a cyano group, simultaneously enters the 15-position). The products are useful as therapeutic agents or intermediates therefor.  Preferred starting materials are those which contain in the 17-position a free or esterified carboxyl group, a free or esterified hydroxyacetyl group, an acyl or lactone group or any other aliphatic, alicyclic, heterocyclic or aromatic residue substituted in any desired manner, and which advantageously contain also a double bond starting at the 16-carbon atom (which is simultaneously reduced).  Examples describe the reduction of: (1) D 16-3b -acetoxy-14 : 15 - oxido - aetio - allo - cholenic acid methyl ester; (2) 3a  : 12a  - diacetoxy - 14 : 15 - oxido - cholanic acid methyl ester; (3) 3b -acetoxy-14 : 15 - oxido - 17 - iso - aetio - allo - cholanic acid methylester; (4) D 16-3b -acetoxy - or D 16-3b  : 21-diacetoxy - 14 : 15 - oxido - 20 - keto - allo - pregnene (with simultaneous reduction of the 20-keto group, which is then re-formed by oxidation with chromium trioxide and glacial acetic acid); (5) and (6) the starting materials of (4) (without reduction of the keto group).  Other starting materials specified are 3 : 12-dihydroxy - 14 : 15-oxido-cholanic and -17-isocholanic acids and the oxides of b -ergostenols and b -cholestenols.  14 : 15-Oxido-compounds of the cyclopentanoperhydrophenanthrene series are obtainable by oxidation of the corresponding 14 : 15-unsaturated derivatives (e.g. D 14 : 16-3b -acetoxy-aetio-allo-choladienic acid methyl ester, D 14-3a  : 12a -diacetoxy-cholenic acid methyl ester, or D 14 : 16 - 3b  - acetoxy- or D 14 : 16 - 3b  : 21 - diacetoxy-20-keto-allo-pregnadiene) by means of per-acids, e.g. peracetic, perbenzoic or monoperphthalic acid, or by splitting off hydrogen halide from the halogenhydrins of the 14 : 15-unsaturated compounds.  3b  - Acetoxy - 14 : 15 - oxido - 17 - iso - aetio - allo-cholanic acid methyl ester is obtainable by partial hydrogenation of D 16-3b -acetoxy-14 : 15-oxido-aetio-allo-cholenic acid methyl ester.  D 14 : 16-3b  - acetoxy - aetio - allo - cholodienic acid methyl ester is obtainable from D 16-3b -acetoxy-aetio-allo-cholenic acid methyl ester by bromination with bromosuccinimide, boiling with pyridine and reacetylating.  D 14 : 16 - 3b  - Acetoxy- and D 14 : 16 - 3b  : 21-diacetoxy-20-keto-allo-pregnadiene are obtainable similarly from D 16-3b -acetoxy- and D 16-3b  : 21-diacetoxy-20-keto-allo-pregnene respectively.  D 16-3b  : 21-Diacetoxy-20-keto-allo-pregnene is obtainable by treating 3b  : 21-diacetoxy-20-keto-allo-pregnane with bromine in carbon tetrachloride and glacial acetic acid in the presence of aluminium chloride and boiling the product with pyridine. The Specification as open to inspection under Sect. 91 comprises also the application of the process of the invention to corresponding compounds of the polyhydrochrysene series and especially of the dimethylpolyhydrochrysene (D-homo-steroid) series.  Reference is made in particular to the ring-D homologues of the product of example (2) above.  This subject-matter does not appear in the Specification as accepted.