NO143346B - Fremgangsmaate ved fremstilling av thymosin alfa/1 - Google Patents
Fremgangsmaate ved fremstilling av 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.
Description
Fremgangsmåte til fremstilling av 16a-metyl-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.
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.
Den forbindelse som fåes ved frem-gangsmåten ifølge foreliggende oppfinnelse, har strukturformelen:
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.
I det følgende beskrives som eksempel en utførelsesform for oppfinnelsen.
Eksempel.
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.
Claims (1)
- Fremgangsmåte til fremstilling av 16a-metyl-pregnan-3a-ol-ll,20-dion-3-acetatmed anestetisk virkning og som kan anven-; des som mellomprodukt ved fremstilling av 16a-metyl-l,4-pregnadien-17a-ol-3,20-dion- forbindelser, karakterisert ved at man omsetter 16-pregnen-3a-ol-ll,20-dion-3-acetat med metylmagnesiumjodid i nærvær av kuproklorid, hydrolyserer det dannede produkt og forestrer med eddiksyreanhydrid.
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 (no) | 1978-05-02 |
| NO143346B true NO143346B (no) | 1980-10-13 |
| NO143346C NO143346C (no) | 1981-01-21 |
Family
ID=27113070
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO773681A NO143346C (no) | 1976-10-28 | 1977-10-27 | Fremgangsmaate ved fremstilling av thymosin alfa1 |
Country Status (22)
| Country | Link |
|---|---|
| JP (1) | JPS5411220A (no) |
| AR (1) | AR214903A1 (no) |
| AT (1) | AT362493B (no) |
| AU (1) | AU514996B2 (no) |
| CA (1) | CA1101842A (no) |
| CH (1) | CH633258A5 (no) |
| DE (1) | DE2748213A1 (no) |
| DK (1) | DK149094C (no) |
| ES (1) | ES463588A1 (no) |
| FI (1) | FI56317C (no) |
| FR (1) | FR2369248A1 (no) |
| GB (1) | GB1590457A (no) |
| IL (1) | IL53218A (no) |
| IT (1) | IT1195254B (no) |
| LU (1) | LU78395A1 (no) |
| MC (1) | MC1167A1 (no) |
| NL (1) | NL188699C (no) |
| NO (1) | NO143346C (no) |
| NZ (1) | NZ185519A (no) |
| PT (1) | PT67204B (no) |
| SE (1) | SE442479B (no) |
| YU (1) | YU40314B (no) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2919592A1 (de) * | 1979-05-15 | 1981-01-15 | Max Planck Gesellschaft | Verfahren zur herstellung von thymosin- alpha 1 und derivaten davon |
| US4339427A (en) * | 1980-04-14 | 1982-07-13 | Hoffmann-La Roche Inc. | Radioimmunoassay of thymosinα |
| FR2492663B1 (fr) * | 1980-10-24 | 1985-11-08 | Vtoroi Mo G | Produit medicamenteux regulateur du t-systeme de l'immunite et son procede de preparation |
| DE3137231A1 (de) * | 1981-09-18 | 1983-04-14 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen | Bis-thymosin(alpha)(pfeil abwaerts)1(pfeil abwaerts)-verbindungen |
| JPH01250018A (ja) * | 1988-03-30 | 1989-10-05 | Noble Sangyo Kk | 電子計測器用変位検知器 |
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/de not_active IP Right Cessation
- 1977-10-14 AU AU29699/77A patent/AU514996B2/en not_active Expired
- 1977-10-25 IL IL53218A patent/IL53218A/xx unknown
- 1977-10-26 NZ NZ185519A patent/NZ185519A/xx unknown
- 1977-10-26 MC MC771268A patent/MC1167A1/xx unknown
- 1977-10-26 CA CA289,510A patent/CA1101842A/en not_active Expired
- 1977-10-26 FR FR7732259A patent/FR2369248A1/fr active Granted
- 1977-10-26 JP JP12766677A patent/JPS5411220A/ja active Granted
- 1977-10-26 SE SE7712071A patent/SE442479B/xx not_active IP Right Cessation
- 1977-10-26 IT IT29020/77A patent/IT1195254B/it active
- 1977-10-27 AR AR269752A patent/AR214903A1/es active
- 1977-10-27 DE DE19772748213 patent/DE2748213A1/de active Granted
- 1977-10-27 LU LU7778395A patent/LU78395A1/xx unknown
- 1977-10-27 ES ES463588A patent/ES463588A1/es not_active Expired
- 1977-10-27 NL NLAANVRAGE7711814,A patent/NL188699C/xx not_active IP Right Cessation
- 1977-10-27 AT AT765877A patent/AT362493B/de not_active IP Right Cessation
- 1977-10-27 DK DK478277A patent/DK149094C/da not_active IP Right Cessation
- 1977-10-27 YU YU2578/77A patent/YU40314B/xx unknown
- 1977-10-27 PT PT67204A patent/PT67204B/pt unknown
- 1977-10-27 NO NO773681A patent/NO143346C/no unknown
- 1977-10-28 GB GB45001/77A patent/GB1590457A/en not_active Expired
- 1977-10-28 FI FI773221A patent/FI56317C/fi not_active IP Right Cessation
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