CA2339639C - Synthese d'oligosaccharides programmable monotope - Google Patents
Synthese d'oligosaccharides programmable monotope Download PDFInfo
- Publication number
- CA2339639C CA2339639C CA2339639A CA2339639A CA2339639C CA 2339639 C CA2339639 C CA 2339639C CA 2339639 A CA2339639 A CA 2339639A CA 2339639 A CA2339639 A CA 2339639A CA 2339639 C CA2339639 C CA 2339639C
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- Prior art keywords
- glycosyl
- donor
- acceptors
- protected
- donors
- Prior art date
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- 150000002482 oligosaccharides Chemical class 0.000 title claims abstract description 61
- 229920001542 oligosaccharide Polymers 0.000 title claims abstract description 57
- 238000005580 one pot reaction Methods 0.000 title claims abstract description 33
- 238000003786 synthesis reaction Methods 0.000 title claims description 44
- 230000015572 biosynthetic process Effects 0.000 title claims description 40
- 230000009257 reactivity Effects 0.000 claims abstract description 118
- 239000000386 donor Substances 0.000 claims abstract description 67
- 125000003147 glycosyl group Chemical group 0.000 claims abstract description 64
- 239000000348 glycosyl donor Substances 0.000 claims abstract description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims description 51
- 239000000370 acceptor Substances 0.000 claims description 43
- 239000000937 glycosyl acceptor Substances 0.000 claims description 35
- 230000008569 process Effects 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 238000009833 condensation Methods 0.000 claims description 5
- 230000005494 condensation Effects 0.000 claims description 5
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- 238000006482 condensation reaction Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000006872 improvement Effects 0.000 claims description 2
- 230000002250 progressing effect Effects 0.000 claims description 2
- 238000003860 storage Methods 0.000 claims description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 abstract description 53
- 229930182475 S-glycoside Natural products 0.000 abstract description 27
- 125000006239 protecting group Chemical group 0.000 abstract description 24
- 150000003569 thioglycosides Chemical class 0.000 abstract description 23
- -1 p-methylphenyl thioglycoside Chemical class 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 18
- 238000013459 approach Methods 0.000 abstract description 11
- 238000004128 high performance liquid chromatography Methods 0.000 abstract description 10
- 229930182470 glycoside Natural products 0.000 abstract description 9
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- 150000002338 glycosides Chemical class 0.000 abstract description 7
- 238000004590 computer program Methods 0.000 abstract description 6
- 238000011161 development Methods 0.000 abstract description 4
- 125000001483 monosaccharide substituent group Chemical group 0.000 abstract 1
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- 101150041968 CDC13 gene Proteins 0.000 description 81
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 70
- 239000000203 mixture Substances 0.000 description 59
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 44
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 39
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- 238000006243 chemical reaction Methods 0.000 description 36
- 239000000047 product Substances 0.000 description 34
- 239000000243 solution Substances 0.000 description 33
- 238000006206 glycosylation reaction Methods 0.000 description 32
- 230000013595 glycosylation Effects 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
- 150000001875 compounds Chemical class 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- 239000007832 Na2SO4 Substances 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
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- 235000011152 sodium sulphate Nutrition 0.000 description 21
- UDCDOJQOXWCCSD-UHFFFAOYSA-N N,N-dimethyl-N'-p-tolylsulfamide Chemical compound CN(C)S(=O)(=O)NC1=CC=C(C)C=C1 UDCDOJQOXWCCSD-UHFFFAOYSA-N 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 20
- 238000004587 chromatography analysis Methods 0.000 description 18
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 18
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- 239000000741 silica gel Substances 0.000 description 17
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 17
- 229910001868 water Inorganic materials 0.000 description 17
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 16
- 239000012267 brine Substances 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- 235000000346 sugar Nutrition 0.000 description 15
- 239000011734 sodium Substances 0.000 description 14
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 13
- 239000000543 intermediate Substances 0.000 description 13
- 239000006188 syrup Substances 0.000 description 13
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- 238000004440 column chromatography Methods 0.000 description 12
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
- 238000005859 coupling reaction Methods 0.000 description 11
- 229930182830 galactose Natural products 0.000 description 11
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 230000008878 coupling Effects 0.000 description 10
- 238000010168 coupling process Methods 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
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- 239000002904 solvent Substances 0.000 description 10
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 9
- 229960002317 succinimide Drugs 0.000 description 9
