Patent GB-516445-A (GB)
Title: Manufacture of carboxylic acids of the cyclopentanopolyhydrophenanthrene series
IPC: C07J9/00
Filed: 1938-06-27
Abstract: 516,445. Cyclopentanopolyhydrophenanthrene carboxylic acids. SOC. OF CHEMICAL INDUSTRY IN BASLE. June 27, 1938, Nos. 18996 and 18997. Convention dates, June 28, 1937, and Jan. 10, 1938. [Class 2 (iii)] Carboxylic acids of the cyclopentanopolyhydrophenanthrene series are obtained by treating a compound of this series which has either a saturated or an unsaturated nucleus and has in the 17-position a side chain containing an acetylenic linkage with an agent which splits acetylene linkages with the formation of a carboxyl group. Reagents known for this purpose are described in Houben-Weyl Methoden der organischen chemie 3rd Edition, Vol. 2, page 159, and comprise ozone, chromic acid, nitric acid, a persulphate or a peroxide such as perbenzoic acid or hydrogen peroxide, advantageously in the presence of osmium tetroxide. If oxidizable substituents are present in the nucleus and in the side chains such as hydroxyl or amino groups they are preferably protected by substitution when their simultaneous oxidation is not desired. Similarly nuclear double bonds may be protected by the addition of halogen, which may be added to nuclear double bonds without , simultaneous saturation of the less reactive side chain acetylenic links. After the oxidation the protecting halogen is removed by treatment with, for example, zinc dust and acetic acid, an alkali iodide or a tertiary base such as pyridine or dimethylaniline. The carboxylic acids so obtained may be purified by recrystallization, distillation or by using their specific reactive groups such as by means of their salts. In examples (1) a chloroform solution of 3-acetoxy- 17-ethinyl androstanol-17 is treated with ozone at 0‹C. The solvent is removed, the residue treated with water and the reaction products taken up in ether. The acid fraction is extracted from the ether by alkali to give 3-acetoxy-17-oxy aetio-allocholanic acid. (2) A glacial acetic acid solution of #<5>.<6>-3 acetoxy-17-ethinyl androstenol-17 is oxidized with ozone with intermediate protection of the nuclear double bonds to give #<5>.<6>-acetoxy-17-oxy-aetiocholenic acid. (3) A glacial acetic acid solution of #<5>.<6>-3:17-diacetoxy-17-ethinyl androstene is oxidized as in example (2) to give #<5>.<6>-3:17: diacetoxy-aetiocholenic acid. (4) A carbon tetrachloride solution of #<5>.<6>-3-trans-acetoxy- 17-oxy-17-ethinyl-androstene is oxidized as in example (2) to give an acid which is then esterified with diazomethane to give #<5>.<6>-3- trans-acetoxy-17-hydroxy-aetiochlolenic acid methyl ester. Saponification of this ester yields the corresponding dihydroxy ester. The Specification as open to inspection under Sect. 91 included also the production of aldehydes and ketones by the oxidative splitting of steroid compounds which contain an unsaturated side chain, but no example of the production of these bodies was included. The unsaturated steroids included ethylenic as well as acetylenic side chain compounds. The side chains were also stated to be attached to any point on the tetracyclic necleus other than position-17. A number of more or less complex wide chains containing acetylenic and ethylenic linkages were specifically mentioned. This subjectmatter does not appear in the Specification as accepted.