JP2008231046A - 光学活性カルニチンアミドハロゲン化物の精製方法 - Google Patents
光学活性カルニチンアミドハロゲン化物の精製方法 Download PDFInfo
- Publication number
- JP2008231046A JP2008231046A JP2007074531A JP2007074531A JP2008231046A JP 2008231046 A JP2008231046 A JP 2008231046A JP 2007074531 A JP2007074531 A JP 2007074531A JP 2007074531 A JP2007074531 A JP 2007074531A JP 2008231046 A JP2008231046 A JP 2008231046A
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- carnitine amide
- amide halide
- halide
- carnitine
- 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.)
- Pending
Links
- -1 carnitine amide halide Chemical class 0.000 title claims abstract description 71
- 238000000034 method Methods 0.000 title claims abstract description 26
- 230000003287 optical effect Effects 0.000 claims abstract description 51
- 238000002425 crystallisation Methods 0.000 claims abstract description 29
- 230000008025 crystallization Effects 0.000 claims abstract description 29
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 claims abstract description 23
- 150000004820 halides Chemical class 0.000 claims description 14
- 239000013078 crystal Substances 0.000 claims description 12
- 239000013543 active substance Substances 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- PHIQHXFUZVPYII-LURJTMIESA-N (S)-carnitine Chemical compound C[N+](C)(C)C[C@@H](O)CC([O-])=O PHIQHXFUZVPYII-LURJTMIESA-N 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 239000002243 precursor Substances 0.000 abstract description 4
- 230000004129 fatty acid metabolism Effects 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 150000001875 compounds Chemical class 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- JXXCENBLGFBQJM-FYZOBXCZSA-N [(2r)-3-carboxy-2-hydroxypropyl]-trimethylazanium;chloride Chemical compound [Cl-].C[N+](C)(C)C[C@H](O)CC(O)=O JXXCENBLGFBQJM-FYZOBXCZSA-N 0.000 description 3
- 229960004203 carnitine Drugs 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 0 C[*+](C)C[C@@](CC(N)=O)O Chemical compound C[*+](C)C[C@@](CC(N)=O)O 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003849 aromatic solvent Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- KWIXGIMKELMNGH-UHFFFAOYSA-O carnitinamide Chemical compound C[N+](C)(C)CC(O)CC(N)=O KWIXGIMKELMNGH-UHFFFAOYSA-O 0.000 description 2
- PHIQHXFUZVPYII-UHFFFAOYSA-N carnitine Chemical compound C[N+](C)(C)CC(O)CC([O-])=O PHIQHXFUZVPYII-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003759 ester based solvent Substances 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000005453 ketone based solvent Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 208000037997 venous disease Diseases 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- LSPHULWDVZXLIL-LDWIPMOCSA-N (?)-Camphoric acid Chemical compound CC1(C)[C@@H](C(O)=O)CC[C@@]1(C)C(O)=O LSPHULWDVZXLIL-LDWIPMOCSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000001258 dyslipidemic effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- LYMHIBZGTAPASQ-UHFFFAOYSA-N ethcathinone Chemical compound CCNC(C)C(=O)C1=CC=CC=C1 LYMHIBZGTAPASQ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000013048 microbiological method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000011085 pressure filtration Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007074531A JP2008231046A (ja) | 2007-03-22 | 2007-03-22 | 光学活性カルニチンアミドハロゲン化物の精製方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007074531A JP2008231046A (ja) | 2007-03-22 | 2007-03-22 | 光学活性カルニチンアミドハロゲン化物の精製方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008231046A true JP2008231046A (ja) | 2008-10-02 |
| JP2008231046A5 JP2008231046A5 (enExample) | 2010-04-22 |
Family
ID=39904281
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007074531A Pending JP2008231046A (ja) | 2007-03-22 | 2007-03-22 | 光学活性カルニチンアミドハロゲン化物の精製方法 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2008231046A (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015221807A (ja) * | 2009-11-18 | 2015-12-10 | ロンザ リミテッドＬｏｎｚａ Ｌｉｍｉｔｅｄ | Ｌ−カルニチンの製造方法 |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5513299A (en) * | 1978-07-10 | 1980-01-30 | Cavazza Claudio | Manufacture of camphoric acid carnitine amide |
| JPS6191160A (ja) * | 1984-10-09 | 1986-05-09 | Nisshin Flour Milling Co Ltd | Ｌ−カルニチンの製造法 |
| JPH01287065A (ja) * | 1988-05-13 | 1989-11-17 | Kanegafuchi Chem Ind Co Ltd | カルニチンの製造方法 |
| JPH02243636A (ja) * | 1988-12-14 | 1990-09-27 | Nutrasweet Co | ラセミ体混合物からｌ―異性体の単離方法 |
| JPH05117170A (ja) * | 1991-04-12 | 1993-05-14 | Degussa Ag | Ｌ−カルニチンの製造法 |
| JPH08119921A (ja) * | 1994-10-24 | 1996-05-14 | Ajinomoto Co Inc | ＤＬ−α−アミノ酸−Ｎ−（Ｓ）−α−アルキルベンジルアミドのジアステレオマ−分割法 |
| JPH10101628A (ja) * | 1996-09-27 | 1998-04-21 | Tosoh Corp | アミノ酸及びその誘導体の高光学純度の光学活性体の製造法 |
| WO2006028068A1 (ja) * | 2004-09-08 | 2006-03-16 | Wako Pure Chemical Industries, Ltd. | Ｌ－カルニチンの精製方法 |
-
2007
- 2007-03-22 JP JP2007074531A patent/JP2008231046A/ja active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5513299A (en) * | 1978-07-10 | 1980-01-30 | Cavazza Claudio | Manufacture of camphoric acid carnitine amide |
| JPS6191160A (ja) * | 1984-10-09 | 1986-05-09 | Nisshin Flour Milling Co Ltd | Ｌ−カルニチンの製造法 |
| JPH01287065A (ja) * | 1988-05-13 | 1989-11-17 | Kanegafuchi Chem Ind Co Ltd | カルニチンの製造方法 |
| JPH02243636A (ja) * | 1988-12-14 | 1990-09-27 | Nutrasweet Co | ラセミ体混合物からｌ―異性体の単離方法 |
| JPH05117170A (ja) * | 1991-04-12 | 1993-05-14 | Degussa Ag | Ｌ−カルニチンの製造法 |
| JPH08119921A (ja) * | 1994-10-24 | 1996-05-14 | Ajinomoto Co Inc | ＤＬ−α−アミノ酸−Ｎ−（Ｓ）−α−アルキルベンジルアミドのジアステレオマ−分割法 |
| JPH10101628A (ja) * | 1996-09-27 | 1998-04-21 | Tosoh Corp | アミノ酸及びその誘導体の高光学純度の光学活性体の製造法 |
| WO2006028068A1 (ja) * | 2004-09-08 | 2006-03-16 | Wako Pure Chemical Industries, Ltd. | Ｌ－カルニチンの精製方法 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015221807A (ja) * | 2009-11-18 | 2015-12-10 | ロンザ リミテッドＬｏｎｚａ Ｌｉｍｉｔｅｄ | Ｌ−カルニチンの製造方法 |
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