DE2162164C2 - Verfahren zur Herstellung von N hoch delta (Al), N hoch epsilon(B29)-Bis-tert.-butyl-oxycarbonyl-insulin - Google Patents
Verfahren zur Herstellung von N hoch delta (Al), N hoch epsilon(B29)-Bis-tert.-butyl-oxycarbonyl-insulinInfo
- Publication number
- DE2162164C2 DE2162164C2 DE19712162164 DE2162164A DE2162164C2 DE 2162164 C2 DE2162164 C2 DE 2162164C2 DE 19712162164 DE19712162164 DE 19712162164 DE 2162164 A DE2162164 A DE 2162164A DE 2162164 C2 DE2162164 C2 DE 2162164C2
- Authority
- DE
- Germany
- Prior art keywords
- insulin
- boc
- reaction
- tert
- azide
- 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
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Substances N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims description 63
- 229940125396 insulin Drugs 0.000 title claims description 37
- 238000000034 method Methods 0.000 title claims 6
- 238000004519 manufacturing process Methods 0.000 title claims 3
- 102000004877 Insulin Human genes 0.000 claims description 28
- 108090001061 Insulin Proteins 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- ISHLCKAQWKBMAU-UHFFFAOYSA-N tert-butyl n-diazocarbamate Chemical compound CC(C)(C)OC(=O)N=[N+]=[N-] ISHLCKAQWKBMAU-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 2
- 150000001408 amides Chemical class 0.000 claims 2
- 125000003277 amino group Chemical group 0.000 claims 2
- 239000012043 crude product Substances 0.000 claims 2
- 230000007423 decrease Effects 0.000 claims 2
- 238000004925 denaturation Methods 0.000 claims 2
- 230000036425 denaturation Effects 0.000 claims 2
- 239000004026 insulin derivative Substances 0.000 claims 2
- 150000007530 organic bases Chemical class 0.000 claims 2
- 239000011877 solvent mixture Substances 0.000 claims 2
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 claims 1
- 241000251468 Actinopterygii Species 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- 241000283153 Cetacea Species 0.000 claims 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 241000406668 Loxodonta cyclotis Species 0.000 claims 1
- 241000283973 Oryctolagus cuniculus Species 0.000 claims 1
- 241000700159 Rattus Species 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- 150000001298 alcohols Chemical class 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 239000000010 aprotic solvent Substances 0.000 claims 1
- 239000012062 aqueous buffer Substances 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- HGNKNSVAQIVPMU-UHFFFAOYSA-N azido n-diazocarbamate Chemical compound [N-]=[N+]=NOC(=O)N=[N+]=[N-] HGNKNSVAQIVPMU-UHFFFAOYSA-N 0.000 claims 1
- 235000015278 beef Nutrition 0.000 claims 1
- 239000006227 byproduct Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 230000002349 favourable effect Effects 0.000 claims 1
- 230000001771 impaired effect Effects 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 235000015277 pork Nutrition 0.000 claims 1
- 239000000047 product Substances 0.000 claims 1
- 230000035484 reaction time Effects 0.000 claims 1
- 230000000717 retained effect Effects 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 241000894007 species Species 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 claims 1
- -1 tetramethyl sulfon Chemical compound 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010626 work up procedure Methods 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
