NO744591L - - Google Patents
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- Publication number
- NO744591L NO744591L NO744591A NO744591A NO744591L NO 744591 L NO744591 L NO 744591L NO 744591 A NO744591 A NO 744591A NO 744591 A NO744591 A NO 744591A NO 744591 L NO744591 L NO 744591L
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- carboxylic acid
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- 238000000034 method Methods 0.000 claims abstract description 14
- 230000002255 enzymatic effect Effects 0.000 claims abstract description 5
- 229930182555 Penicillin Natural products 0.000 claims abstract description 4
- 229930186147 Cephalosporin Natural products 0.000 claims abstract description 3
- 229940124587 cephalosporin Drugs 0.000 claims abstract description 3
- 150000001780 cephalosporins Chemical class 0.000 claims abstract description 3
- 150000002960 penicillins Chemical class 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 239000000835 fiber Substances 0.000 claims description 17
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 108010073038 Penicillin Amidase Proteins 0.000 claims description 5
- 229920002284 Cellulose triacetate Polymers 0.000 claims description 4
- NNLVGZFZQQXQNW-ADJNRHBOSA-N [(2r,3r,4s,5r,6s)-4,5-diacetyloxy-3-[(2s,3r,4s,5r,6r)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6s)-4,5,6-triacetyloxy-2-(acetyloxymethyl)oxan-3-yl]oxyoxan-2-yl]methyl acetate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](OC(C)=O)[C@H]1OC(C)=O)O[C@H]1[C@@H]([C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(C)=O)O1)OC(C)=O)COC(=O)C)[C@@H]1[C@@H](COC(C)=O)O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O NNLVGZFZQQXQNW-ADJNRHBOSA-N 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 4
- 229940088710 antibiotic agent Drugs 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical group C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims description 3
- 229960003022 amoxicillin Drugs 0.000 claims description 3
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 241000588724 Escherichia coli Species 0.000 claims 1
- 230000003115 biocidal effect Effects 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- NVIAYEIXYQCDAN-UHFFFAOYSA-N 7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)C(N)C12 NVIAYEIXYQCDAN-UHFFFAOYSA-N 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 238000003756 stirring Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 5
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 description 4
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- NVIAYEIXYQCDAN-CLZZGJSISA-N 7beta-aminodeacetoxycephalosporanic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](N)[C@@H]12 NVIAYEIXYQCDAN-CLZZGJSISA-N 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108700023418 Amidases Proteins 0.000 description 1
- ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- 102000005922 amidase Human genes 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CVWJDUUVFSVART-UHFFFAOYSA-N ethyl 2-amino-2-(4-hydroxyphenyl)acetate Chemical compound CCOC(=O)C(N)C1=CC=C(O)C=C1 CVWJDUUVFSVART-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 229950009506 penicillinase Drugs 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
- 229920000642 polymer Polymers 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000002023 wood Substances 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
- C12P35/00—Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin
- C12P35/04—Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin by acylation of the substituent in the 7 position
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
- C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
- C12N11/04—Enzymes or microbial cells immobilised on or in an organic carrier entrapped within the carrier, e.g. gel or hollow fibres
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Cephalosporin Compounds (AREA)
Abstract
Fremgangsmåte ved enzymatisk framstilling av hal vsyn tett ske penicilliner og cefalosporiner."-Procedure for the enzymatic preparation of semi-viscous penicillins and cephalosporins. "-
Description
Foreliggende oppfinnelse vedrorer en fremgangsmåte for enzymatisk syntese av halvsyntetiske penicillinet .dg cefålosporiher-ved. Æjélp av en uoppløselig acylase. The present invention relates to a method for the enzymatic synthesis of semi-synthetic penicillin .dg cephalosporiher-wood. Aid of an insoluble acylase.
Viktigheten av de halvsyntetiske derivater av penicilliner og cefalosporiner er i de senere år blitt alminnelig kjent. Disse forbindelser anvendes i stor utstrekning i farmakologien i stedet for de antibiotika som ikke er penicillinaseslkre og de er derfor ikke særlig effektive. Disse produkter kan oppnås ved hjelp av en kjemisk eller enzymatisk syntese. The importance of the semi-synthetic derivatives of penicillins and cephalosporins has become generally known in recent years. These compounds are used to a large extent in pharmacology instead of the antibiotics which are not penicillinase sensitive and are therefore not very effective. These products can be obtained by means of a chemical or enzymatic synthesis.
