CA1299813C - METHOD OF SEPARATING .alpha.-L-ASPARTYL-L-PHENYLALANINE METHYL ESTER THROUGH CRYSTALLIZATION - Google Patents
METHOD OF SEPARATING .alpha.-L-ASPARTYL-L-PHENYLALANINE METHYL ESTER THROUGH CRYSTALLIZATIONInfo
- Publication number
- CA1299813C CA1299813C CA000456100A CA456100A CA1299813C CA 1299813 C CA1299813 C CA 1299813C CA 000456100 A CA000456100 A CA 000456100A CA 456100 A CA456100 A CA 456100A CA 1299813 C CA1299813 C CA 1299813C
- Authority
- CA
- Canada
- Prior art keywords
- water
- alcohol
- solution
- mixture
- aspartyl
- 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 - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 46
- YZQCXOFQZKCETR-UHFFFAOYSA-N aspartyl-phenylalanine Chemical compound OC(=O)CC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 YZQCXOFQZKCETR-UHFFFAOYSA-N 0.000 title claims abstract 6
- 238000002425 crystallisation Methods 0.000 title claims description 11
- 230000008025 crystallization Effects 0.000 title claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 51
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 150000002148 esters Chemical class 0.000 claims abstract description 10
- 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 description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- 239000000203 mixture Substances 0.000 claims description 22
- 239000013078 crystal Substances 0.000 claims description 15
- 238000001816 cooling Methods 0.000 claims description 13
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 239000002826 coolant Substances 0.000 claims description 5
- 238000001704 evaporation Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims 1
- 235000003599 food sweetener Nutrition 0.000 abstract description 3
- 239000003765 sweetening agent Substances 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 27
- 239000012046 mixed solvent Substances 0.000 description 15
- 239000012535 impurity Substances 0.000 description 12
- 238000004090 dissolution Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229960005261 aspartic acid Drugs 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000002301 combined effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000003507 refrigerant Substances 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 238000009834 vaporization Methods 0.000 description 2
- 230000008016 vaporization Effects 0.000 description 2
- GWKOSRIHVSBBIA-REOHCLBHSA-N (3s)-3-aminooxolane-2,5-dione Chemical compound N[C@H]1CC(=O)OC1=O GWKOSRIHVSBBIA-REOHCLBHSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical class CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 230000000063 preceeding effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000005979 thermal decomposition 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
-
- 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58102327A JPS59227849A (ja) | 1983-06-08 | 1983-06-08 | Ｌ―α―アスパルチル―Ｌ―フェニルアラニンメチルエステル束状晶の晶析分離法 |
| JP102327/1983 | 1983-06-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1299813C true CA1299813C (en) | 1992-04-28 |
Family
ID=14324442
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000456100A Expired - Lifetime CA1299813C (en) | 1983-06-08 | 1984-06-07 | METHOD OF SEPARATING .alpha.-L-ASPARTYL-L-PHENYLALANINE METHYL ESTER THROUGH CRYSTALLIZATION |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US4994605A (en, 2012) |
| EP (1) | EP0128694A3 (en, 2012) |
| JP (1) | JPS59227849A (en, 2012) |
| KR (1) | KR920000648B1 (en, 2012) |
| CA (1) | CA1299813C (en, 2012) |
| IE (1) | IE58987B1 (en, 2012) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60174799A (ja) * | 1984-02-21 | 1985-09-09 | 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の製造法 |
