DK164050B - 4-benzyloxy-3-pyrrolin-2-on samt anvendelse deraf til fremstilling af tetramsyre - Google Patents
4-benzyloxy-3-pyrrolin-2-on samt anvendelse deraf til fremstilling af tetramsyre Download PDFInfo
- Publication number
- DK164050B DK164050B DK325287A DK325287A DK164050B DK 164050 B DK164050 B DK 164050B DK 325287 A DK325287 A DK 325287A DK 325287 A DK325287 A DK 325287A DK 164050 B DK164050 B DK 164050B
- Authority
- DK
- Denmark
- Prior art keywords
- benzyloxy
- acid
- preparation
- pyrrolin
- tetric
- Prior art date
Links
- FIPLVTFTJOOADU-UHFFFAOYSA-N 3-phenylmethoxy-1,2-dihydropyrrol-5-one Chemical compound O=C1NCC(OCC=2C=CC=CC=2)=C1 FIPLVTFTJOOADU-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000002253 acid Substances 0.000 title 1
- RUXHWBMJNBBYNL-UHFFFAOYSA-N 3-hydroxy-1,2-dihydropyrrol-5-one Chemical compound OC1=CC(=O)NC1 RUXHWBMJNBBYNL-UHFFFAOYSA-N 0.000 claims abstract description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 6
- 239000013067 intermediate product Substances 0.000 abstract 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 235000019445 benzyl alcohol Nutrition 0.000 description 5
- TXKQBYYDTLOLHA-UHFFFAOYSA-N 3-methoxy-1,2-dihydropyrrol-5-one Chemical compound COC1=CC(=O)NC1 TXKQBYYDTLOLHA-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- -1 ethoxycarbonylacetyl Chemical group 0.000 description 2
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- HGINADPHJQTSKN-UHFFFAOYSA-N Monoethyl malonic acid Chemical compound CCOC(=O)CC(O)=O HGINADPHJQTSKN-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002085 enols Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- GQEDOGKXSMQIRV-UHFFFAOYSA-N methyl 2,4-dioxopyrrolidine-3-carboxylate Chemical compound COC(=O)C1C(=O)CNC1=O GQEDOGKXSMQIRV-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- UTZNELIJGYWMKS-UHFFFAOYSA-N phenylmethanol;hydrate Chemical compound O.OCC1=CC=CC=C1 UTZNELIJGYWMKS-UHFFFAOYSA-N 0.000 description 1
- DOQJUNNMZNNQAD-UHFFFAOYSA-N pyrrolidine-2,4-dione Chemical compound O=C1CNC(=O)C1 DOQJUNNMZNNQAD-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
- C07D207/38—2-Pyrrolones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Pyridine Compounds (AREA)
Description
Opfindelsen angår den hidtil ukendte 4-benzyloxy-3-pyrrol- in-2-on med formlen
DK 164050 B
H
5 samt anvendelsen deraf til fremstilling af tetramsyre med formlen h.
Nir
H
Tetramsyre er et værdifuldt udgangsmateriale ved fremstillingen af Ø-lactamer, som igen anvendes til fremstillin-10 gen af virksomme antibiotika, jf. G. Lowe, J. Chem. Soc., Perkin Trans. I, 1973, 2907.
Der er mangel på fordelagtige fremgangsmåder til fremstilling af tetramsyre. Fra G. Lowe, J. Chem. Soc., Perkin Trans. I, 1973, 2909 er det således kendt at omsætte 15 malonsyremonoethylester med glycinethylester i nærværelse af dicyclohexylcarbodiimid til dannelse af N-(ethoxycarbonyl-acetyl)-glycinethylester, som i et andet trin ringsluttes med en base til 2,4-dioxopyrrolidin-3-carboxylsyremethyl-ester, der til sidst decarboxyleres til tetramsyre. 1
Den væsentligste ulempe ved denne fremgangsmåde er imidlertid den nødvendige, ekstremt høje fortynding af reaktionsopløsningen i det sidste trin (3,39 g til 2,5 1 = 0,1%'s opløsning), som udelukker en økonomisk fremgangsmåde i stor målestok.
DK 164050 B
2
Det er derfor formålet med opfindelsen at tilvejebringe en fremgangsmåde til fremstilling af tetramsyre, som ikke har disse ulemper.