Den kjemiske syntese, med unntagelse av den som vedrorer fremstilling av ampicillin, gir ikke gode utbytter og krever anvendelse av dyre reaksjonskomponenter og et stort antall trinn. The chemical synthesis, with the exception of that relating to the production of ampicillin, does not give good yields and requires the use of expensive reaction components and a large number of steps.
Den e^2- ymati.ske syntese kan gjennomføres ved hjelp av celler eller av et mer eller mindre renset ekstrahert penicillin-acylaseenzyra. Den gjennomføres vanlig ved hjelp av celler da det rensede enzym The e^2-ymatic synthesis can be carried out with the help of cells or by a more or less purified extracted penicillin acylase enzyme. It is usually carried out using cells as the purified enzyme
er så dyrt at det merkbart påvirker prosessens lønnsomhet. En vesentlig mangel ved den mikrobielle syntese skyldes det forhold at produktet i den endelige reaksjonsblanding befinner seg sammen med store mengder av forurensende proteinmaterial som nødvendig-gjor anvendelse av meget raffinerte og dyre metoder for rensingen. På den annen side er denne rensing absolutt nødvendig for å fjerne de minste spor av protelnforurensninger som hvis de er til stede i sluttproduktet kan bevirke kraftige allergiske reaksjoner. is so expensive that it noticeably affects the profitability of the process. A significant shortcoming of the microbial synthesis is due to the fact that the product in the final reaction mixture is together with large amounts of contaminating protein material which necessitates the use of highly refined and expensive methods for purification. On the other hand, this purification is absolutely necessary to remove the smallest traces of protein contaminants which, if present in the final product, can cause severe allergic reactions.
Den foreliggende roppfinnelse vedrorer enzymatisk syntese hvor det anvendes pénicillin-acylase innesluttet i porøse fibere i henhold til en metodikk som er beskrevet i italiensk patentskrift 836.462 The present invention relates to enzymatic synthesis where penicillin acylase enclosed in porous fibers is used according to a methodology described in Italian patent document 836,462
Viktige særegenheter ved den foreliggende oppfinnelse er:Important features of the present invention are:
a) anvendelse av fibere sont tilfører en stor mengde enzym for å gjennomføre en hurtig syntese av produktene. b) Muligheter for lett fraskilling av enzymet fra reaksjonsblandingen slik at uønskede spaltingsreaksjoner ilske opptrer. c) Produktet er ikke forurenset^da proteinet ikke kan passere ut fra de fiberhulrom hvori det inneholdes. *\ d) Kontinuerlig fornyet anvendelse av det innesluttede enzym som medfører opplagte fordeler for prosessens lønnsomhet. a) the use of fibers adds a large amount of enzyme to carry out a rapid synthesis of the products. b) Possibilities for easy separation of the enzyme from the reaction mixture so that undesired cleavage reactions occur. c) The product is not contaminated, as the protein cannot pass out of the fiber cavities in which it is contained. *\ d) Continually renewed use of the contained enzyme which entails obvious advantages for the profitability of the process.
Reaksjonen foregår mellom et utgangscaaterial som kan fremstilles ved hydrolyse av de naturlige antibiotika eller derivater" derav (e-aminopenicillar^syre 7-aminodaf aloapo/ aasyre) og -en -karboksyl-syre hvis karboksylgruppe kan aktiveres f .eks. ved hjelp av The reaction takes place between a starting material that can be produced by hydrolysis of the natural antibiotics or derivatives thereof (e-aminopenicillar^ acid 7-aminodaphaloapo/aa acid) and -a -carboxylic acid whose carboxyl group can be activated, e.g. by means of
ester eller amid, slik at reaksjonen påskyndes. ester or amide, so that the reaction is accelerated.
Temperaturen kan utgjøre fra 0 til 50°C>foretruktet omtrentThe temperature may be from 0 to 50°C>preferably approximately
25°C, og pH er fra 4,0 til 9,0 og foretrukket omtrent 7. 25°C, and the pH is from 4.0 to 9.0 and preferably about 7.
Realts j onen gjennomføres ved å bringe fiber ene som inneholder The realts j ion is carried out by bringing fiber ene that contains
enzymet i kontakt med reaksjonsblandingen. Da denne er et heterogent system må en kraftig omrøring gjennomføres for å the enzyme in contact with the reaction mixture. As this is a heterogeneous system, vigorous stirring must be carried out to
unngå diffusjonsfenomener.ved grense-sjiktene.avoid diffusion phenomena at the boundary layers.
