Patent GB-517942-A (GB)
Title: Manufacture of derivatives of the saturated and unsaturated cyclopentanopolyhydrophenanthrene series
IPC: C07J1/00
Filed: 1938-08-11
Abstract: 517,942. Sex hormones. SOC. OF CHEMICAL INDUSTRY IN BASLE. Aug. 11, 1938, Nos. 23710 and 23711. Convention dates, Aug. 12, 1937, and July 15, 1938. [Class 2 (iii)] Derivatives of the saturated or unsaturated cyclopentanopolyhydrophenanthrene series are prepared by reacting compounds of this series containing an ethylene linkage in the sidechain with an agent capable of adding water or acid to this linkage. The parent materials may be derived from androsterones, dehydroandrosterones, androstene-diones, dihydrotestosterones, oestrone, hexahydro-oestrone, equilin, equilenin, pregnenolones, progesterone or their enol derivatives. The ethylene linkage may be semicyclic to the nucleus or entirely in the sidechain. As suitable acids are mentioned sulphuric, acetic, propianic, benzoic and hydrohalogen acids. The addition is preformed as described in Houben-Weyl, " Methoden der organischen Chemic," Vol. 2, page 974 and 979 and Vol. 3, page 99. Compounds having free or esterified hydroxyl groups are obtained, the latter of which may be re-esterified and/or hydrolysed. During the course of the process free secondary carbinol groups may be oxidised to cyclic keto-groups by the usual methods, free carbinol groups in the side-chain being protected by etherification or esterification and nuclear double bonds being protected by addition of halogen or hydrogen halide. After oxidation the nuclear double bonds may be restored by the elimination of halogen or hydrogen halide and if a double bond is in #-#- position to a newly produced keto-group, #-# unsaturated ketones are obtained by splitting off the halogen in neutral solutions or alpha-# unsaturated ketones by splitting off the halogen in acid or basic medium. In the examples (1) 17-ethenyl-testosterone on reaction with sulphurous acid and subsequent hydrolysis yields #<4>:<5>-pregnene-17:20-diol-3-ones. If 17-ethenylandrostane-diol is used, epi-allo-pregnane-triol- (3:17:20) is obtained ; (2) 17-ethenyl-testosterone on reaction with hydrochloric acid and subsequent hydrolysis yields #<4>:<5>-pregnene- 17:20-diol-3-one; (3) #<5>:<5>-17-ethenyl-androstene-3:17-diol-diacetate with acetic acid yields <5>:<6>-pregnene-3:17:20-triol-triacetate which on hydrolysis gives #<5>:<6>-pregnene-3:17:20-triol. There is also mentioned the bromination in the 5:6-position of #<5>:<6>-17-ethenyl-androstene-diol- (3:17), followed by addition of hydrogen halide to the vinyl group, oxidation of the 3-carbinol group to keto, splitting off bromine and subsequent hydrolysis of the side-chain to yield #<4>:<5>-pregnene-17:20-diol-3-one. The products are useful in therapy. The parent ethylene compounds are prepared by the action of metal salts of acetylene or mono-substituted acetylene on keto-compounds of the cyclopentanopolyhydrophenanthrene series with subsequent partial hydrogenation, or by the action of other unsaturated organo-metallic compounds such as vinyl magnesium halide in these ketones. The Specification as open to inspection under Sect. 91 includes also the application of the process of the present invention to cyclopentanopolyhydrophenanthrene compounds containing several ethylene linkages. This subject-matter does not appear in the Specification as accepted.