CA1265132A - Processus de synthese organique d'oligosaccharides et de leurs derives - Google Patents

Processus de synthese organique d'oligosaccharides et de leurs derives

Info

Publication number: CA1265132A
Authority: CA; Canada
Prior art keywords: group; groups; unit; formula; process according
Prior art date: 1982-01-15
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

Application number

CA000419417A

Other languages

English (en)

Inventor

Mahmoud Nassr

Maurice Petitou

Jean-Claude Lormeau

Jean Choay

Pierre Sinay

Jean-Claude Jacquinet

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Sanofi Aventis France

Original Assignee

Choay SA

Priority date (The priority date 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 date listed.)

1982-01-15

Filing date

1983-01-13

Publication date

1990-01-30

1982-01-15 Priority claimed from FR8200621A external-priority patent/FR2519987A1/fr

1982-02-01 Priority claimed from FR8201575A external-priority patent/FR2520744A1/fr

1982-02-16 Priority claimed from FR8202526A external-priority patent/FR2521566A1/fr

1982-05-28 Priority claimed from FR8209392A external-priority patent/FR2527614A1/fr

1982-06-22 Priority claimed from FR8210891A external-priority patent/FR2528853A1/fr

1982-06-22 Priority claimed from FR8210892A external-priority patent/FR2528854A1/fr

1982-07-02 Priority claimed from FR8211679A external-priority patent/FR2529557A1/fr

1982-08-06 Priority claimed from FR8213804A external-priority patent/FR2531436A1/fr

1982-09-20 Priority claimed from FR8215803A external-priority patent/FR2533219A1/fr

1982-09-20 Priority claimed from FR8215804A external-priority patent/FR2533220A1/fr

1982-10-27 Priority claimed from FR8218003A external-priority patent/FR2535324A1/fr