Forskjellige reaktor typer kan anvendes og en meget enkel reaktor som ble anvendt utgjøres av en kolonne fylt med de enzymholdige fibere og hvorigjennom oppløsningen resifekuleres ved hjelp av en Different reactor types can be used and a very simple reactor that was used consists of a column filled with the enzyme-containing fibers and through which the solution is recycled using a
pumpe i den tid som er nødvendig for å oppnå den høyeste;omdannelse. pump for the time necessary to achieve the highest conversion.
De følgende eksempler illustrer oppfinnelsen.The following examples illustrate the invention.
Eksempel 1Example 1
Fenicillin-acyiase ble ekstrahert og renset fra Sscherichia Coli,. stammen av ATCC 9637, og innesluttet i cellulosetriacetatfibere i henhold til den metode som er beskrevet i italiensk patentskrift 836.462 slik at det ble oppnådd fibere inneholdende omtrent 25000 enzym-enheter pr. g polymer (1 enhet 1 mmol hydrolysert penicillin G pr. time ved 37°C).. Phenicillin acyiase was extracted and purified from Sscherichia Coli,. the strain of ATCC 9637, and enclosed in cellulose triacetate fibers according to the method described in Italian patent document 836,462 so that fibers containing approximately 25,000 enzyme units per g polymer (1 unit of 1 mmol hydrolyzed penicillin G per hour at 37°C)..
5D0 mg (2.33 mmol) 7-amino, 3-metyl,cef-3-em-4-karboksylsyre (7 \DCA) og 1 g (4.97 mmol) D(-) fenyl-glycinmetylesterlsloro-hycxat (PG24) ble opplost i 50 ral av en 0.1 M kaliumfosfat-buffer ved pH 7.00 ved 25°C. Denne oppløsning ble under omrøring holdt i kontakt med 2 g fiber tilsvarende 1 g cellulosetriacetat (CTA) inneholdt i et glas sr or forsynt med kappe.. Ved regelmessige tidsmellomrom ble 7 ø (2 '-araino-2 '-fenylacetamid-).,3-.metyl-3ef-3-emr4-karboksylsyre (cefalxin) bestemt ved hjelp av ett s pek tro-fotometrisk metode (AKALYST, 92, 247, 1967). Etter 1 time bi^reaksjonen stanset ved å fjerne réaksjonsblåndingen fra fiberene. I oppløsningen var det B, A mg/ml cefalxin tilsvarende en omdannelse av 7 M)C& på 51%. 5D0 mg (2.33 mmol) 7-amino, 3-methyl, cef-3-em-4-carboxylic acid (7\DCA) and 1 g (4.97 mmol) D(-) phenyl-glycine methyl ester chlorohycxate (PG24) were dissolved in 50 ral of a 0.1 M potassium phosphate buffer at pH 7.00 at 25°C. This solution, while stirring, was kept in contact with 2 g of fiber corresponding to 1 g of cellulose triacetate (CTA) contained in a glass sr or provided with a jacket. At regular intervals, 7 ø (2 '-araino-2 '-phenylacetamide-)., 3-.Methyl-3ef-3-emr4-carboxylic acid (cefalxin) determined by means of a spectrophotometric method (AKALYST, 92, 247, 1967). After 1 hour, the reaction was stopped by removing the reaction mixture from the fibers. In the solution there was B, A mg/ml cefalxin corresponding to a conversion of 7 M)C& of 51%.
Eksempel 2.Example 2.
Det ble fremstilt en løsning aV 7-ADCA og .PGM som beskrevet i eksempel 1 men pH var 6.50. A solution containing 7-ADCA and .PGM was prepared as described in example 1, but the pH was 6.50.
BSter omtrent 2 timer ble reaksjonen avbrutt som nevnt ovenfor.. I løsningen var det 8.1 mg/ml cefalxin tilsvarende 495$ omdannelse. After approximately 2 hours the reaction was interrupted as mentioned above. In the solution there was 8.1 mg/ml cefalxin corresponding to 495$ conversion.
Eksempel 3.Example 3.
Det ble fremstilt en løsning av 7-ADCA og PGM i henhold til eksempel 1 men pH var lik 8.50. A solution of 7-ADCA and PGM was prepared according to example 1 but the pH was equal to 8.50.
