NO143346B - PROCEDURE FOR THE PREPARATION OF THYMOSIN ALFA / 1 - Google Patents
PROCEDURE FOR THE PREPARATION OF THYMOSIN ALFA / 1 Download PDFInfo
- Publication number
- NO143346B NO143346B NO773681A NO773681A NO143346B NO 143346 B NO143346 B NO 143346B NO 773681 A NO773681 A NO 773681A NO 773681 A NO773681 A NO 773681A NO 143346 B NO143346 B NO 143346B
- Authority
- NO
- Norway
- Prior art keywords
- preparation
- acetate
- methyl
- dione
- procedure
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title claims abstract description 4
- 102000007501 Thymosin Human genes 0.000 title abstract 2
- 108010046075 Thymosin Proteins 0.000 title abstract 2
- LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 title abstract 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 5
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- 230000003444 anaesthetic effect Effects 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- 239000013067 intermediate product Substances 0.000 claims 1
- 239000000047 product Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 239000000126 substance Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- -1 steroid compound Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/57581—Thymosin; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Fremgangsmåte ved fremstilling av thymosin a.Process for the preparation of thymosin a.
Description
Fremgangsmåte til fremstilling av 16a-metyl-pregnan-3a- Process for the production of 16a-methyl-pregnan-3a-
Foreliggende oppfinnelse angår en fremgangsmåte til fremstilling av en ny steroidforbindelse, nemlig 16a-metyl-preg-nan-3ct-ol-ll,20-3-acetat under anvendelse av 16-pregnen-3a-ol-ll,20-dioner-3-acetat som utgangsmateriale. The present invention relates to a method for the production of a new steroid compound, namely 16a-methyl-pregnan-3ct-ol-11,20-3-acetate using 16-pregnen-3a-ol-11,20-diones-3 -acetate as starting material.
Denne nye forbindelse har sterk anestetisk virkning og er videre fordelaktig som mellomprodukt ved fremstilling av 16a-me-tyl-l,4-pregnadien-17a-ol-3,20-dion og med denne beslektede forbindelser. Sistnevnte forbindelser har en ytterst sterk anti-in-f lammatorisk virkning. This new compound has a strong anesthetic effect and is furthermore advantageous as an intermediate in the preparation of 16a-methyl-1,4-pregnadien-17a-ol-3,20-dione and related compounds. The latter compounds have an extremely strong anti-inflammatory effect.
Den forbindelse som fåes ved frem-gangsmåten ifølge foreliggende oppfinnelse, har strukturformelen: The compound obtained by the method according to the present invention has the structural formula:
Det karakteristiske trekk ved frem-gangsmåten ifølge oppfinnelsen er at man omsetter 16-pregnen-3a-ol-ll,20-dion-3-acetat med metylmagnesiumjodid i nær-være av kuproklorid, hydrolyserer produk-tet og forestrer med eddiksyreanhydrid. The characteristic feature of the process according to the invention is that 16-pregnen-3a-ol-11,20-dione-3-acetate is reacted with methylmagnesium iodide in the presence of cuprous chloride, the product is hydrolysed and esterified with acetic anhydride.
I det følgende beskrives som eksempel en utførelsesform for oppfinnelsen. In the following, an embodiment of the invention is described as an example.
Eksempel. Example.
En oppløsning av 10,22 g metyljodid i 50 ml eter tilsettes til 1,73 g magnesium i 50 ml eter. Den oppløsning av metylmagnesiumjodid i eter man herved får, tilsettes i nitrogenatmosfære 0,045 g vannfritt kuproklorid. Den herved erholdte blanding tilsettes i løpet av omkring 1 time, mens reaksjonsblandingen omrøres kraftig og hol-des på omkring romtemperatur, en oppløs-ning av omkring 5,6 g 16-pregnen-3a-ol-11,20-3-acetat i 175 ml eter. Under denne tilsetning utskilles et kornet, fast stoff. Den resulterende blanding oppvarmes under svak kokning med tilbakeløpskjøling i 2 timer, hvorpå reaksjonsblandingen avkjø-les, og tilsettes 125 ml mettet, vandig am-moniumkloridoppløsning med derpå følgen-de tilsetning av 200 ml eter. Skiktene skil-les fra hverandre, og eterskiktet vaskes med tre porsjoner vann hver på 50 ml. Det vas-kede eterskikt tørres, og oppløsningsmidlet fordampes i vakuum, hvorved man får et brunt, viskost, oljeaktig stoff. Dette stoff oppvarmes i 15 minutter ved 60—70°C med en blanding av 25 ml eddiksyreanhydrid og 25 ml pyridin. Det således acetylerte produkt renses ved kromatografi i syrevasket aluminiumoxyd med påfølgende omkrystal-lisasjon fra petroleter, hvorved man får omkring 1,5 g i det vesentlige rent 16a-metyl-pregnen-3a-ol-ll,20-dion-3-acetat. A solution of 10.22 g of methyl iodide in 50 ml of ether is added to 1.73 g of magnesium in 50 ml of