1983-01-13 Application filed by Choay SA filed Critical Choay SA

1990-01-30 Publication of CA1265132A publication Critical patent/CA1265132A/fr

1990-01-30 Application granted granted Critical

Status Expired legal-status Critical Current

Links

238000003786 synthesis reaction Methods 0.000 title claims abstract description 95
150000002482 oligosaccharides Chemical class 0.000 title claims abstract description 91
229920001542 oligosaccharide Polymers 0.000 title claims abstract description 84
238000000034 method Methods 0.000 title claims abstract description 61
230000008569 process Effects 0.000 title claims abstract description 48
238000006243 chemical reaction Methods 0.000 claims abstract description 97
239000002253 acid Substances 0.000 claims abstract description 44
MSWZFWKMSRAUBD-IVMDWMLBSA-N glucosamine group Chemical group OC1[C@H](N)[C@@H](O)[C@H](O)[C@H](O1)CO MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 claims abstract description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 160
230000015572 biosynthetic process Effects 0.000 claims description 92
150000002016 disaccharides Chemical class 0.000 claims description 90
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 55
-1 p-methoxybenzoyl group Chemical group 0.000 claims description 43
239000002904 solvent Substances 0.000 claims description 43
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 30
150000002772 monosaccharides Chemical class 0.000 claims description 28
MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical compound N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 claims description 24
230000000875 corresponding effect Effects 0.000 claims description 23
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 21
230000007935 neutral effect Effects 0.000 claims description 21
125000006239 protecting group Chemical group 0.000 claims description 21
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 19
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 19
239000003054 catalyst Substances 0.000 claims description 19
239000003795 chemical substances by application Substances 0.000 claims description 19
150000004044 tetrasaccharides Chemical class 0.000 claims description 18
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
238000009833 condensation Methods 0.000 claims description 17
230000005494 condensation Effects 0.000 claims description 17
125000000524 functional group Chemical group 0.000 claims description 16
IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 claims description 14
AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 claims description 13
229910052799 carbon Inorganic materials 0.000 claims description 13
230000004048 modification Effects 0.000 claims description 13
238000012986 modification Methods 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 13
238000011282 treatment Methods 0.000 claims description 13
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
150000002905 orthoesters Chemical class 0.000 claims description 12
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 11
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 11
125000002252 acyl group Chemical group 0.000 claims description 11
238000006482 condensation reaction Methods 0.000 claims description 11
235000000346 sugar Nutrition 0.000 claims description 11
150000004820 halides Chemical class 0.000 claims description 10
229920000669 heparin Polymers 0.000 claims description 10
229960002897 heparin Drugs 0.000 claims description 10
AEMOLEFTQBMNLQ-CLQWQSTFSA-N l-iduronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@@H](O)[C@@H]1O AEMOLEFTQBMNLQ-CLQWQSTFSA-N 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 8
229960002442 glucosamine Drugs 0.000 claims description 8
QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical group [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 claims description 8
229910052709 silver Inorganic materials 0.000 claims description 7
239000004332 silver Substances 0.000 claims description 7
150000001720 carbohydrates Chemical group 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
NGYIMTKLQULBOO-UHFFFAOYSA-L mercury dibromide Chemical compound Br[Hg]Br NGYIMTKLQULBOO-UHFFFAOYSA-L 0.000 claims description 6
125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 6
125000000547 substituted alkyl group Chemical group 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 5
238000009835 boiling Methods 0.000 claims description 5
ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims description 4
WQZGKKKJIJFFOK-ZNVMLXAYSA-N L-idopyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-ZNVMLXAYSA-N 0.000 claims description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 4
239000003960 organic solvent Substances 0.000 claims description 4
LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 4
229910001958 silver carbonate Inorganic materials 0.000 claims description 4
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims description 4
239000004593 Epoxy Substances 0.000 claims description 3
150000005840 aryl radicals Chemical class 0.000 claims description 3
150000002730 mercury Chemical class 0.000 claims description 3
RTKMFQOHBDVEBC-UHFFFAOYSA-N 3-bromo-3-buten-1-ol Chemical compound OCCC(Br)=C RTKMFQOHBDVEBC-UHFFFAOYSA-N 0.000 claims description 2
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 2
125000004036 acetal group Chemical group 0.000 claims description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 claims description 2
229940075610 mercuric cyanide Drugs 0.000 claims description 2
229910052751 metal Inorganic materials 0.000 claims description 2
239000002184 metal Substances 0.000 claims description 2
230000001681 protective effect Effects 0.000 claims description 2
230000002441 reversible effect Effects 0.000 claims description 2
229910001923 silver oxide Inorganic materials 0.000 claims description 2
230000010933 acylation Effects 0.000 claims 2
238000005917 acylation reaction Methods 0.000 claims 2
230000002152 alkylating effect Effects 0.000 claims 2
230000001371 heparinic effect Effects 0.000 claims 2
WJFVEEAIYIOATH-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine 6-sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](COS(O)(=O)=O)[C@@H](O)[C@@H]1O WJFVEEAIYIOATH-FMDGEEDCSA-N 0.000 claims 1
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
MTDHILKWIRSIHB-QZABAPFNSA-N beta-D-glucosamine 6-sulfate Chemical compound N[C@H]1[C@H](O)O[C@H](COS(O)(=O)=O)[C@@H](O)[C@@H]1O MTDHILKWIRSIHB-QZABAPFNSA-N 0.000 claims 1
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims 1
RXPRRQLKFXBCSJ-UHFFFAOYSA-N dl-Vincamin Natural products C1=CC=C2C(CCN3CCC4)=C5C3C4(CC)CC(O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-UHFFFAOYSA-N 0.000 claims 1
125000003700 epoxy group Chemical group 0.000 claims 1
150000002302 glucosamines Chemical class 0.000 claims 1
238000006557 surface reaction Methods 0.000 claims 1
RXPRRQLKFXBCSJ-GIVPXCGWSA-N vincamine Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-GIVPXCGWSA-N 0.000 claims 1
150000001875 compounds Chemical class 0.000 abstract description 84
239000012634 fragment Substances 0.000 abstract description 7
229920002683 Glycosaminoglycan Polymers 0.000 abstract description 5
230000036647 reaction Effects 0.000 abstract description 4