| AU586669B2 (en) * | 1985-03-29 | 1989-07-20 | Mitsui Toatsu Chemicals Inc. | Preparation process of ```-L-aspartyl-L-phenylalanine methyl ester or hydrochloride thereof |
| 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 |
| AU600176B2 (en) * | 1987-10-13 | 1990-08-02 | Mitsui Toatsu Chemicals Inc. | Preparation method of alpha-l-aspartyl-l-phenylalanine methyl ester having improved solubilization |
| CA2017137A1 (en) * | 1989-05-22 | 1990-11-22 | Shigeaki Irino | Method for crystallizing &-l-aspartyl-l-phenylalanine methyl ester |
| JPH0327398A (ja) * | 1989-06-26 | 1991-02-05 | Mitsui Toatsu Chem Inc | α―Ｌ―アスパルチル―Ｌ―フェニルアラニンメチルエステルの晶析方法 |
| US5591886A (en) * | 1990-11-05 | 1997-01-07 | Mitsui Toatsu Chemicals, Incorporated | Process for the crystallizing L-α-aspartyl-L-phenylalanine methyl ester from the solution |
| EP0510552B2 (en) * | 1991-04-24 | 2000-11-15 | MITSUI TOATSU CHEMICALS, Inc. | Preparation process of alpha-aspartyl-L-phenylalanine methyl ester |
| JP2946853B2 (ja) * | 1991-05-09 | 1999-09-06 | 味の素株式会社 | アスパルテームの晶析法 |
| JP2927070B2 (ja) * | 1991-05-23 | 1999-07-28 | 味の素株式会社 | α−Ｌ−アスパルチル−Ｌ−フェニルアラニンメチルエステルの製造方法 |
| JP2979761B2 (ja) * | 1991-05-23 | 1999-11-15 | 味の素株式会社 | α−Ｌ−アスパルチル−Ｌ−フェニルアラニンメチルエステル塩酸塩の製造法 |
| US5391810A (en) * | 1991-05-23 | 1995-02-21 | Ajinomoto Co., Inc. | Method of crystallizing α-L-aspartyl-L-phenylalanine methyl ester |
| US5473097A (en) * | 1991-05-24 | 1995-12-05 | Ajinomoto Company, Inc. | Granules of α-L-aspartyl-L-phenylalanine methyl ester |
| JPH05178889A (ja) * | 1991-10-30 | 1993-07-20 | Ajinomoto Co Inc | α−Ｌ−アスパルチル−Ｌ−フェニルアラニンメチルエステルの晶析方法 |
| JPH05286994A (ja) * | 1992-04-13 | 1993-11-02 | Tosoh Corp | α−Ｌ−アスパルチル−Ｌ−フェニルアラニンメチルエステルの晶析法 |
| JP3239452B2 (ja) * | 1992-08-05 | 2001-12-17 | 味の素株式会社 | α−Ｌ−アスパルチル−Ｌ−フェニルアラニンメチルエステル塩酸塩の製造法 |
| US5728862A (en) * | 1997-01-29 | 1998-03-17 | The Nutrasweet Company | Method for preparing and purifying an N-alkylated aspartame derivative |
| US6657073B1 (en) | 1999-08-18 | 2003-12-02 | Daesang Corporation | Crystallization of α-L-aspartyl-L-phenylalanine methyl ester |
| KR100464559B1 (ko) * | 2002-03-22 | 2005-01-03 | 정남교 | 벨크로 테이프 제조장치 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1309605A (en) * | 1970-01-31 | 1973-03-14 | Ajinomoto Kk | Process for producing alpha-dipeptide esters of l-aspartic acid |
| CA1027112A (en) * | 1973-03-05 | 1978-02-28 | Willard M. Hoehn | Process for isolation of dipeptide esters |
| US4017472A (en) * | 1973-03-05 | 1977-04-12 | G. D. Searle & Co. | Process for isolation of aspartyl dipeptide esters |
| US3901871A (en) * | 1973-09-21 | 1975-08-26 | American Cyanamid Co | Process of preparing ' -l-aspartyl-l-phenylalanine methyl ester |
| US4394308A (en) * | 1980-05-27 | 1983-07-19 | Chimicasa Gmbh | Method of producing α-L-aspartyl-L-phenylalanine methylesters |
-
1983
- 1983-06-08 JP JP58102327A patent/JPS59227849A/ja active Granted
-
1984
- 1984-05-28 IE IE132684A patent/IE58987B1/en not_active IP Right Cessation
- 1984-05-29 EP EP84303589A patent/EP0128694A3/en not_active Ceased
- 1984-06-04 KR KR1019840003108A patent/KR920000648B1/ko not_active Expired
- 1984-06-07 CA CA000456100A patent/CA1299813C/en not_active Expired - Lifetime
-
1989
- 1989-04-25 US US07/342,894 patent/US4994605A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| IE58987B1 (en) | 1993-12-15 |
| KR920000648B1 (ko) | 1992-01-20 |
| US4994605A (en) | 1991-02-19 |
| JPH0377199B2 (en, 2012) | 1991-12-09 |
| JPS59227849A (ja) | 1984-12-21 |
| EP0128694A3 (en) | 1986-11-26 |
| IE841326L (en) | 1984-12-08 |
| EP0128694A2 (en) | 1984-12-19 |
| KR850000465A (ko) | 1985-02-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |