http://rdf.ncbi.nlm.nih.gov/pubchem/patent/GB-817351-A
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_dc2f7134efa50484bb359fda73782848 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J5-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07J75-00 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J5-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07J75-00 |
| filingDate | 1955-07-15^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 1959-07-29^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | GB-817351-A |
| titleOfInvention | Nor-steroids and preparation thereof |
| abstract | The invention comprises D 12 (or 13)-17b -methyl - 20 - keto - 18 - nor - 17a - compounds of the pregnene series which have at least one hydrogen atom in the 11-position and which have in the 16a -position a free or esterified hydroxyl group or a keto group obtainable from the corresponding 16 : 17a -oxido-20-keto-pregnenes by treatment with an acylating agent in the presence of an acid catalyst, and nitrogen-containing 20-keto-functional derivatives thereof, and D 12-17b -methyl-11,20-diketo-18-nor-17a -pregnenes which have in the 16-position a free or esterified hydroxyl group or a keto group, and nitrogen-containing 20-keto-functional derivatives thereof, and a process for the preparation of 18-nor steroids wherein a 16 : 17-oxido-20-keto-compound of the pregnane series is reacted with an acylating agent in the presence of an acid catalyst, and, if desired, the reaction product is treated with a hydrolysing agent and, if desired, with an oxidizing agent and/or the 20-keto group is converted into a nitrogen-containing fractionally converted keto group and/or any double bonds capable of being hydrogenated are saturated. In the case of the pregnane reactants containing at least one hydrogen atom at the 11-position, the product is probably a 13 : 14 unsaturated compound. Suitable acylating agents are reactive derivatives of aliphatic carboxylic acids such as their anhydrides or halides, strong aliphatic carboxylic acids such as formic acid or halogenacetic acids-particularly trifluoracetic acid. The acylating agent may be used as the solvent or a hydrocarbon such as toluene or a halogenated hydrocarbon may be used as the reaction solvent. Suitable acid catalysts are anhydrous mineral acids, sulphonic acids, and acid salts such as zinc chloride and ferric chloride. The 16 : 17a -oxido-20-keto-pregnane reactants may be substituted in the nucleus or in the side chain, e.g. in the 3-, 5-, 6-, 11-, 12- or 21-position by free or functionally converted hydroxy or keto groups such as acyloxy groups-particularly the formyloxy, trifluoracetoxy, acetoxy-propionyloxy or tosyloxy groups, by alkoxy groups such as methoxy or ethoxy groups, or by acetalised keto groups. The reactants may have any desired configuration and may also contain double bonds, for example, in the 4-, 5-, 9(11)- or 11-position. In the examples: (1) 16 : 17a -oxido-pregnenolone acetate is heated with acetic anhydride and p-toluene sulphonic acid to form D 5:12(or 13) - 3b ,16a - diacetoxy - 17b - methyl-18 - nor - 20 - keto - 17a - pregnadiene which is converted to its semicarbazone or oxime derivative, or is hydrolysed to D 5:12(or 13)-3b ,16a -dihydroxy - 17b - methyl - 18 - nor - 20 - keto - 17a -pregnadiene and further oxidized to D 5-13-3,16,20 - triketo - 17b - methyl - 18 - nor - 17a - pregnadiene; (2) D 5:12(or 13)-3b ,16a - diacetoxy - 17b - methyl - 18 - nor - 20 - keto - 17a - pregnadiene (obtained as in (1)) is hydrogenated to form D 12(or 13)-3b ,16a - diacetoxy - 17b -methyl - 18 - nor - 20 - keto - 17a - allopregnene, is then hydrolysed to the corresponding 3b ,16a -dihydroxy compound and the 3b ,16a -dihydroxy compound oxidized to the corresponding 3 : 16 : 20 - triketo - 17a - allopregnene; (3) 16 : 17a -oxido-pregnenolone acetate is treated with formic acid and concentrated sulphuric acid to form a D 5:12(or 13)-3b - acetoxy - 16a - formyloxy - 17b - methyl - 20 - keto - 17a - pregnadiene which is then hydrolysed as in (1); (4) 16 : 17a -oxido-progesterone is treated with acetic anhydride in the presence of p-toluene sulphonic acid to form D 3:5:12(or 13)-3 : 16a -diacetoxy-20-keto-17b - methyl - 18 - nor - 17a - pregnatriene and is then hydrolysed to a D 4:12(13)-3,20-diketo - 16a - hydroxy - 17b - methyl - 18 - nor-17a - pregnadiene; (5) 3b - acetoxy - 12 : 20-diketo-16:17a -oxido-allopregnane is treated as in (4) to form D 12(or 13)-3b :16a -diacetoxy-12:20 - diketo - 17b - methyl - 18 - nor - 17a - allopregnene which is then hydrolysed to the corresponding 3b :16a -dihydroxy compound; (6) 3a :21 - diacetoxy - 11:20 - diketo - 16:17a -oxido-pregnane is treated as in (4) to form D 12-3a :16a :21 - triacetoxy - 11:20 - diketo - 17b - methyl - 18 - nor - 17a - pregnene which is hydrolysed to the corresponding trihydroxy compound; (7) 3b - acetoxy - 11:20 - diketo - 16:17a - oxido - allopregnane is treated as in (3) to form D 12-3b -acetoxy-11:20-diketo-16a -formyloxy - 17b - methyl - 18 - nor - 17a - allo - pregnene which is then hydrolysed to form D 12-3b :16a - dihydroxy - 11:20 - diketo - 17b -methyl-18-nor-17a -allopregnene. 3b - Acetoxy - 12:20 - diketo - 16:17a - oxido - allopregnane is prepared by treating D 16-3b -acetoxy-12:20-diketo-allopregnene with hydrogen peroxide. 3,17 - Diketo - 18 - nor - D - homo - androstane of the formula <FORM:0817351/IV (b)/1> is prepared by converting the 3b ,16a -diacetoxy compound of Example (1) above into its oxime derivative, carrying out the Beckmann rearrangement on the oxime by treating with p-acetylominobenzene sulphonic acid chloride and hydrolysing the resulting amide to form D 5:12(or 13)-3b ,16a - dihydroxy - 17b - methyl - 17a - amino - androstadiene, treating this compound with periodic acid in aqueous methanol to form a keto-aldehyde of the formula <FORM:0817351/IV (b)/2> treating the keto-aldehyde with potassium tertiary butylate in tertiary butanol to form D 5:13:15:17 - 3b ,17a - dihydroxy - 18 - nor - D - homo - androstatetraene 17a - methyl ether of the formula <FORM:0817351/IV (b)/3> wherein R represents the methyl group, reducing the 17a -methyl ether with lithium and alcohol in liquid ammonia followed by reduction of the crude product with a palladium catalyst to form D 5-3b - oxy - 17a - keto - 18 - nor - D - homo-androstene of the formula <FORM:0817351/IV (b)/4> oxidizing the D 5-18-nor-D-homo-androstene to the corresponding D 4-3-ketone and saturating the 4:5-double bond. |
| priorityDate | 1954-07-16^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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