5 Dette opnås på overraskende enkel måde ved anvendelse af det hidtil ukendte, let tilgængelige mellemprodukt, 4-benzyloxy- 3- pyrrolin-2-on.
4- Benzyloxy-3-pyrrolin-2-on kan fremstilles ved syrekatalyseret omsætning af 4-alkoxy-3-pyrrolin-2-oner med benzyl- 10 alkohol. 4-Alkoxy-3-pyrrolin-2-onerne kan fremstilles på enkel måde ifølge en kendt fremgangsmåde ud fra 4-halogen-aceteddikeestere jf. beskrivelsen til CH-patentansøgning nr. 4119/85.
Som udgangsmaterialer anvendes fortrinsvis 4-methoxy-3-pyr-15 rolin-2-on. Som syrer til omsætningen anvendes hensigtsmæssigt vandfri uorganiske syrer, f.eks. svovlsyre, eller sulfonsyrer, f.eks. methansulfonsyre. Der anvendes fortrinsvis methansulfonsyre. Denne anvendes i katalytiske mængder på hensigtmæssigt 5-20 mol-%, fortrinsvis 5-10 20 mol-%.
Reaktanten benzylalkohol anvendes hensigtmæssigt i et overskud på 50-200%, beregnet på den anvendte 4-alkoxy-3-pyrrolin-2-on.
Fordelagtigt anvendes benzylalkohol samtidig som opløsnings-25 middel.
Omsætningen gennemføres fortrinsvis ved temperaturer mellem 60 og 100°C, fortrinsvis mellem 70 og 90°C.
Omsætningen gennemføres fortrinsvis under nedsat tryk, især mellem 1 og 50 mbar, for at fjerne de fraspaltede lavere 30 alkoholer fra ligevægtssystemet. Efter en reaktionstid på fra ca. 20 til ca. 30 timer kan 4-benzyloxy-3-pyrrolin-2-on 3 isoleres på sædvanlig måde, f.eks. ved azeotrop afdampning af overskud af benzylalkohol og eventuelt ved efterfølgende krystallisation.
5 Anvendelsen ifølge opfindelsen er ejendommelig ved, at 4-benzyloxy-3-pyrrolin-2-on underkastes en katalytisk hydrogenolyse. Ved denne omsætning dannes tetramsyre. En særlig velegnet katalysator er palladium i en mængde på fortrinsvis 5-20% på kul.
10 Omsætningen gennemføres fordelagtigt i vandfrie, polære, aprotiske opløsningsmidler. Fortrinsvis anvendes tetra-hydrofuran, dioxan eller dimethylformamid som opløsningsmiddel .
Reaktionstemperaturerne bevæger sig hensigtmæssigt mellem 0 15 og 40 °C og reaktions trykkene mellem 1 og 20 bar.
Efter sædvanlige oparbejdning, som er afhængig af tryk og temperatur, og som kan gennemføres i løbet af 5-10 timer, opnås tetramsyren i næsten kvantitativt udbytte.
Opfindelsen illustreres nærmere ved hjælp af de 20 efterfølgende eksempler.
Eksempel 1
Fremstilling af 4-benzyloxy-3-pyrrolin-2-on Til 5,7 g (50 mmol) 4-methoxy-3-pyrrolin-2-on og 10,8 g (100 mmol) benzylalkohol sættes 0,4 g (4 mmol) methansulfonsyre, 25 og blandingen omrøres i 24 timer ved 80°C og 20 mbar. Derefter sættes 50 ml isvand og 100 ml methylenchlorid til reaktionsblandingen, hvorpå der neutraliseres med 4 ml mættet natriumhydrogencarbonatopløsning. Den vandige fase ekstrahe-res yderligere med 2 x 50 ml methylenchlorid. Efter tørring 30 af den organiske fase med natriumsulfat og afdampning af opløsningsmidlet sættes 150 ml isvand til remanensen,
DK 164050 B
4 blandingen opvarmes til 100°C, og 100 ml vand-benzylalkohol afdestilleres azeotropt. De ved afkøling udfældede krystaller omkrystalliseres varmt fra 50 ml toluen.
