Patent GB-522066-A (GB)
Title: Method for the production of urane compounds and product thereof
IPC: C07J75/00
Filed: 1939-01-03
Abstract: 522,066. Urane compounds. PARKE, DAVIS & CO. Jan. 3, 1939, No. 144. Convention date, Jan. 3, 1938. [Class 2 (iii)] Compounds occurring in pregnancy urine having a cyclopentanopolyhydrophenanthrene structure and isomeric with pregnane compounds but differing therefrom in the spatial configuration of rings B and C and known as urane compounds are obtained by fractionally crystallizing a solution in an organic solvent of a neutral ether soluble, non-phenolic carbinol fraction of pregnancy urine. The crystallization may take place without any previous transformation of the urane compounds present in the pregnancy urine, or the compounds may be subjected to a preliminary treatment to form simple derivatives such as ketones or alcohols and derivatives thereof such as esters ethers and halides which yield said ketones or alcohols on hydrolysis. It is preferred to first submit the extract to an alkaline hydrolysis before the fractional crystallization, and then to submit the crude mixture of alcohols to acylation with a lower carboxylic acid acylating agent such as acetic anhydride. In examples (1) a non-phenolic carbinol fraction of mare's urine is hydrolyzed with sodium hydroxide, steam distilled, and extracted with benzol. The benzol is evaporated, the product taken up in ether and crystallized. The crystals are filtered, dissolved in alcohol purified with animal charcoal and fractionally crystallized. The less soluble portion being the required urane triol, and the more soluble fraction pregnane triol. (2) the urane triol isolated in example (1) is acetylated with acetic anhydride. (3) The urane triol triacetate of example (2) is hydrolyzed with potassium hydroxide to give a slightly more pure triol than that isolated in example (1). (4) The alcohol fraction in example (1) is acetylated with acetic anhydride and the triacetates fractionally crystallized, the acetate of urane triol being the more soluble fraction. (5) The neutral fraction from human pregnancy urine after removing the phenolic sex hormones, pregnanediols and epi-allopregnanolone as described in Specification 509,062 is taken up in ether, ligroin added and then decanted from the oily layer which is dissolved in acetic acid and oxidized with chromium trioxide. The ketones are removed from the product with betaine hydrochloride, and fractionally distilled. The fraction between 170-200‹C. is pure uranetrione. (6) Uranetriol is oxidized to uranetrione by chromic acid in acetic acid solution and is purified by its di-2:4-dinitrophenylhydrazone. (7) Uranetriol is treated with sodium metal in xylene without any effect on the solubility of its digitonide, thus indicating a coprostane structure. (8) Treatment of uranetrione with bromine in glacial acetic acid forms 4-bromouranetrione-3:11:20. (9) The bromo compound prepared in example (8) is debrominated by pyridine. (10) Uranetrione is reduced to the hydrocarbon urane by treatment with zinc in acetic acid solution. (11) Uranetrione is reduced to uranetriol by hydrogen in the presence of platinum oxide. This is converted to a.diacetate by acetic anhydride and oxidized to uranediol- (3:20)-one-11-diacetate. This is reduced by zinc and hydrochloric-acetic acid to the corresponding diol-3:20-diacetate. Hydrolysis with caustic soda and oxidation with chromium trioxide converts this into uranedione-3:20. (12) The filtrate from the triols in example (1) is oxidized with chromium trioxide and fractionally crystallized uranedione-3:20. The Specification as open to inspection under Sect. 91 includes also the preparation of allopregnane from allo-pregnandione by means of zinc amalgam in acetic acid solution. This subject-matter does not appear in the Specification as accepted.