Etter omtrent 30 minutter ble reaksjonen avbrutt og i løsningen var det 7.8 mg/ml cefalxin tilsvarende en 47% omdannelse. After approximately 30 minutes, the reaction was interrupted and the solution contained 7.8 mg/ml cefalxin corresponding to a 47% conversion.
Eksempel 4.Example 4.
500 mg (2.33 mmol) 7 ADCA og 2 g (9.94 mmol) PGM ble oppløst i 50 ml K-PO^buffer 0,2 M ved pH 7. Denne oppløsning som ved h-^glp 500 mg (2.33 mmol) 7 ADCA and 2 g (9.94 mmol) PGM were dissolved in 50 ml K-PO^buffer 0.2 M at pH 7. This solution as in h-^glp
av termostat ble boldt véd^25?G ble.under, ^omrdriisg^holdt--1* kontakt med 2 g fiber il time. atter denne tid var det i løsningen 12 mg/ml.cefalxin tilsvarende 73% omdannelse av 7 ADCA. of thermostat was boldt véd^25?G was.under, ^omrdriisg^kept--1* contact with 2 g fiber 1 hour. again this time there was 12 mg/ml cefalxin in the solution corresponding to 73% conversion of 7 ADCA.
Eksempel 5.Example 5.
En løsning ble fremstilt i henhold til eksempel 4 og under omrøring br agt i kontakt med 2 g fiber som ved hjelp av termostat ble holdt ved 37°C. Reaksjonen ble avbrutt etter 30 minutter. A solution was prepared according to example 4 and, while stirring, brought into contact with 2 g of fiber which was kept at 37°C by means of a thermostat. The reaction was stopped after 30 minutes.
I oppløsningen var det 11.4 mg/ml cefalxin tilsvarende en 70% In the solution there was 11.4 mg/ml cefalxin corresponding to a 70%
omdannelse.conversion.
Eksempel 6.Example 6.
500 mg (2.31 mmol) 6-aminopenicillansyre (6-APA) og 2 g (10.2 mmol) etyleater av D(-) p-hydroksyifenyl-glycin (p-OH PGE) ble oppløst 1150 ml "~P04buffer 0.1 M ved pH 7.00 ved 25°C. Oppløsningen ble under omrøring holdt i kontakt med 2 g fiber 500 mg (2.31 mmol) 6-aminopenicillanic acid (6-APA) and 2 g (10.2 mmol) ethylates of D(-) p-hydroxyiphenyl-glycine (p-OH PGE) were dissolved in 1150 ml "~PO4buffer 0.1 M at pH 7.00 at 25° C. The solution was kept in contact with 2 g of fiber while stirring
i 3 timer og deretter fjernet.for 3 hours and then removed.
It/oppløsningen var Set 1.7 mg/ml e-araino-p-hydroksy-banzyl-penicillin (amoksycillin) tilsvarende en 6-APA omdannelse på 30?L It/solution was Set 1.7 mg/ml e-araino-p-hydroxy-banzyl-penicillin (amoxycillin) corresponding to a 6-APA conversion of 30?L
STcsempel 7.Example 7.
4 g 6-APA (18.7 mmol) og 2 g (10.2 mmol) pOIi-PGE ble oppløst4 g 6-APA (18.7 mmol) and 2 g (10.2 mmol) pOIi-PGE were dissolved
i 150 ml K-P04buffer 0.1 11 ved pH 7.00 og 25°C og ble under omrøring holdt i kontakt med 4 g fiber.. Reaksjonen ble avbrutt etter 7 timer og da var konsentrasjonen av amoksycillin 7.2 mg/ml tilsvarende 15.7% omdannelse. in 150 ml of K-PO4 buffer 0.1 11 at pH 7.00 and 25°C and was kept in contact with 4 g of fiber while stirring. The reaction was interrupted after 7 hours and then the concentration of amoxicillin was 7.2 mg/ml corresponding to 15.7% conversion.
Eksempel 8.Example 8.
500 mg (2.33 raapl) 7ADCA og 1 g (5.1 mmol) pOH PGE ble opplost i 150 ml K-PO^buffer 0.1 £4 ved pH 7.00 ved 25°C. Etter 4 timer ble reaksjonen avbrutt som tidligere nevnt. 500 mg (2.33 raapl) 7ADCA and 1 g (5.1 mmol) pOH PGE were dissolved in 150 ml K-PO^buffer 0.1 £4 at pH 7.00 at 25°C. After 4 hours the reaction was stopped as previously mentioned.