5 Man får 6,7 g hvidt, krystallinsk produkt med et smeltepunkt på 147-148°C.
NMR: (300 MHz, DMSO-dg) δ i ppm 7,38 (m, 5H), 6,20 (bred, s, IH), 5,16 (s, IH), 4,98 (s, 2H), 3,98 (s, 2H).
10 NMS (70 eV): (M+, 40), 172 (18), 132 (51), 91 (100).
Eksempel 2
Fremstilling af 2,4-dioxopyrrolidin (tetramsyre) 1,0 g (5,3 mmol) 4-benzyloxy-3-pyrrolin-2-on opløses i 50 ml tetrahydrofuran, hvorpå der hydrogenolyseres i nærværelse af 15 100 mg Pd/c 5% i 6 timer ved stuetemperatur og et tryk på 10 bar. Derefter frafiltreres katalysatoren, og filtratet inddampes til tørhed på en rotationsfordamper.
Man får 500 mg hvidt, krystallinsk produkt med et smeltepunkt på 120°C (over 120°C bliver produktet atter fast). 1 NMR: (300 MHz, DMSO-dg) δ i ppm
Enolform: 11,28 (s, IH), 7,11 (bred, s, IH), 4,76 (s, IH), 3,74 (s, 2H).
Ketoform: 8,25 (bred, s IH), 3,78 (s, 2H), 2,93 (s, 2H).
MS (70 eV): 99 (M+, 32), 71 (78(, 43 (58), 42 (100).
Claims (4)
1. 4-Benzyloxy-3-pyrrolin-2-on, kendetegnet ved formlen ÆVcHjP O· H
2. Anvendelse af forbindelsen ifølge krav 1 til fremstilling af tetramsyre med formlen h. H kendetegnet ved, at 4-benzyloxy-3-pyrrolin-2-on underkastes 10 en katalytisk hydrogenolyse.
3. Anvendelse ifølge krav 2, kendetegnet ved, at man som katalysator anvender palladium.
4. Anvendelse ifølge krav 2 og 3, kendetegnet ved, at man arbejder ved temperaturer på 0-40°C og tryk på 1-20 bar.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH2566/86A CH668422A5 (de) | 1986-06-26 | 1986-06-26 | 4-benzyloxy-3-pyrrolin-2-on, dessen herstellung und verwendung zur synthese von tetramsaeure. |
| CH256686 | 1986-06-26 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK325287D0 DK325287D0 (da) | 1987-06-25 |
| DK325287A DK325287A (da) | 1987-12-27 |
| DK164050B true DK164050B (da) | 1992-05-04 |
| DK164050C DK164050C (da) | 1992-09-28 |
Family
ID=4236686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK325287A DK164050C (da) | 1986-06-26 | 1987-06-25 | 4-benzyloxy-3-pyrrolin-2-on samt anvendelse deraf til fremstilling af tetramsyre |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US4855451A (da) |
| EP (1) | EP0252363B1 (da) |
| JP (1) | JPH0737444B2 (da) |
| AT (1) | ATE59635T1 (da) |
| CA (2) | CA1277670C (da) |
| CH (1) | CH668422A5 (da) |
| CS (1) | CS269994B2 (da) |
| DE (1) | DE3766898D1 (da) |
| DK (1) | DK164050C (da) |
| ES (1) | ES2019603B3 (da) |
| HU (1) | HUT44510A (da) |
| IE (1) | IE60334B1 (da) |
| IL (1) | IL82936A (da) |
| NO (1) | NO172689C (da) |
| SU (1) | SU1470179A3 (da) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02115162A (ja) * | 1988-09-06 | 1990-04-27 | Lonza Ag | ５―アルキルテトラム酸およびその製造方法 |
| JPH0814219B2 (ja) * | 1991-12-04 | 1996-02-14 | 株式会社中西エンジニアリング | 内倒れ式上下動窓 |
| US7741327B2 (en) | 2008-04-16 | 2010-06-22 | Hoffmann-La Roche Inc. | Pyrrolidinone glucokinase activators |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2784191A (en) * | 1957-03-05 | Process for the production of lactams | ||
| US2535010A (en) * | 1948-10-02 | 1950-12-19 | Rohm & Haas | Transetherification of beta-ethersubstituted esters |