- C07K14/62—Insulins
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BE792817D BE792817A (fr) | 1971-12-15 | Procede de preparation de n exp. alpha(a1) n exp. epsilon(b29) -bis-tert.-butyl-oxycarbonyl-insuline | |
| DE19712162164 DE2162164C2 (de) | 1971-12-15 | 1971-12-15 | Verfahren zur Herstellung von N hoch delta (Al), N hoch epsilon(B29)-Bis-tert.-butyl-oxycarbonyl-insulin |
| NL7216708A NL7216708A (OSRAM) | 1971-12-15 | 1972-12-08 | |
| CA158,803A CA988080A (en) | 1971-12-15 | 1972-12-08 | PROCESS FOR PREPARING N.alpha.(A1), N? N.epsilon.(B29)-BIS-TERT.-BUTYLOZY-CARBONYL INSULIN |
| CH1805372A CH574910A5 (OSRAM) | 1971-12-15 | 1972-12-12 | |
| JP12470772A JPS4867289A (OSRAM) | 1971-12-15 | 1972-12-12 | |
| FR7244555A FR2163617B1 (OSRAM) | 1971-12-15 | 1972-12-14 | |
| AT1065072A AT330376B (de) | 1971-12-15 | 1972-12-14 | Verfahren zur herstellung von n alfa (a1), n epsilon(b29)-bis-tert.-butyloxycarbonylinsulin |
| GB5801772A GB1402037A (en) | 1971-12-15 | 1972-12-15 | Process for preparing nalpha-a1,nepsilon-b2-9-bis-tert.- butyloxycarbonyl insulin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19712162164 DE2162164C2 (de) | 1971-12-15 | 1971-12-15 | Verfahren zur Herstellung von N hoch delta (Al), N hoch epsilon(B29)-Bis-tert.-butyl-oxycarbonyl-insulin |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2162164A1 DE2162164A1 (OSRAM) | 1973-03-15 |
| DE2162164B1 DE2162164B1 (de) | 1973-03-15 |
| DE2162164C2 true DE2162164C2 (de) | 1973-10-18 |
Family
ID=5828028
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19712162164 Expired DE2162164C2 (de) | 1971-12-15 | 1971-12-15 | Verfahren zur Herstellung von N hoch delta (Al), N hoch epsilon(B29)-Bis-tert.-butyl-oxycarbonyl-insulin |
Country Status (9)
| Country | Link |
|---|---|
| JP (1) | JPS4867289A (OSRAM) |
| AT (1) | AT330376B (OSRAM) |
| BE (1) | BE792817A (OSRAM) |
| CA (1) | CA988080A (OSRAM) |
| CH (1) | CH574910A5 (OSRAM) |
| DE (1) | DE2162164C2 (OSRAM) |
| FR (1) | FR2163617B1 (OSRAM) |
| GB (1) | GB1402037A (OSRAM) |
| NL (1) | NL7216708A (OSRAM) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL7110277A (OSRAM) * | 1970-07-31 | 1972-02-02 |
-
0
- BE BE792817D patent/BE792817A/xx unknown
-
1971
- 1971-12-15 DE DE19712162164 patent/DE2162164C2/de not_active Expired
-
1972
- 1972-12-08 CA CA158,803A patent/CA988080A/en not_active Expired
- 1972-12-08 NL NL7216708A patent/NL7216708A/xx unknown
- 1972-12-12 JP JP12470772A patent/JPS4867289A/ja active Pending
- 1972-12-12 CH CH1805372A patent/CH574910A5/xx not_active IP Right Cessation
- 1972-12-14 AT AT1065072A patent/AT330376B/de active
- 1972-12-14 FR FR7244555A patent/FR2163617B1/fr not_active Expired
- 1972-12-15 GB GB5801772A patent/GB1402037A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| AT330376B (de) | 1976-06-25 |
| JPS4867289A (OSRAM) | 1973-09-13 |
| DE2162164A1 (OSRAM) | 1973-03-15 |
| FR2163617A1 (OSRAM) | 1973-07-27 |
| CA988080A (en) | 1976-04-27 |
| CH574910A5 (OSRAM) | 1976-04-30 |
| FR2163617B1 (OSRAM) | 1976-10-29 |
| NL7216708A (OSRAM) | 1973-06-19 |
| GB1402037A (en) | 1975-08-06 |
| BE792817A (fr) | 1973-06-15 |
| ATA1065072A (de) | 1975-09-15 |
| DE2162164B1 (de) | 1973-03-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| E77 | Valid patent as to the heymanns-index 1977 | ||
| EHJ | Ceased/non-payment of the annual fee |