GB815692A - Improvements in or relating to 12a-aza-c-homopregnane-12,20-dione derivatives - Google Patents
Improvements in or relating to 12a-aza-c-homopregnane-12,20-dione derivativesInfo
- Publication number
- GB815692A GB815692A GB21884/57A GB2188457A GB815692A GB 815692 A GB815692 A GB 815692A GB 21884/57 A GB21884/57 A GB 21884/57A GB 2188457 A GB2188457 A GB 2188457A GB 815692 A GB815692 A GB 815692A
- Authority
- GB
- United Kingdom
- Prior art keywords
- aza
- homo
- hydroxy
- dione
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 abstract 9
- 150000001875 compounds Chemical class 0.000 abstract 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 abstract 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract 4
- 239000004593 Epoxy Substances 0.000 abstract 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 abstract 4
- 230000003301 hydrolyzing effect Effects 0.000 abstract 4
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 abstract 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 abstract 3
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 abstract 3
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 abstract 3
- 230000001590 oxidative effect Effects 0.000 abstract 3
- 150000002923 oximes Chemical class 0.000 abstract 3
- 239000000047 product Substances 0.000 abstract 3
- 239000001632 sodium acetate Substances 0.000 abstract 3
- 235000017281 sodium acetate Nutrition 0.000 abstract 3
- 239000004289 sodium hydrogen sulphite Substances 0.000 abstract 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 abstract 3
- VUXXCVWHUXQPFJ-UHFFFAOYSA-N 1-methylsulfanyl-4-methylsulfinyl-6,7-dihydro-5h-cyclopenta[d]pyridazine Chemical compound CSC1=NN=C(S(C)=O)C2=C1CCC2 VUXXCVWHUXQPFJ-UHFFFAOYSA-N 0.000 abstract 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 abstract 2
- 238000006237 Beckmann rearrangement reaction Methods 0.000 abstract 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 abstract 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 abstract 2
- 229960000583 acetic acid Drugs 0.000 abstract 2
- 239000012467 final product Substances 0.000 abstract 2
- 239000012362 glacial acetic acid Substances 0.000 abstract 2
- 239000001257 hydrogen Substances 0.000 abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract 2
- 238000005984 hydrogenation reaction Methods 0.000 abstract 2
- -1 hydroxymethylene Chemical group 0.000 abstract 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 abstract 2
- 235000011118 potassium hydroxide Nutrition 0.000 abstract 2
- 150000003128 pregnanes Chemical class 0.000 abstract 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 abstract 1
- XUWDLCJMVNFEDO-FHLCJRBUSA-N [(1R,2S,4S,6R,7S,8R,9S,12S,13S,16S,18S)-10-hydroxyimino-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,2'-oxane]-16-yl] acetate Chemical compound C(C)(=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4C[C@H]5[C@H]([C@H](C)[C@]6(O5)CCC(C)CO6)[C@]4(C(C[C@@H]3[C@]2(CC1)C)=NO)C XUWDLCJMVNFEDO-FHLCJRBUSA-N 0.000 abstract 1
- 230000000397 acetylating effect Effects 0.000 abstract 1
- 125000002252 acyl group Chemical group 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 abstract 1
- 239000003638 chemical reducing agent Substances 0.000 abstract 1
- 229910052801 chlorine Inorganic materials 0.000 abstract 1
- 229940117975 chromium trioxide Drugs 0.000 abstract 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- 150000002440 hydroxy compounds Chemical class 0.000 abstract 1
- 150000002978 peroxides Chemical class 0.000 abstract 1
- 235000011056 potassium acetate Nutrition 0.000 abstract 1
- 238000010992 reflux Methods 0.000 abstract 1
- INLFWQCRAJUDCR-LYLBMTSKSA-N spirostane Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CCCCC4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 INLFWQCRAJUDCR-LYLBMTSKSA-N 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention comprises 12a-aza-C-homo-5a -pregnanes of the general formula <FORM:0815692/IV (b)/1> and the 16-dehydro, 16,17-epoxy and 17-hydroxy derivatives thereof, wherein X represents an hydroxymethylene or carbonyl radical or an alkanoyloxymethylene radical in which the alkanoyl portion is of the formula <FORM:0815692/IV (b)/2> lower alkyl, the alkyl radical being of the CnH2n+1 type wherein n is less than 7. The pregnanes and the 16-dehydro derivatives thereof may be prepared by forming the oxime of hecogenin acetate, subjecting the oxime to the Beckmann rearrangement to form 3b -acetoxy-12a-aza-C-homo - 5a - spirostan - 12 - one, reacting the spirostan with acetic anhydride, chromic oxide and sodium acetate successively to form 3b -acetoxy - 12a - aza - C - homo - 5a - pregn - 16 - ene-12,20-dione (optionally hydrolysing this compound to form the corresponding 3-hydroxy compound and, if necessary, esterifying the 3-hydroxy group