| DE850007C (de) * | 1950-12-22 | 1952-09-22 | Basf Ag | Verfahren zur Herstellung von N-Aryl-ª‡-pyrrolidonen |
| US3299095A (en) * | 1964-04-16 | 1967-01-17 | Merck & Co Inc | 1-benzyl tetramic acid derivatives |
| JPS4941521A (da) * | 1972-06-02 | 1974-04-18 | ||
| IT1045043B (it) * | 1975-08-13 | 1980-04-21 | Isf Spa | Derivati pirrolidinici |
| IT1075564B (it) * | 1977-02-11 | 1985-04-22 | Isf Spa | Procedimento per la preparazione di derivati pirrolidinici |
| IT1075280B (it) * | 1977-02-11 | 1985-04-22 | Isf Spa | Procedimento per la preparazione di derivati pirrolidinici |
| JPS5812272B2 (ja) * | 1981-04-28 | 1983-03-07 | 電気化学工業株式会社 | ４−ヒドロキシ−２−ピロリドンの製造法 |
| FI83510C (fi) * | 1985-02-22 | 1991-07-25 | Ciba Geigy Ag | Foerfarande foer framstaellning av nya, terapeutiskt anvaendbara bi-2h- pyrroli(di)ndioner. |
-
1986
- 1986-06-26 CH CH2566/86A patent/CH668422A5/de not_active IP Right Cessation
-
1987
- 1987-06-03 IE IE146887A patent/IE60334B1/en not_active IP Right Cessation
- 1987-06-10 US US07/060,338 patent/US4855451A/en not_active Expired - Fee Related
- 1987-06-17 SU SU874202756A patent/SU1470179A3/ru active
- 1987-06-19 CA CA000540174A patent/CA1277670C/en not_active Expired - Fee Related
- 1987-06-21 IL IL82936A patent/IL82936A/xx not_active IP Right Cessation
- 1987-06-22 JP JP62155253A patent/JPH0737444B2/ja not_active Expired - Lifetime
- 1987-06-23 EP EP87108974A patent/EP0252363B1/de not_active Expired - Lifetime
- 1987-06-23 DE DE8787108974T patent/DE3766898D1/de not_active Expired - Fee Related
- 1987-06-23 ES ES87108974T patent/ES2019603B3/es not_active Expired - Lifetime
- 1987-06-23 AT AT87108974T patent/ATE59635T1/de not_active IP Right Cessation
- 1987-06-24 CS CS874704A patent/CS269994B2/cs unknown
- 1987-06-25 NO NO872670A patent/NO172689C/no unknown
- 1987-06-25 DK DK325287A patent/DK164050C/da not_active IP Right Cessation
- 1987-06-25 HU HU872884A patent/HUT44510A/hu unknown
-
1988
- 1988-04-28 US US07/187,547 patent/US4812578A/en not_active Expired - Fee Related
-
1990
- 1990-08-09 CA CA000615813A patent/CA1304385C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| IE60334B1 (en) | 1994-06-29 |
| IL82936A0 (en) | 1987-12-20 |
| EP0252363A1 (de) | 1988-01-13 |
| DK164050C (da) | 1992-09-28 |
| CH668422A5 (de) | 1988-12-30 |
| CA1277670C (en) | 1990-12-11 |
| EP0252363B1 (de) | 1991-01-02 |
| IL82936A (en) | 1991-01-31 |
| NO172689B (no) | 1993-05-18 |
| DK325287A (da) | 1987-12-27 |
| CS470487A2 (en) | 1989-09-12 |
| NO872670L (no) | 1987-12-28 |
| US4812578A (en) | 1989-03-14 |
| NO172689C (no) | 1993-08-25 |
| JPH0737444B2 (ja) | 1995-04-26 |
| HUT44510A (en) | 1988-03-28 |
| ATE59635T1 (de) | 1991-01-15 |
| CS269994B2 (en) | 1990-05-14 |
| DE3766898D1 (de) | 1991-02-07 |
| IE871468L (en) | 1987-12-26 |
| JPS638367A (ja) | 1988-01-14 |
| ES2019603B3 (es) | 1991-07-01 |
| SU1470179A3 (ru) | 1989-03-30 |
| US4855451A (en) | 1989-08-08 |
| CA1304385C (en) | 1992-06-30 |
| DK325287D0 (da) | 1987-06-25 |
| NO872670D0 (no) | 1987-06-25 |
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