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 230000009849 deactivation Effects 0.000 description 8
- 150000002016 disaccharides Chemical class 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 150000008195 galaktosides Chemical class 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 150000008146 mannosides Chemical class 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 150000004044 tetrasaccharides Chemical class 0.000 description 7
- 150000004043 trisaccharides Chemical class 0.000 description 7
- 238000010626 work up procedure Methods 0.000 description 7
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 239000006227 byproduct Substances 0.000 description 6
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- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000002808 molecular sieve Substances 0.000 description 6
- 239000000178 monomer Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 5
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- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 5
- 150000001720 carbohydrates Chemical class 0.000 description 5
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- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 4
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 4
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- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
- C07H3/06—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16C—COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
- G16C20/00—Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
- G16C20/10—Analysis or design of chemical reactions, syntheses or processes
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16C—COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
- G16C20/00—Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
- G16C20/90—Programming languages; Computing architectures; Database systems; Data warehousing
-
- 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)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Theoretical Computer Science (AREA)
- Computing Systems (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Health & Medical Sciences (AREA)
- Crystallography & Structural Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Bioinformatics & Computational Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Databases & Information Systems (AREA)
- Software Systems (AREA)
- Saccharide Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
La réactivité d'un certain nombre de p-méthylphénylthioglycosides (STol) donneurs, qui sont soit entièrement protégés soit présentent un groupe hydroxyle exposé, a été déterminée quantitativement par chromatographie liquide haute performance (CLHP), conjointement au développement d'une approche à application large de synthèse monotope facile d'oligosaccharides. L'influence des effets structurels de différents noyaux monosaccharidiques et de différents groupes protecteurs sur chaque glycoside donneur sur cette réactivité a été caractérisée et quantifiée. De plus, on a établi une corrélation entre la réactivité des donneurs de glycosyle et le déplacement chimique du proton anomère par RMN de 1H.Une base de données de thioglycosides en tant que donneurs de glycosyle a été créée à l'aide de ces données de réactivité. Son utilité a été démontrée par l'assemblage monotope facile et rapide de diverses structures oligosaccharidiques linéaires ou ramifiées. De plus, on décrit un programme informatique servant d'outil pour la consultation de bases de données et de guide pour la sélection des entités servant à l'assemblage monotope d'un oligosaccharide recherché ou d'une bibliothèque d'oligosaccharides individuels.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9600198P | 1998-08-10 | 1998-08-10 | |
| US60/096,001 | 1998-08-10 | ||
| PCT/US1999/018151 WO2000009527A1 (fr) | 1998-08-10 | 1999-08-10 | Synthese d'oligosaccharides programmable monotope |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2339639A1 CA2339639A1 (fr) | 2000-02-24 |
| CA2339639C true CA2339639C (fr) | 2010-09-28 |
Family
ID=22254590
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2339639A Expired - Fee Related CA2339639C (fr) | 1998-08-10 | 1999-08-10 | Synthese d'oligosaccharides programmable monotope |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1104433A4 (fr) |
| JP (1) | JP2002522598A (fr) |
| AU (1) | AU773115B2 (fr) |
| CA (1) | CA2339639C (fr) |
| WO (1) | WO2000009527A1 (fr) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009155108A1 (fr) * | 2008-05-30 | 2009-12-23 | Momenta Pharmaceuticals, Inc. | Structures saccharides et procédés destinés à fabriquer et à utiliser de telles structures |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5463564A (en) * | 1994-09-16 | 1995-10-31 | 3-Dimensional Pharmaceuticals, Inc. | System and method of automatically generating chemical compounds with desired properties |
| GB9517661D0 (en) * | 1995-08-30 | 1995-11-01 | Smithkline Beecham Plc | Novel compounds |
-
1999
- 1999-08-10 CA CA2339639A patent/CA2339639C/fr not_active Expired - Fee Related
- 1999-08-10 JP JP2000564977A patent/JP2002522598A/ja active Pending
- 1999-08-10 EP EP99943670A patent/EP1104433A4/fr not_active Withdrawn
- 1999-08-10 WO PCT/US1999/018151 patent/WO2000009527A1/fr not_active Ceased
- 1999-08-10 AU AU56720/99A patent/AU773115B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002522598A (ja) | 2002-07-23 |
| AU773115B2 (en) | 2004-05-20 |
| AU5672099A (en) | 2000-03-06 |
| EP1104433A4 (fr) | 2005-06-15 |
| CA2339639A1 (fr) | 2000-02-24 |
| WO2000009527A1 (fr) | 2000-02-24 |
| EP1104433A1 (fr) | 2001-06-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20150810 |