239000003146 anticoagulant agent Substances 0.000 abstract description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 276
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 212
239000000243 solution Substances 0.000 description 180
239000000203 mixture Substances 0.000 description 153
229960001701 chloroform Drugs 0.000 description 136
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 130
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 121
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 99
239000000047 product Substances 0.000 description 94
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 93
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 68
238000004458 analytical method Methods 0.000 description 64
239000000741 silica gel Substances 0.000 description 62
229910002027 silica gel Inorganic materials 0.000 description 62
239000011541 reaction mixture Substances 0.000 description 60
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 58
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 49
238000002360 preparation method Methods 0.000 description 45
239000006188 syrup Substances 0.000 description 44
235000020357 syrup Nutrition 0.000 description 44
229940093499 ethyl acetate Drugs 0.000 description 40
235000019439 ethyl acetate Nutrition 0.000 description 40
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 37
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 36
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 35
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
238000010828 elution Methods 0.000 description 33
238000001704 evaporation Methods 0.000 description 32
230000008020 evaporation Effects 0.000 description 32
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 32
238000007792 addition Methods 0.000 description 31
239000012071 phase Substances 0.000 description 31
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 29
229910052938 sodium sulfate Inorganic materials 0.000 description 29
235000011152 sodium sulphate Nutrition 0.000 description 29
238000003756 stirring Methods 0.000 description 29
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 28
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 26
239000012074 organic phase Substances 0.000 description 25
125000001309 chloro group Chemical group Cl* 0.000 description 24
238000001816 cooling Methods 0.000 description 23
238000001035 drying Methods 0.000 description 22
239000011734 sodium Substances 0.000 description 21
239000007787 solid Substances 0.000 description 21
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 20
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
238000004587 chromatography analysis Methods 0.000 description 20
238000001914 filtration Methods 0.000 description 20
238000006206 glycosylation reaction Methods 0.000 description 20
229910052708 sodium Inorganic materials 0.000 description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 18
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
150000003254 radicals Chemical class 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-N sodium;hydron;carbonate Chemical compound [Na+].OC(O)=O UIIMBOGNXHQVGW-UHFFFAOYSA-N 0.000 description 18
150000004043 trisaccharides Chemical class 0.000 description 18
238000005670 sulfation reaction Methods 0.000 description 17
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 16
235000011167 hydrochloric acid Nutrition 0.000 description 16
229960000443 hydrochloric acid Drugs 0.000 description 16
239000000126 substance Substances 0.000 description 16
230000019635 sulfation Effects 0.000 description 16
238000005481 NMR spectroscopy Methods 0.000 description 15
239000007864 aqueous solution Substances 0.000 description 15
239000000377 silicon dioxide Substances 0.000 description 15
238000001228 spectrum Methods 0.000 description 15
QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 15
238000010790 dilution Methods 0.000 description 14
239000012895 dilution Substances 0.000 description 14
239000000499 gel Substances 0.000 description 14
238000002329 infrared spectrum Methods 0.000 description 14
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 14
239000000843 powder Substances 0.000 description 14
229960000583 acetic acid Drugs 0.000 description 13
235000011054 acetic acid Nutrition 0.000 description 13
238000004821 distillation Methods 0.000 description 13
238000006467 substitution reaction Methods 0.000 description 13
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
230000013595 glycosylation Effects 0.000 description 12
239000000543 intermediate Substances 0.000 description 12
239000002808 molecular sieve Substances 0.000 description 12
239000011347 resin Substances 0.000 description 12
229920005989 resin Polymers 0.000 description 12
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 12
229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Inorganic materials O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 12
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 12
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 12
BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 11
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 11
101150041968 CDC13 gene Proteins 0.000 description 11
239000012300 argon atmosphere Substances 0.000 description 11
229910052739 hydrogen Inorganic materials 0.000 description 11
229920001467 poly(styrenesulfonates) Polymers 0.000 description 11
150000003839 salts Chemical class 0.000 description 11
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 10
229930014626 natural product Natural products 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 10
235000017557 sodium bicarbonate Nutrition 0.000 description 10
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 10
WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 9
230000006870 function Effects 0.000 description 9
239000002243 precursor Substances 0.000 description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
150000001242 acetic acid derivatives Chemical class 0.000 description 8
238000006640 acetylation reaction Methods 0.000 description 8
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 8
239000011521 glass Substances 0.000 description 8
239000001257 hydrogen Substances 0.000 description 8
238000005984 hydrogenation reaction Methods 0.000 description 8
239000005457 ice water Substances 0.000 description 8
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 8
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 7
229920005654 Sephadex Polymers 0.000 description 7
239000012507 Sephadex™ Substances 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
230000000903 blocking effect Effects 0.000 description 7
150000001768 cations Chemical class 0.000 description 7
239000003153 chemical reaction reagent Substances 0.000 description 7
238000011161 development Methods 0.000 description 7
230000000694 effects Effects 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
150000002338 glycosides Chemical group 0.000 description 7
230000011987 methylation Effects 0.000 description 7
238000007069 methylation reaction Methods 0.000 description 7
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
229910021653 sulphate ion Inorganic materials 0.000 description 7
238000012360 testing method Methods 0.000 description 7
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 7
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Landscapes

