CA2362570A1 - Synthese stereoselective d'analogues nucleosidiques - Google Patents
Synthese stereoselective d'analogues nucleosidiques Download PDFInfo
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- CA2362570A1 CA2362570A1 CA002362570A CA2362570A CA2362570A1 CA 2362570 A1 CA2362570 A1 CA 2362570A1 CA 002362570 A CA002362570 A CA 002362570A CA 2362570 A CA2362570 A CA 2362570A CA 2362570 A1 CA2362570 A1 CA 2362570A1
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- 230000000707 stereoselective effect Effects 0.000 title description 5
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- 125000003118 aryl group Chemical group 0.000 claims abstract description 11
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 5
- 108091005804 Peptidases Proteins 0.000 claims description 81
- 229940088598 enzyme Drugs 0.000 claims description 54
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- OQCFWECOQNPQCG-UHFFFAOYSA-N 1,3,4,8-tetrahydropyrimido[4,5-c]oxazin-7-one Chemical compound C1CONC2=C1C=NC(=O)N2 OQCFWECOQNPQCG-UHFFFAOYSA-N 0.000 description 1
- BCAWWPAPHSAUQZ-RNFRBKRXSA-N 1-[(2r,4r)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)OC1 BCAWWPAPHSAUQZ-RNFRBKRXSA-N 0.000 description 1
- WHSAZJZPFFJHKA-UHFFFAOYSA-N 2,2-dimethoxyethyl benzoate Chemical compound COC(OC)COC(=O)C1=CC=CC=C1 WHSAZJZPFFJHKA-UHFFFAOYSA-N 0.000 description 1
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- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 101000715666 Bos taurus Bile salt-activated lipase Proteins 0.000 description 1
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- 108090000317 Chymotrypsin Proteins 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
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- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- RBNPOMFGQQGHHO-REOHCLBHSA-N L-glyceric acid Chemical compound OC[C@H](O)C(O)=O RBNPOMFGQQGHHO-REOHCLBHSA-N 0.000 description 1
- IJCKBIINTQEGLY-UHFFFAOYSA-N N(4)-acetylcytosine Chemical compound CC(=O)NC1=CC=NC(=O)N1 IJCKBIINTQEGLY-UHFFFAOYSA-N 0.000 description 1
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- ATSMZGDYBPOXMZ-BRFYHDHCSA-N [(2r)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]-1,3-dioxolan-2-yl]methanol Chemical compound C=12N=CN(C3O[C@H](CO)OC3)C2=NC(N)=NC=1NC1CC1 ATSMZGDYBPOXMZ-BRFYHDHCSA-N 0.000 description 1
- SXHGYAAPHCFGCV-MLWJPKLSSA-N [(2s)-4-(2-aminopurin-9-yl)-1,3-dioxolan-2-yl]methanol Chemical compound C12=NC(N)=NC=C2N=CN1C1CO[C@H](CO)O1 SXHGYAAPHCFGCV-MLWJPKLSSA-N 0.000 description 1
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
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- 238000010533 azeotropic distillation Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
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- AIHCVGFMFDEUMO-UHFFFAOYSA-N diiodosilane Chemical group I[SiH2]I AIHCVGFMFDEUMO-UHFFFAOYSA-N 0.000 description 1
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- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 150000002972 pentoses Chemical class 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- JFLRBGOBOJWPHI-UHFFFAOYSA-N pyridin-1-ium-1-sulfonate Chemical compound [O-]S(=O)(=O)[N+]1=CC=CC=C1 JFLRBGOBOJWPHI-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 238000010512 small scale reaction Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
- C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
- C12P41/005—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of carboxylic acid groups in the enantiomers or the inverse reaction
