http://rdf.ncbi.nlm.nih.gov/pubchem/patent/GB-1004184-A
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_dc2f7134efa50484bb359fda73782848 |
| classificationCPCAdditional | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/Y02P20-55 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J75-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J71-00 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J75-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J71-00 |
| filingDate | 1961-12-14-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 1965-09-08-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | GB-1004184-A |
| titleOfInvention | Cyclosemiacetals of 18-oxo-11ª‰-hydroxy-pregnanes and process for their manufacture |
| abstract | The invention comprises (1) a process for the preparation of an 11b ,18-oxido-18,20-dihydroxy compound of the pregnane series or an ether or ester thereof wherein the 18,20-lactone of an 11 - oxo - 20 - hydroxy - pregnane - 18 - acid is treated with a complex aluminium hydride; (2) a 21-unsubstituted 11b ,18-oxido-18,20-dihydroxy compound of the pregnane series or an 18-ether thereof; (3) an 11b ,18-oxido-18,20-diacyloxy compound of the pregnane series or a corresponding free 18-hydroxy compound or an 18-ether thereof; and (4) D 4-3,20-dioxo-11b ,18-oxido - 18 - tetrahydropyranyloxy - pregnane or a ketal or enol ether thereof. Process (1) may be combined with the further steps of acylating the product with a reactive derivative of a carboxylic or sulphonic acid and, if desired, hydrolysing the 18,20-diacylate so formed by a mild acidic treatment or with water to give a 20-mono-acylate which may then be etherified in the 18-position and the resulting 18-ether-20-acylate hydrolysed with an alkali or with lithium aluminium hydride and then the resulting 20-ol oxidized to a 20-one, and, if desired, the free 18-hydroxy group again liberated. Other oxo groups in the starting material are also reduced in process (1) unless they are protected by ketalization or enol ether formation, and esterified hydroxy groups are converted to free hydroxy groups. The products of (1) or acylates thereof are converted by acids such as acetic acid to 11b ,18; 18,20-bis-oxido compounds. Other free hydroxy groups may be esterified in the optional acylation stage, and ketal groups hydrolysed in the acid treatments. Starting materials for process (1) may contain etherified or esterified hydroxy groups, free or functionally converted oxo groups, alkyl groups or halogen atoms as substituents in the steroid nucleus or the 17-side chain, and they may also contain double bonds. In the products, particularly the 18-ethers, a 21-hydroxyl group may be introduced by oxalic ester condensation, iodination, and treatment with potassium acetate e.g. compounds (4), after removal of the protecting groups, give 21-acetyl-aldosterone. Examples illustrate the above processes. In one of them reaction of D 5-3-ethylenedioxy-11b ,18 - oxido - 18 - hydroxy - 20 - b - acetoxy-pregnene with methyl orthoformate gives D 3,5 - 3 - methoxy - 11b ,18 - oxido - 18 - methoxy - 20b - acetoxy - pregnadiene; in another a by-product of the heating of D 5-3-ethylene-dioxy - 11b ,18 - oxido - 18,20b - diacetoxy - pregnene with acetic acid is D 4-3-oxo-11b -hydroxy-18,20b - diacetoxy - pregnene, and the main product, D 4 - 3 - oxo - 11b ,18 - oxido - 18 - hydroxy - 20b - acetoxy - pregnene, is further oxidized to the 18,11 - lactone of D 4 - 3 - oxo-11b - hydroxy - 20b - acetoxy - pregnene - 18-acid, which on hydrolysis and oxidation gives the 20-ol and then the 20-one, also prepared by oxidation of 21-desoxyaldosterone; in another a by-product of the oxidation of D 5-3-ethylenedioxy - 11b ,18 - oxido - 18 - tetrahydropyranyloxy - 20 - hydroxy - pregnene is D 5 - 3 - ethylenedioxy - 7,20 - dioxo - 11b ,18 - oxido - 18-tetrahydropyranyloxy - pregnene, which with acetic acid yields D 3,5 - 3,18 - dihydroxy 7,20 - dioxo - 11b ,18 - oxido - pregnadiene; and in another D 4-3,20-dioxo-11b ,18-oxido-18-acetoxy-pregnene is prepared by acetylation of the 18-ol. Further examples describe (1) the hydrolysis of D 4 - 3 - oxo - 11b ,18 - oxido - 18-hydroxy - 20b - acetoxy - pregnene to the 20-ol; (2) the reduction of the 18,11-lactone of D 5 - 3 - ethylenedioxy - 11b - hydroxy - 20 - oxo-pregnene - 18 - acid to D 5 - 3 - ethylenedioxy-11b ,18-oxido-18,20a and 20b -dihydroxy-pregnenes, their acetylation to the 18,20a -diacetate; and (3) the conversion of D 4-3,20-dioxo-11b ,18-oxido - 18 - hydroxy - pregnene to the tetrahydropyranyl ether. The 18,20 - lactone of 3,11 - dioxo - 20b - hydroxy - 5b - pregnane - 18 - acid is prepared by oxidation of the corresponding 3a ,11a -dihydroxy-compound. The steroids of the invention, some of which are stated to have an inhibitory effect on the central nervous system, may be made up into pharmaceutical compositions with suitable carriers. These may take the form of tablets, dragees, solutions, suspensions or emulsions and may contain preserving, stabilizing, wetting or emulsifying agents, salts for varying the osmotic pressure or buffers. Specifications 821,779, 946,659 and 973,145 are referred to. |
| priorityDate | 1960-12-16-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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