Polysaccharides And Polysaccharide Derivatives (AREA)
Saccharide Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

CA000419417A 1982-01-15 1983-01-13 Processus de synthese organique d'oligosaccharides et de leurs derives Expired CA1265132A (fr)

Applications Claiming Priority (22)

Application Number	Priority Date	Filing Date	Title
FR8200621A FR2519987A1 (fr)	1982-01-15	1982-01-15	Trisaccharides a structures d-glucosamine, acide d-glucuronique, d-glucosamine et leur preparation
FR8200621		1982-01-15
FR8201575A FR2520744A1 (fr)	1982-02-01	1982-02-01	Nouveaux derives d'osides et leur preparation
FR8201575		1982-02-01
FR8202526		1982-02-16
FR8202526A FR2521566A1 (fr)	1982-02-16	1982-02-16	Nouveaux tetrasaccharides et leur preparation
FR8209392		1982-05-28
FR8209392A FR2527614A1 (fr)	1982-05-28	1982-05-28	Nouveaux derives de disaccharides formes de motifs a structure respectivement glucosamine et acide uronique et leur preparation
FR8210891A FR2528853A1 (fr)	1982-06-22	1982-06-22	Nouveaux trisaccharides a structure d-glucosamine, acide l-iduronique, d-glucosamine et leur preparation
FR8210892		1982-06-22
FR8210891		1982-06-22
FR8210892A FR2528854A1 (fr)	1982-06-22	1982-06-22	Nouveaux derives de tetrasaccharides et leur preparation
FR8211679		1982-07-02
FR8211679A FR2529557A1 (fr)	1982-07-02	1982-07-02	Nouveaux disaccharides contenant un motif a-l-idopyranose, et leur preparation
FR8213804		1982-08-06
FR8213804A FR2531436A1 (fr)	1982-08-06	1982-08-06	Pentasaccharides substitues possedant des proprietes biologiques, leur preparation et leurs applications en tant que medicaments
FR8215803A FR2533219A1 (fr)	1982-09-20	1982-09-20	Nouveaux disaccharides formes de motifs a structure d-glucosamine et acide l-iduronique et procede pour leur preparation
FR8215804A FR2533220A1 (fr)	1982-09-20	1982-09-20	Nouveaux disaccharides formes de motifs a structure acide d-glucuronique et d-glucosamine et procede pour leur preparation
FR8215803		1982-09-20
FR8215804		1982-09-20
FR8218003A FR2535324A1 (fr)	1982-10-27	1982-10-27	Station perfectionnee pour l'epuration d'eaux usees
FR8218003		1982-10-27

