NL1005808C2 - Hexahydro-aspartaamamiden en werkwijze voor de bereiding ervan. - Google Patents
Hexahydro-aspartaamamiden en werkwijze voor de bereiding ervan. Download PDFInfo
- Publication number
- NL1005808C2 NL1005808C2 NL1005808A NL1005808A NL1005808C2 NL 1005808 C2 NL1005808 C2 NL 1005808C2 NL 1005808 A NL1005808 A NL 1005808A NL 1005808 A NL1005808 A NL 1005808A NL 1005808 C2 NL1005808 C2 NL 1005808C2
- Authority
- NL
- Netherlands
- Prior art keywords
- group
- amide
- hexahydro
- preparation
- aspartame
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 16
- 238000002360 preparation method Methods 0.000 title claims description 10
- 229960003438 aspartame Drugs 0.000 title claims description 6
- 239000000605 aspartame Substances 0.000 title claims description 6
- 150000001408 amides Chemical class 0.000 claims description 16
- 239000003054 catalyst Substances 0.000 claims description 16
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 9
- 238000005984 hydrogenation reaction Methods 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- -1 t-butyloxycarbonyl group Chemical group 0.000 claims description 4
- 150000004702 methyl esters Chemical class 0.000 claims description 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 3
- 230000002785 anti-thrombosis Effects 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000013589 supplement Substances 0.000 claims 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 8
- 235000010357 aspartame Nutrition 0.000 description 8
- 238000007327 hydrogenolysis reaction Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 230000009435 amidation Effects 0.000 description 7
- 238000007112 amidation reaction Methods 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- 229910052697 platinum Inorganic materials 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229910052703 rhodium Inorganic materials 0.000 description 5
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 229960005190 phenylalanine Drugs 0.000 description 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229910052707 ruthenium Inorganic materials 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 1
- 125000006847 BOC protecting group Chemical group 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 125000000570 L-alpha-aspartyl group Chemical group [H]OC(=O)C([H])([H])[C@]([H])(N([H])[H])C(*)=O 0.000 description 1
- 229910003266 NiCo Inorganic materials 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052593 corundum Inorganic materials 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910001845 yogo sapphire Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
- C07K5/06113—Asp- or Asn-amino acid
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL1005808A NL1005808C2 (nl) | 1997-04-14 | 1997-04-14 | Hexahydro-aspartaamamiden en werkwijze voor de bereiding ervan. |
| AU67504/98A AU6750498A (en) | 1997-04-14 | 1998-04-03 | Hexahydroaspartame amides and method for the preparation thereof |
| PCT/NL1998/000189 WO1998046629A1 (fr) | 1997-04-14 | 1998-04-03 | Appareil permettant de mettre graduellement fin a une dependance |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL1005808 | 1997-04-14 | ||
| NL1005808A NL1005808C2 (nl) | 1997-04-14 | 1997-04-14 | Hexahydro-aspartaamamiden en werkwijze voor de bereiding ervan. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL1005808C2 true NL1005808C2 (nl) | 1998-10-19 |
Family
ID=19764786
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL1005808A NL1005808C2 (nl) | 1997-04-14 | 1997-04-14 | Hexahydro-aspartaamamiden en werkwijze voor de bereiding ervan. |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU6750498A (fr) |
| NL (1) | NL1005808C2 (fr) |
