CA2210519C - Separation des racemates d'amines primaires et secondaires substittuees par des heteroatomes par acylation catalysee par des enzymes - Google Patents
Separation des racemates d'amines primaires et secondaires substittuees par des heteroatomes par acylation catalysee par des enzymes Download PDFInfo
- Publication number
- CA2210519C CA2210519C CA002210519A CA2210519A CA2210519C CA 2210519 C CA2210519 C CA 2210519C CA 002210519 A CA002210519 A CA 002210519A CA 2210519 A CA2210519 A CA 2210519A CA 2210519 C CA2210519 C CA 2210519C
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- substituted amine
- oxygen
- heteroatom
- ester
- 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
- 150000001412 amines Chemical class 0.000 title claims abstract description 84
- 230000010933 acylation Effects 0.000 title claims description 6
- 238000005917 acylation reaction Methods 0.000 title claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 30
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 28
- 239000001301 oxygen Substances 0.000 claims abstract description 27
- 150000002148 esters Chemical class 0.000 claims abstract description 26
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000000203 mixture Substances 0.000 claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 238000006470 amide elimination reaction Methods 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 28
- 230000008569 process Effects 0.000 claims description 28
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 24
- 108090001060 Lipase Proteins 0.000 claims description 15
- 239000004367 Lipase Substances 0.000 claims description 15
- 102000004882 Lipase Human genes 0.000 claims description 15
- 235000019421 lipase Nutrition 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
- JLEKJZUYWFJPMB-UHFFFAOYSA-N ethyl 2-methoxyacetate Chemical group CCOC(=O)COC JLEKJZUYWFJPMB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 150000002926 oxygen Chemical group 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
- 239000002253 acid Substances 0.000 abstract description 7
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 abstract description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052731 fluorine Inorganic materials 0.000 abstract description 4
- 239000011737 fluorine Substances 0.000 abstract description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052698 phosphorus Inorganic materials 0.000 abstract description 3
- 239000011574 phosphorus Substances 0.000 abstract description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 18
- 102000004190 Enzymes Human genes 0.000 description 15
- 108090000790 Enzymes Proteins 0.000 description 15
- 150000001408 amides Chemical class 0.000 description 9
- 102000004157 Hydrolases Human genes 0.000 description 6
- 108090000604 Hydrolases Proteins 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 108010084311 Novozyme 435 Proteins 0.000 description 4
- 241000589516 Pseudomonas Species 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 229940060037 fluorine Drugs 0.000 description 3
- 235000019000 fluorine Nutrition 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 235000014786 phosphorus Nutrition 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- XYXFJNIUUWEUIJ-UHFFFAOYSA-N propan-2-yl 2-methoxyacetate Chemical compound COCC(=O)OC(C)C XYXFJNIUUWEUIJ-UHFFFAOYSA-N 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 108010079522 solysime Proteins 0.000 description 2
- JFFOUICIRBXFRC-RFZPGFLSSA-N (1r,2r)-2-aminocyclopentan-1-ol Chemical compound N[C@@H]1CCC[C@H]1O JFFOUICIRBXFRC-RFZPGFLSSA-N 0.000 description 1
- JIMSXLUBRRQALI-VXGBXAGGSA-N (1r,2r)-2-phenylmethoxycyclopentan-1-amine Chemical compound N[C@@H]1CCC[C@H]1OCC1=CC=CC=C1 JIMSXLUBRRQALI-VXGBXAGGSA-N 0.000 description 1
- MTEZLAATISORQK-UHFFFAOYSA-N 2-methoxyacetamide Chemical class COCC(N)=O MTEZLAATISORQK-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- OPFTUNCRGUEPRZ-QLFBSQMISA-N Cyclohexane Natural products CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 1
- 241001663154 Electron Species 0.000 description 1
- 241001661345 Moesziomyces antarcticus Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000003975 aryl alkyl amines Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229940073584 methylene chloride Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011814 protection agent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000006250 specific catalysis Methods 0.000 description 1
- 230000002311 subsequent effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Un procédé de préparation d'amines primaires et secondaires optiquement actives substituées par des hétéroatomes à partir des racémates correspondants se caractérise par les étapes suivantes: (a) on procède à l'acylation énantiosélective en présence d'une hydrolase d'une amine racémique substituée par un hétéroatome avec un ester dont la composante acide porte un atome de fluor, d'azote, de phosphore, d'oxygène ou de soufre à proximité de l'atome de carbone carbonyle; (b) on sépare le mélange d'amine optiquement active substituée par un hétéroatome et d'amine optiquement active acylée substituée par un hétéroatome de façon à obtenir un énantiomère de l'amine substituée par un hétéroatome; (c) on extrait le cas échéant de l'amine acylée substituée par un hétéroatome l'autre énantiomère de l'amine substituée par un hétéroatome par clivage avec un amide.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19503605 | 1995-02-03 | ||
| DE19523151A DE19523151A1 (de) | 1995-02-03 | 1995-06-29 | Racematspaltung primärer und sekundärer heteroatomsubstituierter Amine durch Enzym-katalysierte Acylierung |
| DE19503605.0 | 1995-06-29 | ||
| DE19523151.1 | 1995-06-29 | ||
| PCT/EP1996/000234 WO1996023894A1 (fr) | 1995-02-03 | 1996-01-20 | Separation des racemates d'amines primaires et secondaires substituees par des heteroatomes par acylation catalysee par des enzymes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2210519A1 CA2210519A1 (fr) | 1996-08-08 |
| CA2210519C true CA2210519C (fr) | 2006-03-21 |
Family
ID=36101519
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002210519A Expired - Lifetime CA2210519C (fr) | 1995-02-03 | 1996-01-20 | Separation des racemates d'amines primaires et secondaires substittuees par des heteroatomes par acylation catalysee par des enzymes |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2210519C (fr) |
-
1996
- 1996-01-20 CA CA002210519A patent/CA2210519C/fr not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA2210519A1 (fr) | 1996-08-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20160120 |