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention concerne un procédé de fabrication d'analogues nucléosidiques de dioxolane purs au plan stéréochimique. Ledit procédé consiste à utiliser l'enzyme hydrolytique pour la séparation des anomères .beta. et .alpha. d'un mélange anomère représenté par la formule A ou la formule B, dans lesquelles W représente benzyle ou benzoyle ; R¿1? est choisi dans le groupe constitué d'alkyle C¿1-6? et d'aryle C¿6-15?.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11975699P | 1999-02-11 | 1999-02-11 | |
| US60/119,756 | 1999-02-11 | ||
| US11988599P | 1999-02-12 | 1999-02-12 | |
| US60/119,885 | 1999-02-12 | ||
| PCT/CA2000/000144 WO2000047759A1 (fr) | 1999-02-11 | 2000-02-11 | Synthese stereoselective d'analogues nucleosidiques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2362570A1 true CA2362570A1 (fr) | 2000-08-17 |
Family
ID=26817660
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002362570A Abandoned CA2362570A1 (fr) | 1999-02-11 | 2000-02-11 | Synthese stereoselective d'analogues nucleosidiques |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1151133A1 (fr) |
| JP (1) | JP2002538780A (fr) |
| AU (1) | AU2653200A (fr) |
| CA (1) | CA2362570A1 (fr) |
| WO (1) | WO2000047759A1 (fr) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2385349A1 (fr) | 1999-09-24 | 2001-04-05 | Francis J. Giles | Methode de traitement ou de prevention d'infections virales au moyen d'analogues nucleosidiques |
| US6566365B1 (en) | 1999-11-04 | 2003-05-20 | Biochem Pharma Inc. | Method for the treatment of Flaviviridea viral infection using nucleoside analogues |
| ATE360016T1 (de) | 2000-02-11 | 2007-05-15 | Shire Biochem Inc | Ein stereoselektives verfahren zur herstellung von nukleosidanalogen |
| WO2002051852A1 (fr) * | 2000-12-27 | 2002-07-04 | Mitsui Chemicals, Inc. | Procede de production d'un derive de saccharide non naturel |
| US7955835B2 (en) | 2002-11-18 | 2011-06-07 | Shire Canada Inc. | Stereoselective process for the production of dioxolane nucleoside analogues |
| DE10335061B4 (de) * | 2003-07-31 | 2005-11-17 | Wacker-Chemie Gmbh | Verfahren zur Herstellung von OH-geschützten [4-(2,6-damino-9H-purin-9-yl)-1,3-dioxolan-2-yl]methanol-Derivaten |
| CA2554782C (fr) | 2004-02-03 | 2013-08-13 | Emory University | Methodes de fabrication de nucleosides de 1,3-dioxolane |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5190867A (en) * | 1986-05-08 | 1993-03-02 | Shell International Petroleum Company, Ltd. | Process for the preparation of R-2,2-R1,R2 -1,3-dioxolane-4-methanol |
| DD277698A1 (de) * | 1988-12-06 | 1990-04-11 | Ve Forschungszentrum Biotechno | Verfahren zur herstellung von substituierten (s)-1,3-dioxolan-4-carbonsaeureestern aus den racematen |
| US5283346A (en) * | 1989-03-23 | 1994-02-01 | Hoffmann-La Roche Inc. | Dioxolanes |
| US5276151A (en) * | 1990-02-01 | 1994-01-04 | Emory University | Method of synthesis of 1,3-dioxolane nucleosides |
| GB9525606D0 (en) * | 1995-12-14 | 1996-02-14 | Iaf Biochem Int | Method and compositions for the synthesis of dioxolane nucleosides with - configuration |
-
2000
- 2000-02-11 CA CA002362570A patent/CA2362570A1/fr not_active Abandoned
- 2000-02-11 WO PCT/CA2000/000144 patent/WO2000047759A1/fr not_active Ceased
- 2000-02-11 JP JP2000598654A patent/JP2002538780A/ja active Pending
- 2000-02-11 AU AU26532/00A patent/AU2653200A/en not_active Abandoned
- 2000-02-11 EP EP00904756A patent/EP1151133A1/fr not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| AU2653200A (en) | 2000-08-29 |
| EP1151133A1 (fr) | 2001-11-07 |
| WO2000047759A1 (fr) | 2000-08-17 |
| JP2002538780A (ja) | 2002-11-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |