SE440506B - Forfarande for framstellning av alfa-l-aspartyl-l-fenylalaninmetylester - Google Patents
Forfarande for framstellning av alfa-l-aspartyl-l-fenylalaninmetylesterInfo
- Publication number
- SE440506B SE440506B SE7714709A SE7714709A SE440506B SE 440506 B SE440506 B SE 440506B SE 7714709 A SE7714709 A SE 7714709A SE 7714709 A SE7714709 A SE 7714709A SE 440506 B SE440506 B SE 440506B
- Authority
- SE
- Sweden
- Prior art keywords
- aspartyl
- phenylalanine
- reaction medium
- moles
- apm
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
- 239000012429 reaction media Substances 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 239000007787 solid Substances 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 12
- YZQCXOFQZKCETR-UWVGGRQHSA-N Asp-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 YZQCXOFQZKCETR-UWVGGRQHSA-N 0.000 claims description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
- WYYUBJAMROQJSF-QWRGUYRKSA-N (3s)-4-[[(1s)-1-carboxy-2-phenylethyl]amino]-3-formamido-4-oxobutanoic acid Chemical group OC(=O)C[C@H](NC=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 WYYUBJAMROQJSF-QWRGUYRKSA-N 0.000 claims description 4
- 230000008030 elimination Effects 0.000 claims description 4
- 238000003379 elimination reaction Methods 0.000 claims description 4
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 3
- 229960005190 phenylalanine Drugs 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims 2
- 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 claims 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 229910000039 hydrogen halide Inorganic materials 0.000 description 9
- 239000012433 hydrogen halide Substances 0.000 description 9
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
- 235000019253 formic acid Nutrition 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- 238000005886 esterification reaction Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- -1 carbobenzoxy, t-butoxycarbonyl Chemical group 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- WJGAPUXHSQQWQF-UHFFFAOYSA-N acetic acid;hydrochloride Chemical compound Cl.CC(O)=O WJGAPUXHSQQWQF-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000007257 deesterification reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- DFTMVZIUYVECNW-VKHMYHEASA-N n-[(3s)-2,5-dioxooxolan-3-yl]formamide Chemical compound O=CN[C@H]1CC(=O)OC1=O DFTMVZIUYVECNW-VKHMYHEASA-N 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- 238000010490 three component reaction Methods 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
- C07K5/06121—Asp- or Asn-amino acid the second amino acid being aromatic or cycloaliphatic
- C07K5/0613—Aspartame
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)
- Seasonings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75429776A | 1976-12-27 | 1976-12-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE7714709L SE7714709L (sv) | 1978-06-28 |
| SE440506B true SE440506B (sv) | 1985-08-05 |
Family
ID=25034194
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE7714709A SE440506B (sv) | 1976-12-27 | 1977-12-23 | Forfarande for framstellning av alfa-l-aspartyl-l-fenylalaninmetylester |
Country Status (18)
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59219258A (ja) * | 1983-05-28 | 1984-12-10 | Ajinomoto Co Inc | α−Ｌ−アスパルチル−Ｌ−フエニルアラニンメチルエステル又はその塩酸塩の製法 |
| JPS59225152A (ja) * | 1983-06-02 | 1984-12-18 | Ajinomoto Co Inc | α−Ｌ−アスパルチル−Ｌ−フエニルアラニンメチルエステル又はその塩酸塩の製法 |
| US4618695A (en) * | 1983-06-02 | 1986-10-21 | Ajinomoto Co., Inc. | Method of preparing methyl ester and its hydrochloride |
| GB8321802D0 (en) * | 1983-08-12 | 1983-09-14 | Erba Farmitalia | Aspartame synthesis |