ether. The solution of methylmagnesium iodide in ether thus obtained is added in a nitrogen atmosphere to 0.045 g of anhydrous cupric chloride. A solution of about 5.6 g of 16-pregnen-3a-ol-11,20-3-acetate in 175 ml of ether. During this addition, a granular, solid substance separates. The resulting mixture is heated under gentle boiling with reflux for 2 hours, after which the reaction mixture is cooled, and 125 ml of saturated, aqueous ammonium chloride solution is added, followed by the addition of 200 ml of ether. The layers are separated, and the ether layer is washed with three portions of water each of 50 ml. The washed ether layer is dried, and the solvent is evaporated in a vacuum, whereby a brown, viscous, oily substance is obtained. This substance is heated for 15 minutes at 60-70°C with a mixture of 25 ml of acetic anhydride and 25 ml of pyridine. The thus acetylated product is purified by chromatography in acid-washed aluminum oxide with subsequent recrystallization from petroleum ether, whereby approximately 1.5 g of essentially pure 16a-methyl-pregnen-3a-ol-11,20-dione-3-acetate is obtained.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73663876A | 1976-10-28 | 1976-10-28 | |
| US05/766,638 US4079127A (en) | 1976-10-28 | 1977-02-08 | Thymosin alpha 1 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO773681L NO773681L (en) | 1978-05-02 |
| NO143346B true NO143346B (en) | 1980-10-13 |
| NO143346C NO143346C (en) | 1981-01-21 |
Family
ID=27113070
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO773681A NO143346C (en) | 1976-10-28 | 1977-10-27 | PROCEDURE FOR THE PREPARATION OF THYMOSIN ALFA1 |
Country Status (22)
| Country | Link |
|---|---|
| JP (1) | JPS5411220A (en) |
| AR (1) | AR214903A1 (en) |
| AT (1) | AT362493B (en) |
| AU (1) | AU514996B2 (en) |
| CA (1) | CA1101842A (en) |
| CH (1) | CH633258A5 (en) |
| DE (1) | DE2748213A1 (en) |
| DK (1) | DK149094C (en) |
| ES (1) | ES463588A1 (en) |
| FI (1) | FI56317C (en) |
| FR (1) | FR2369248A1 (en) |
| GB (1) | GB1590457A (en) |
| IL (1) | IL53218A (en) |
| IT (1) | IT1195254B (en) |
| LU (1) | LU78395A1 (en) |
| MC (1) | MC1167A1 (en) |
| NL (1) | NL188699C (en) |
| NO (1) | NO143346C (en) |
| NZ (1) | NZ185519A (en) |
| PT (1) | PT67204B (en) |
| SE (1) | SE442479B (en) |
| YU (1) | YU40314B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2919592A1 (en) * | 1979-05-15 | 1981-01-15 | Max Planck Gesellschaft | METHOD FOR PRODUCING THYMOSINE ALPHA 1 AND DERIVATIVES THEREOF |
| US4339427A (en) * | 1980-04-14 | 1982-07-13 | Hoffmann-La Roche Inc. | Radioimmunoassay of thymosinα |
| FR2492663B1 (en) * | 1980-10-24 | 1985-11-08 | Vtoroi Mo G | MEDICINAL PRODUCT REGULATING THE IMMUNITY T-SYSTEM AND ITS PREPARATION METHOD |
| DE3137231A1 (en) * | 1981-09-18 | 1983-04-14 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen | BIS-THYMOSINE (ALPHA) (DOWN ARROW) 1 (DOWN ARROW) CONNECTIONS |
| JPH01250018A (en) * | 1988-03-30 | 1989-10-05 | Noble Sangyo Kk | Displacement detector electronic measuring instrument |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1195980A (en) * | 1966-08-24 | 1970-06-24 | Univ Yeshiva | Hormone-Like Preparations Derived from Thymus Gland and Methods of Producing the Same. |
-
1977
- 1977-10-05 CH CH1216177A patent/CH633258A5/en not_active IP Right Cessation
- 1977-10-14 AU AU29699/77A patent/AU514996B2/en not_active Expired
- 1977-10-25 IL IL53218A patent/IL53218A/en unknown
- 1977-10-26 SE SE7712071A patent/SE442479B/en not_active IP Right Cessation
- 1977-10-26 CA CA289,510A patent/CA1101842A/en not_active Expired
- 1977-10-26 MC MC771268A patent/MC1167A1/en unknown
- 1977-10-26 NZ NZ185519A patent/NZ185519A/en unknown
- 1977-10-26 IT IT29020/77A patent/IT1195254B/en active
- 1977-10-26 JP JP12766677A patent/JPS5411220A/en active Granted
- 1977-10-26 FR FR7732259A patent/FR2369248A1/en active Granted
- 1977-10-27 DE DE19772748213 patent/DE2748213A1/en active Granted
- 1977-10-27 LU LU7778395A patent/LU78395A1/xx unknown
- 1977-10-27 AT AT765877A patent/AT362493B/en not_active IP Right Cessation
- 1977-10-27 PT PT67204A patent/PT67204B/en unknown
- 1977-10-27 YU YU2578/77A patent/YU40314B/en unknown
- 1977-10-27 NL NLAANVRAGE7711814,A patent/NL188699C/en not_active IP Right Cessation
- 1977-10-27 DK DK478277A patent/DK149094C/en not_active IP Right Cessation
- 1977-10-27 NO NO773681A patent/NO143346C/en unknown
- 1977-10-27 AR AR269752A patent/AR214903A1/en active
- 1977-10-27 ES ES463588A patent/ES463588A1/en not_active Expired
- 1977-10-28 FI FI773221A patent/FI56317C/en not_active IP Right Cessation
- 1977-10-28 GB GB45001/77A patent/GB1590457A/en not_active Expired
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