I reaksjonsblandingen var det 2 mg/ml 7|3^2'arainc—2M~4vhydr.okBy~ fenyl) acetamid73 metyl, cef-3-era-4-karboksylsyre tii svarende en 35.4% omdaimelae. In the reaction mixture there was 2 mg/ml 7|3^2'arainc—2M~4vhydr.okBy~phenyl)acetamide73 methyl, cef-3-era-4-carboxylic acid tii corresponding to a 35.4% omdaimelae.
Eksempel 9. • Example 9. •
535 mg (2.5 mmol) 7 ADCA og 873 mg (2.5 mmol) a-aminobenzyl penicillin (aapicillin) ble opplost i 50 ml IC-PO^, buffer 0.1 M 535 mg (2.5 mmol) 7 ADCA and 873 mg (2.5 mmol) α-aminobenzyl penicillin (aapicillin) were dissolved in 50 ml IC-PO^, buffer 0.1 M
ved pH 7.00 ved 25°C*Oppløsningen ble holdt i kontakt med 1 g fiber under omrøring. at pH 7.00 at 25°C* The solution was kept in contact with 1 g of fiber while stirring.
Stter Nitime ble det oppnådd maksimal konsentrasjon av cefalxin tilsvarende 3.5 mg/ral tilsvarende en 20% omdannelse av 7 ADCA. Stter Nitime, the maximum concentration of cefalxin corresponding to 3.5 mg/ral corresponding to a 20% conversion of 7 ADCA was achieved.
Eksempel 10.Example 10.
500 mg (2.33 mmol) 7ADCAog 1.35 g (9 mmol) fenylglycinaciid ble opplost i 50 nu/K-P04buffer 0.1 ti ved pH 7. Oppløsningen ble under omrøring holdt i kontakt med 2 g fiber i omtrent 1 500 mg (2.33 mmol) 7ADCA and 1.35 g (9 mmol) phenylglycinacid were dissolved in 50 nu/K-PO4 buffer 0.1 ti at pH 7. The solution was kept in contact with 2 g of fiber for about 1
time ved 25°C. Etter dette tidsrom var det i løsningen 11 mg/ral cefalxin tilsvarende 68% omdannelse av 7 ADCA. hour at 25°C. After this period, there was 11 mg/ral cefalxin in the solution corresponding to 68% conversion of 7 ADCA.
Eksempel 11.Example 11.
640 rag (2.35 mmol) 7-aminocefalosporansyre (7-ADCA) og 1.0 g (5.1 mmol) p-hydroksyfenylglicinetylester ble oppløst i 15© ml 640 mg (2.35 mmol) 7-aminocephalosporanic acid (7-ADCA) and 1.0 g (5.1 mmol) p-hydroxyphenylglycine ethyl ester were dissolved in 15 ml
fosfatbuffer 0.1 M ved pH 7 ved 25°C. / phosphate buffer 0.1 M at pH 7 at 25°C. /
Oppløsningen bie under omrøring holdt i kontakt med 2 g enzymholdig fiber i 4 timer. Btter dette tidsrom var det i reaksjonsblac&ingen 1.9 mg/mi. 73 (2,-amino-2,-(4-hydroksyfenyl) aceta^id) 3-hydroksy-metyl (acetat) cef-3-em-4-karboksylsyre tilsvarende efc. ut'?ytte på-29%. ved omdannelsen av 7 ADCA. The solution bee under stirring kept in contact with 2 g of enzyme-containing fiber for 4 hours. After this period, there was 1.9 mg/mi in the reaction blank. 73 (2,-amino-2,-(4-hydroxyphenyl)aceta^ide)3-hydroxy-methyl (acetate)cef-3-em-4-carboxylic acid corresponding to efc. yield of -29%. in the conversion of 7 ADCA.