| JPH07636B2 (ja) * | 1984-12-17 | 1995-01-11 | 三井東圧化学株式会社 | Ｎ−ホルミル−α−アスパルチルフエニルアラニンの製造法 |
| CA1277098C (en) * | 1984-12-27 | 1990-11-27 | Mitsui Toatsu Chemicals, Inc. | Preparation process of -l-aspartyl-l-phenylalanine methyl ester |
| AU561384B2 (en) * | 1985-03-26 | 1987-05-07 | Mitsui Toatsu Chemicals Inc. | Preparation of -l-aspartyl-l-phenylalanine methyl ester or hydrochloride thereof |
| AU586669B2 (en) * | 1985-03-29 | 1989-07-20 | Mitsui Toatsu Chemicals Inc. | Preparation process of ```-L-aspartyl-L-phenylalanine methyl ester or hydrochloride thereof |
| DE3600731A1 (de) * | 1986-01-13 | 1987-07-16 | Green Cross Korea | Verfahren zur herstellung von (alpha)-l-aspartyl-l-phenylalaninmethylester |
| JPS6383098A (ja) * | 1986-09-27 | 1988-04-13 | Ajinomoto Co Inc | α−Ｌ−アスパルチル−Ｌ−フエニルアラニン又はその誘導体の製造方法 |
| ES2042583T3 (es) * | 1986-12-05 | 1993-12-16 | Mitsui Toatsu Chemicals | Preparacion de metil ester de alpha-l-aspartil-l-fenil-alanina o uno de sus hidrohaluros. |
| JPH0832719B2 (ja) * | 1986-12-19 | 1996-03-29 | 三井東圧化学株式会社 | 吸湿性の小さいα−Ｌ−アスパルチル−Ｌ−フエニルアラニンメチルエステルの製造法 |
| JPS6411999U (enrdf_load_stackoverflow) * | 1987-07-13 | 1989-01-23 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5232371B2 (enrdf_load_stackoverflow) * | 1972-07-20 | 1977-08-20 | ||
| US3933781A (en) * | 1973-11-05 | 1976-01-20 | Monsanto Company | Process for the preparation of α-L-aspartyl-L-phenylalanine alkyl esters |
| JPS5223001A (en) * | 1975-08-14 | 1977-02-21 | Ajinomoto Co Inc | Process for elimination of formyl group |
-
1977
- 1977-12-16 MX MX776726U patent/MX4704E/es unknown
- 1977-12-22 ZA ZA00777614A patent/ZA777614B/xx unknown
- 1977-12-23 NL NLAANVRAGE7714351,A patent/NL185211C/xx not_active IP Right Cessation
- 1977-12-23 BE BE183786A patent/BE862258A/xx not_active IP Right Cessation
- 1977-12-23 SE SE7714709A patent/SE440506B/sv not_active IP Right Cessation
- 1977-12-23 AU AU32014/77A patent/AU515038B2/en not_active Expired
- 1977-12-23 IT IT31246/77A patent/IT1088938B/it active
- 1977-12-23 DK DK577977A patent/DK149432C/da not_active IP Right Cessation
- 1977-12-23 NO NO774440A patent/NO148069C/no unknown
- 1977-12-23 DE DE19772757771 patent/DE2757771A1/de active Granted
- 1977-12-23 GB GB53633/77A patent/GB1546979A/en not_active Expired
- 1977-12-23 CA CA293,911A patent/CA1100487A/en not_active Expired
- 1977-12-24 HU HU77MO1000A patent/HU179735B/hu unknown
- 1977-12-26 FR FR7739203A patent/FR2375194A1/fr active Granted
- 1977-12-26 JP JP52155755A patent/JPS6050200B2/ja not_active Expired
- 1977-12-26 BR BR7708632A patent/BR7708632A/pt unknown
- 1977-12-26 SU SU772557552A patent/SU884564A3/ru active
- 1977-12-27 CH CH1592977A patent/CH631435A5/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| AU515038B2 (en) | 1981-03-12 |
| CH631435A5 (en) | 1982-08-13 |
| AU3201477A (en) | 1979-06-28 |
| SE7714709L (sv) | 1978-06-28 |
| GB1546979A (en) | 1979-06-06 |
| MX4704E (es) | 1982-08-04 |
| FR2375194B1 (enrdf_load_stackoverflow) | 1984-04-13 |
| NO148069B (no) | 1983-04-25 |
| IT1088938B (it) | 1985-06-10 |
| JPS5382752A (en) | 1978-07-21 |
| CA1100487A (en) | 1981-05-05 |
| HU179735B (en) | 1982-12-28 |
| DK149432C (da) | 1987-04-21 |
| DK577977A (da) | 1978-06-28 |
| DE2757771A1 (de) | 1978-07-06 |
| NL7714351A (nl) | 1978-06-29 |
| ZA777614B (en) | 1978-10-25 |
| NO774440L (no) | 1978-06-28 |
| JPS6050200B2 (ja) | 1985-11-07 |
| DK149432B (da) | 1986-06-09 |
| BR7708632A (pt) | 1978-08-22 |
| FR2375194A1 (fr) | 1978-07-21 |
| DE2757771C2 (enrdf_load_stackoverflow) | 1988-08-25 |
| NO148069C (no) | 1983-08-03 |
| BE862258A (fr) | 1978-06-23 |
| NL185211B (nl) | 1989-09-18 |
| NL185211C (nl) | 1990-02-16 |
| SU884564A3 (ru) | 1981-11-23 |
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