to form 16-dehydro-compounds of the above general formula in which X is an hydroxymethylene or an alkanoyloxymethylene radical), hydrogenating the 3b -acetoxy-12a-aza - C - homo - 5a - pregn - 16 - ene - 12,20-dione to form the corresponding pregnanes (optionally hydrolysing this compound to form 12a - aza - 3b - hydroxy - C - homo - 5a - pregnane - 12,20 - dione and, if necessary, esterifying the 3-hydroxy group as above), and oxidizing the 12a-aza-3b -hydroxy-C-homo-5a -pregnane-12,20-dione by treatment with t-butyl hypochlorite, the resulting 12a-aza-C-homo-N-chloro-5a -pregnane-3,12,20-trione being treated with sodium bisulphite or a similar reducing agent to replace the N-chlorine atom by an N-hydrogen atom to form 12a-aza-C-homo-5a -pregnane-3,12,20-trione. The 16,17-epoxy-3-alcohol derivative is prepared by treating the 16-dehydro-3-acetate of the above general formula with alkaline peroxide, and, if necessary, esterifying or oxidizing as above through the N-chloro-compound to form the desired 3-ester or 3-ketone respectively thereof. The 3,17-diol of the above general formula is prepared by treating the 16-17-epoxy-3-alcohol with hydrobromic acid and hydrogen, the hydrogenation being carried out in the presence of a hydrogenation catalyst such as palladium on calcium carbonate. The 3,17-diols may be converted to the corresponding 3-oxo compound by treating with t-butyl hypochlorite as above through the N-chloro-compound. In the examples: (1) 3b -acetoxy - 12a - aza - C - homo - 5a - pregn - 16-ene-12,20-dione is prepared by treating hecogenin acetate with hydroxylamine hydrochloride to form 3b -acetoxy-5a -spirostan-12-one oxime, then applying the Beckmann rearrangement to the oxime to form 3b -acetoxy-12a-aza-C-homo-5a -spirostan-12-one, and finally treating this compound successively with acetic anhydride, chromic trioxide and sodium acetate; (2) 12a-aza - 3b - hydroxy - C - homo - 5a - pregn - 16-ene-12,20-dione is prepared by hydrolysing the final product of (1) with caustic potash; (3) 3b - acetoxy - 12a - aza - C - homo - 5a - pregnone-12,20-dione is prepared by hydrogenating the product of (1) in the presence of pre-reduced palladium on charcoal, and then hydrolysing to the corresponding free 3-hydroxy compound as in (2); (4) 12a-aza-C-homo-5a -pregnone-3,12,20-trione is prepared by treating the free hydroxy compound of (3) with t-butyl hypochlorite in t-butyl alcohol and then sodium bisulphite; (5) 12a - aza - 16a ,17a - epoxy - 3b -hydroxy - C - homo - 5a - pregnane - 12,20-dione is prepared by treating the final product of (1) with hydrogen peroxide in the presence of aqueous caustic potash; (6) 12a-aza-16a ,17a -epoxy - C - homo - 5a - pregnane - 3,12,20-trione is prepared by treating the product of (5) with t-butyl hypochlorite in the presence of t-butyl alcohol to form 12a-aza-N-chloro-16a , 17a - epoxy - C - homo - 5a - pregnane - 3,12,20-trione and treating this compound with potassium acetate, glacial acetic acid and sodium bisulphite; (7) 12a - aza - 3b - acetoxy - 17a - hydroxy - C - homo - 5a - pregnane - 12,20 - dione is prepared by treating the product of (5) with hydrobromic acid in the presence of glacial acetic acid to form 3b - acetoxy - 12a - 16b -bromo - 17a - hydroxy - C - homo - 5a - pregnane-12,20-dione, treating this compound with hydrogen in the presence of alcohol and palladium on calcium carbonate to form 12a-aza-3b ,17a -dihydroxy - C - homo - 5a - pregnane - 12,20-dione and acetylating this compound at the 3-position; (3) 12a - aza - 17a - hydroxy - C-homo - 5a - pregnane - 3,12,20 - trione is prepared by oxidizing the corresponding 3-hydroxy compound as in (4); (9) 12a-aza-C-homo-5a - pregn - 16 - ene - 3,12,20 - trione is prepared by refluxing 12a-aza-C-homo-5a -spirostane - 3,12 - dione with acetic anhydride and pyridine hydrochloride to form 12a-aza-26-hydroxy - 5a - furost - 20(22) - ene - 3,12 - dione of the formula <FORM:0815692/IV (b)/3> and treating this compound successively with chromium trioxide and sodium acetate.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US815692XA | 1956-07-16 | 1956-07-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB815692A true GB815692A (en) | 1959-07-01 |
Family
ID=22164985
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB21884/57A Expired GB815692A (en) | 1956-07-16 | 1957-07-10 | Improvements in or relating to 12a-aza-c-homopregnane-12,20-dione derivatives |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB815692A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3143543A (en) * | 1964-08-04 | Certificate of correction |
-
1957
- 1957-07-10 GB GB21884/57A patent/GB815692A/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3143543A (en) * | 1964-08-04 | Certificate of correction |
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