Publications (1)

Publication Number	Publication Date
CA1265132A true CA1265132A (fr)	1990-01-30

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ID=27581614

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000419417A Expired CA1265132A (fr)	1982-01-15	1983-01-13	Processus de synthese organique d'oligosaccharides et de leurs derives

Country Status (5)

Country	Link
JP (1)	JP2510454B2 (fr)
AT (1)	ATE33496T1 (fr)
CA (1)	CA1265132A (fr)
DE (2)	DE3376265D1 (fr)
DK (1)	DK174348B1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US10072039B2 (en)	2013-07-25	2018-09-11	Scinopharm Taiwan, Ltd.	Process for the production of Fondaparinux sodium

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2919206C (fr) *	2013-07-25	2018-09-25	Scinopharm Taiwan, Ltd.	Procede de production de fondaparinux sodium

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1136620A (fr) *	1979-01-08	1982-11-30	Ulf P.F. Lindahl	Fragments d'heparine ayant une activite anticoagulante selective
AT377493B (de) *	1979-09-19	1985-03-25	Wiedmer Ernst	Schraubverschluss mit einem garantiering fuer einen behaelter zur anzeige der erstmaligen oeffnung des behaelters
IL61201A (en) *	1979-10-05	1984-09-30	Choay Sa	Oligosaccharides having no more than 8 saccharide moieties,their obtention from heparin and pharmaceutical compositions containing them
FR2504535B1 (fr) *	1981-04-28	1987-08-14	Choay Sa	Disaccharides derives d'un acide uronique et d'une glucosamine et compositions pharmaceutiques les contenant pour le controle de la coagulation sanguine

1983
- 1983-01-13 CA CA000419417A patent/CA1265132A/fr not_active Expired
- 1983-01-14 DK DK14383A patent/DK174348B1/da not_active IP Right Cessation
- 1983-01-17 AT AT83400110T patent/ATE33496T1/de active
- 1983-01-17 DE DE8383400110T patent/DE3376265D1/de not_active Expired
- 1983-01-17 DE DE2002199025 patent/DE10299025I2/de active Active
1992
- 1992-04-08 JP JP4115407A patent/JP2510454B2/ja not_active Expired - Lifetime

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US10072039B2 (en)	2013-07-25	2018-09-11	Scinopharm Taiwan, Ltd.	Process for the production of Fondaparinux sodium

Also Published As

Publication number	Publication date
DK14383A (da)	1983-07-16
JP2510454B2 (ja)	1996-06-26
DE3376265D1 (en)	1988-05-19
DK174348B1 (da)	2002-12-23
ATE33496T1 (de)	1988-04-15
DK14383D0 (da)	1983-01-14
DE10299025I2 (de)	2002-11-07
JPH05331182A (ja)	1993-12-14