Claims (7)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT54486/73A IT1045797B (en) | 1973-12-20 | 1973-12-20 | SEMI-SYNTHETIC PENICILLIN AND CEPHALOSPORINE SYNTHESIS PROCEDURE BY MEANS OF AN INSOLUBLE ACYLASE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO744591L true NO744591L (en) | 1975-07-14 |
Family
ID=11287339
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO744591A NO744591L (en) | 1973-12-20 | 1974-12-19 |
Country Status (20)
| Country | Link |
|---|---|
| JP (1) | JPS5095487A (en) |
| AU (1) | AU7593874A (en) |
| BE (1) | BE823393A (en) |
| CH (1) | CH606432A5 (en) |
| CS (1) | CS190459B2 (en) |
| DD (1) | DD115683A5 (en) |
| DE (1) | DE2460649A1 (en) |
| DK (1) | DK661074A (en) |
| FI (1) | FI362174A (en) |
| FR (1) | FR2255379B1 (en) |
| GB (1) | GB1482481A (en) |
| HU (1) | HU172712B (en) |
| IL (1) | IL46151A0 (en) |
| IT (1) | IT1045797B (en) |
| LU (1) | LU71482A1 (en) |
| NL (1) | NL7416548A (en) |
| NO (1) | NO744591L (en) |
| SE (1) | SE7416078L (en) |
| YU (1) | YU335574A (en) |
| ZA (1) | ZA747896B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1243800B (en) * | 1990-08-28 | 1994-06-28 | Sclavo Spa | IMPROVED PROCEDURE FOR THE PREPARATION OF CEPHALOSPORINE |
| NZ247464A (en) * | 1992-04-24 | 1994-12-22 | Lilly Co Eli | Preparation of 2-amino-acetamidocephalosporin derivatives, the 2-acetamido group substituted in the 2-position by a c5-6 cyclic hydrocarbon or a c5-heterocycle |
| IT1274658B (en) * | 1995-02-28 | 1997-07-18 | Acs Dobfar Spa | IMPROVED ENZYMATIC PROCEDURE FOR THE PRODUCTION OF PENICILLINS AND CEPHALOSPORINS |
-
1973
- 1973-12-20 IT IT54486/73A patent/IT1045797B/en active
-
1974
- 1974-11-28 IL IL46151A patent/IL46151A0/en unknown
- 1974-12-02 AU AU75938/74A patent/AU7593874A/en not_active Expired
- 1974-12-05 FR FR7439837A patent/FR2255379B1/fr not_active Expired
- 1974-12-10 CH CH1640174A patent/CH606432A5/xx not_active IP Right Cessation
- 1974-12-11 ZA ZA00747896A patent/ZA747896B/en unknown
- 1974-12-13 LU LU71482A patent/LU71482A1/xx unknown
- 1974-12-16 FI FI3621/74A patent/FI362174A/fi unknown
- 1974-12-16 GB GB54337/74A patent/GB1482481A/en not_active Expired
- 1974-12-16 BE BE151539A patent/BE823393A/en not_active IP Right Cessation
- 1974-12-17 YU YU03355/74A patent/YU335574A/en unknown
- 1974-12-18 NL NL7416548A patent/NL7416548A/en unknown
- 1974-12-18 DK DK661074A patent/DK661074A/da unknown
- 1974-12-19 SE SE7416078A patent/SE7416078L/xx unknown
- 1974-12-19 HU HU74SA00002732A patent/HU172712B/en unknown
- 1974-12-19 NO NO744591A patent/NO744591L/no unknown
- 1974-12-20 CS CS748820A patent/CS190459B2/en unknown
- 1974-12-20 JP JP49145851A patent/JPS5095487A/ja active Pending
- 1974-12-20 DE DE19742460649 patent/DE2460649A1/en active Pending
- 1974-12-20 DD DD183278A patent/DD115683A5/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5095487A (en) | 1975-07-29 |
| BE823393A (en) | 1975-04-16 |
| YU335574A (en) | 1982-05-31 |
| CS190459B2 (en) | 1979-05-31 |
| IL46151A0 (en) | 1975-02-10 |
| IT1045797B (en) | 1980-06-10 |
| NL7416548A (en) | 1975-06-24 |
| HU172712B (en) | 1978-11-28 |
| FI362174A (en) | 1975-06-21 |
| LU71482A1 (en) | 1975-06-17 |
| SE7416078L (en) | 1975-06-23 |
| FR2255379B1 (en) | 1977-10-28 |
| ZA747896B (en) | 1975-12-31 |
| DK661074A (en) | 1975-08-25 |
| DD115683A5 (en) | 1975-10-12 |
| CH606432A5 (en) | 1978-10-31 |
| FR2255379A1 (en) | 1975-07-18 |
| DE2460649A1 (en) | 1975-06-26 |
| GB1482481A (en) | 1977-08-10 |
| AU7593874A (en) | 1976-06-03 |
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