| WO (1) | WO1998046629A1 (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2306823A1 (fr) * | 1997-10-10 | 1999-04-22 | Aventis Pharmaceuticals Products Inc. | Preparation des pseudotetrapeptides azacycloalkylalcanoyles |
| DE69900850T2 (de) | 1998-06-05 | 2002-08-29 | Aventis Pharma S.A., Antony Cedex | Verfahren zur herstellung von aspartyl-cyclohexylalaninamid |
| FR2779431B1 (fr) * | 1998-06-05 | 2001-03-09 | Rhone Poulenc Rorer Sa | Procede de preparation de l'aspartyl cyclohexylalaninamide |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0405506A1 (fr) * | 1989-06-30 | 1991-01-02 | Abbott Laboratories | Ligants tétrapeptidiques du type B CCK récepteur |
| WO1991004746A1 (fr) * | 1989-09-29 | 1991-04-18 | Rhone-Poulenc Rorer International (Holdings) Inc. | Peptides et pseudopeptides antithrombotiques |
| US5332726A (en) * | 1989-09-29 | 1994-07-26 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Antithrombotic peptides and pseudopeptides |
-
1997
- 1997-04-14 NL NL1005808A patent/NL1005808C2/nl not_active IP Right Cessation
-
1998
- 1998-04-03 WO PCT/NL1998/000189 patent/WO1998046629A1/fr not_active Ceased
- 1998-04-03 AU AU67504/98A patent/AU6750498A/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0405506A1 (fr) * | 1989-06-30 | 1991-01-02 | Abbott Laboratories | Ligants tétrapeptidiques du type B CCK récepteur |
| WO1991004746A1 (fr) * | 1989-09-29 | 1991-04-18 | Rhone-Poulenc Rorer International (Holdings) Inc. | Peptides et pseudopeptides antithrombotiques |
| US5332726A (en) * | 1989-09-29 | 1994-07-26 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Antithrombotic peptides and pseudopeptides |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998046629A1 (fr) | 1998-10-22 |
| AU6750498A (en) | 1998-11-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0973796B1 (fr) | Procede destine a la preparation et a la purification d'un derive d'aspartame n-alkyle | |
| EP0375040B1 (fr) | Procédé de préparation de peptides retro-inverso et intermédiaires de ceux-ci | |
| US20090247744A1 (en) | Hydroformylation process for pharmaceutical intermediate | |
| FI79329C (fi) | Nytt foerfarande foer framstaellning av pentapeptiden h-arg-x-asp-y-tyr-r och vid foerfarandet anvaenda mellanprodukter. | |
| EP0061933B1 (fr) | Protection de l'histidine | |
| NL1005808C2 (nl) | Hexahydro-aspartaamamiden en werkwijze voor de bereiding ervan. | |
| US4613460A (en) | Process for preparing α-L-aspartyl-L-phenylalanine methyl ester | |
| JPH06509821A (ja) | ペプチドおよびペプチド誘導体の液相合成 | |
| HU208838B (en) | Method for producing peptones containing aza aminoacides by means of solid-phase synthesis | |
| Paris et al. | Post-synthesis modification of aspartyl or glutamyl residue side-chains on solid support | |
| CA2421550C (fr) | Procede de preparation de midodrine, sels pharmaceutiquement acceptables a base de midodrine et intermediaires | |
| JPH08119916A (ja) | Ｎ−保護グルタミン酸γ−誘導体の選択的製造法 | |
| EP0227306A2 (fr) | Peptides immunostimulants | |
| NAITHANI et al. | Synthesis of Protected Decapeptide (B21-30) of Human Insulin | |
| WO2000039071A1 (fr) | Procede de production de l-erythro-(1r, 2s)-2-amino-1-phenylpropan-1-ol | |
| JP2880744B2 (ja) | α―Ｌ―アスパルチル―Ｌ―フェニルアラニンエステルの製造法 | |
| IE49765B1 (en) | Peptides and process for their preparation | |
| WO1992009620A1 (fr) | Procede pour synthetiser en phase de solution un peptide | |
| CN109734627A (zh) | 一种新的化合物n-2-烷酰基-n-6-芴甲氧羰基-l-赖氨酸 | |
| Midura-Nowaczek | Syntheses of methylketones of peptides with C-terminal optically active lysine: Removal of the benzyloxycarbonyl group | |
| JPS5872548A (ja) | ヒスチジン含有ペプチド誘導体の製造法 | |
| JPS63215697A (ja) | 弛緩ペプチドおよびその製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PD2B | A search report has been drawn up | ||
| VD1 | Lapsed due to non-payment of the annual fee |
Effective date: 20011101 |