Legal Events

Date	Code	Title	Description
2007-01-30	MKEX	Expiry

Publication	Publication Date	Title
US4818816A (en)	1989-04-04	Process for the organic synthesis of oligosaccharides and derivatives thereof
Petitou et al.	1986	Synthesis of heparin fragments. A chemical synthesis of the pentasaccharide O-(2-deoxy-2-sulfamido-6-O-sulfo-α-d-glucopyranosyl)-(1→ 4)-O-(β-d-glucopyranosyluronic acid)-(1→ 4)-O-(2-deoxy-2-sulfamido-3, 6-di-O-sulfo-α-d-glucopyranosyl)-(1→ 4)-O-(2-O-sulfo-α-l-idopyranosyluronic acid)-(1→ 4)-2-deoxy-2-sulfamido-6-O-sulfo-d-glucopyranose decasodium salt, a heparin fragment having high affinity for antithrombin III
JP2510925B2 (ja)	1996-06-26	ガラクトサミン−ウロン酸基本（モチ―フ）を含むオリゴ糖類及びそれらの生物学的用途
DK171678B1 (da)	1997-03-10	Pentasaccharider og mellemprodukter herfor
Van Boeckel et al.	1985	Synthesis of a pentasaccharide corresponding to the antithrombin III binding fragment of heparin
Jacquinet et al.	1984	Synthesis of heparin fragments. A chemical synthesis of the trisaccharide O-(2-deoxy-2-sulfamido-3, 6-di-O-sulfo-α-d-glucopyranosyl)-(1→ 4)-O-(2-O-sulfo-α-l-idopyranosyluronic acid)-(1→ 4)-2-deoxy-2-sulfamido-6-O-sulfo-d-glucopyranose heptasodium salt
AU2002331426B2 (en)	2008-01-10	Synthetic heparin pentasaccharides
EP0084999B1 (fr)	1988-04-13	Procédé de synthèse organique d'oligosaccharides, correspondant à des fragments de muco-polysaccharides naturels, nouveaux oligosaccharides obtenus et leurs applications biologiques
AU726679B2 (en)	2000-11-16	Synthetic polysaccharides, preparation method therefor and pharmaceutical compositions containing same
US5543403A (en)	1996-08-06	Sulfated glycosaminoglycanoid derivatives of the heparin and heparan sulfate type
Petitou et al.	1988	Binding of heparin to antithrombin III: a chemical proof of the critical role played by a 3-sulfated 2-amino-2-deoxy-D-glucose residue
US4987223A (en)	1991-01-22	Derivatives of the uronic acid
US4801583A (en)	1989-01-31	Oligosaccharides and their biological applications
WO2013003001A1 (fr)	2013-01-03	Procédé de préparation d'héparinoïdes et d'intermédiaires utiles pour leur synthèse
HU215152B (hu)	2000-11-28	Eljárás pentaszacharid egységet tartalmazó szénhidrátszármazékok és ezeket tartalmazó gyógyszerkészítmények előállítására
NO179452B (no)	1996-07-01	Sulfaterte glukosamin-glukanoid-derivater
Jacquinet et al.	1987	Synthesis of dermatan sulfate fragments: A chemical synthesis of methyl 2-acetamido-2-deoxy-3-O-(α-lidopyranosyluronic acid)-4-O-sulfo-β-d-galactopyranoside disodium salt and its non-sulfated analogue
DK174284B1 (da)	2002-11-11	Biologisk aktive tetrasaccharider
Marra et al.	1989	Synthesis of disaccharide fragments of dermatan sulfate
Petitou et al.	1999	New synthetic heparin mimetics able to inhibit thrombin and factor Xa
NO329903B1 (no)	2011-01-24	Syntetiske polysakkarider, farmasoytiske preparater inneholdende slike samt anvendelse derav
Imoto et al.	1988	Synthetic approach to bacterial lipopolysaccharide, preparation of trisaccharide part structures containing KDO and 1-dephospho lipid A
Rochepeau-Jobron et al.	1997	Synthesis of O-(2-O-sulfo-α-l-idopyranosyluronic acid)-(1→ 3)-2-acetamido-2-deoxy-4-O-sulfo-d-galactopyranose trisodium salt, a disaccharide fragment of dermatan sulfate
US5773605A (en)	1998-06-30	Sulfated glycosaminoglycanoid derivatives of the heparin sulfate type
CA1265132A (fr)	1990-01-30	Processus de synthese organique d'oligosaccharides et de leurs derives

CA1265132A - Processus de synthese organique d'oligosaccharides et de leurs derives - Google Patents

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Publications (1)

Family

ID=27581614

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Cited By (1)

Families Citing this family (1)

Family Cites Families (4)

Cited By (1)

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