HRP20180435T1 - Postupak za pripremu cefradina - Google Patents
Postupak za pripremu cefradina Download PDFInfo
- Publication number
- HRP20180435T1 HRP20180435T1 HRP20180435TT HRP20180435T HRP20180435T1 HR P20180435 T1 HRP20180435 T1 HR P20180435T1 HR P20180435T T HRP20180435T T HR P20180435TT HR P20180435 T HRP20180435 T HR P20180435T HR P20180435 T1 HRP20180435 T1 HR P20180435T1
- Authority
- HR
- Croatia
- Prior art keywords
- cephradine
- reaction
- dihydrophenylglycine
- reaction mixture
- adca
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 21
- RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 title claims 16
- 229960002588 cefradine Drugs 0.000 title claims 13
- 238000002360 preparation method Methods 0.000 title claims 2
- 238000006243 chemical reaction Methods 0.000 claims 13
- 239000011541 reaction mixture Substances 0.000 claims 9
- 239000007864 aqueous solution Substances 0.000 claims 7
- 108090000790 Enzymes Proteins 0.000 claims 6
- 102000004190 Enzymes Human genes 0.000 claims 6
- 238000002425 crystallisation Methods 0.000 claims 4
- 230000008025 crystallization Effects 0.000 claims 4
- 150000004702 methyl esters Chemical class 0.000 claims 2
- 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 claims 1
- 108010073038 Penicillin Amidase Proteins 0.000 claims 1
- 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 claims 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- CSGFFYNMTALICU-ZWNOBZJWSA-N adipyl-7-aminodesacetoxycephalosporanic acid Natural products CC1=C(N2[C@H](SC1)[C@H](NC(=O)CCCCC(O)=O)C2=O)C(O)=O CSGFFYNMTALICU-ZWNOBZJWSA-N 0.000 claims 1
- 238000004090 dissolution Methods 0.000 claims 1
- 150000003840 hydrochlorides Chemical class 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
Claims (15)
1. Postupak za pripremanje cefradina, te navedeni postupak sadrži reakciju 7- aminodeacetoksi cefalosporanske kiseline (7-ADCA) s D-dihidrofenilglicinom u aktiviranom obliku (DHa) u prisutnosti enzima u reakcijskoj smjesi da nastane cefradin, što dovodi do pretvaranja 7-ADCA u cefradin od barem 70 %, pri čemu se koncentracija D-dihidrofenilglicina (DH) u reakcijskoj smjesi održava ispod 2 mas.% tijekom reakcije pri čemu navedeni enzim je divlji tip penicilin acilaze, i pri čemu se navedena reakcija provodi na temperaturi ispod 15°C i kod pH od barem 7.0 ili pri čemu navedeni enzim je Pen-G acilaza mutant Phe-24-Ala, te pri čemu se navedena reakcija provodi na temperaturi od barem 15°C i kod pH ispod 7.7.
2. Postupak prema zahtjevu 1, naznačen time da navedena reakcija dovodi do pretvaranja 7-ADCA u cefradin od barem 80%.
3. Postupak prema zahtjevu 1 ili 2, naznačen time da navedena reakcija dovodi do pretvaranja D-dihidrofenilglicina u aktiviranom obliku (DHa) u cefradin (CEF) od barem 70%, pri čemu pretvaranje DHa u CEF = (nCEF / nDHa)*100%; NCEF = količina nastalog cefradina (u mol); i nDHa = ukupna količina DHa dodana u reakcijsku smjesu (u mol).
4. Postupak prema bilo kojem od zahtjeva 1 do 3, naznačen time da je zbroj količine 7-ADCA dodane u reakcijsku smjesu i DHa dodanog u reakcijsku smjesu između 10 i 2000 mmol po litri reakcijske smjese.
5. Postupak prema bilo kojem od zahtjeva 1 do 4, naznačen time da D-dihidrofenilglicin u aktiviranom obliku je D-dihidrofenilglicin metilnog estera.
6. Postupak prema bilo kojem od zahtjeva 1 do 5, naznačen time da D- dihidrofenilglicin u aktiviranom obliku je HCl soli D-dihidrofenilglicin metilnog estera.
7. Postupak prema bilo kojem od zahtjeva 1 do 6, naznačen time da je enzim imobiliziran na nosaču.
8. Postupak prema bilo kojem od zahtjeva 1 do 7, naznačen time da postupak obuhvaća kristalizaciju cefradina iz vodene otopine.
9. Postupak prema zahtjevu 8, naznačen time da navedeni postupak sadrži reakciju 7-aminodeacetoksi cefalosporanske kiseline (7-ADCA) s D-dihidrofenilglicinom u aktiviranom obliku (DHa) u prisutnosti enzima u reakcijskoj smjesi da nastane cefradin i kristaliziranje cefradina iz vodene otopine, u kojoj je omjer vodene otopine mCEF/(m7-ADCA + mCEF) > 0.7 i pri čemu xDH = 0-2 mas.%, pri čemu mCEF = molarna količina cefradina u vodenoj otopini; m7-ADCA = molarna količina 7-ADCA u vodenoj otopini; i xDH = koncentracija DH u vodenoj otopini u odnosu na ukupnu masu vodene otopine.
10. Postupak prema zahtjevu 8 ili zahtjevu 9, naznačen time da postupak obuhvaća odvajanje enzima iz cefradina prije navedene kristalizacije.
11. Postupak prema bilo kojem od zahtjeva 8 do 10, naznačen time da se navedena kristalizacija provodi kod pH od između 4.0 i 6.0.
12. Postupak prema bilo kojem od zahtjeva 1 do 11, naznačen time da je dio nastalog cefradina prisutan u reakcijskoj smjesi kao cefradin hidrat, te pri čemu postupak obuhvaća otapanje barem dijela navedenog cefradin hidrata.
13. Postupak prema zahtjevu 12, naznačen time da se navedeno otapanje provodi kod pH od iznad 8.
14. Postupak prema bilo kojem od zahtjeva 1 do 13 naznačen time da se navedena reakcija provodi u prisutnosti natrijevog bisulfita.
15. Postupak prema bilo kojem od prethodnih zahtjeva, naznačen time da se koncentracija D-dihidrofenilglicina u reakcijskoj smjesi održava ispod 1 mas.% tijekom reakcije.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03077102 | 2003-07-03 | ||
| EP03104445 | 2003-11-28 | ||
| PCT/EP2004/007291 WO2005003367A2 (en) | 2003-07-03 | 2004-07-01 | Process for the preparation of cephradine |
| EP04740631.9A EP1641933B1 (en) | 2003-07-03 | 2004-07-01 | Process for the preparation of cephradine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20180435T1 true HRP20180435T1 (hr) | 2018-04-20 |
Family
ID=33566322
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20180435TT HRP20180435T1 (hr) | 2003-07-03 | 2018-03-14 | Postupak za pripremu cefradina |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7588913B2 (hr) |
| EP (1) | EP1641933B1 (hr) |
| BR (1) | BRPI0412302A (hr) |
| DK (1) | DK1641933T3 (hr) |
| HR (1) | HRP20180435T1 (hr) |
| HU (1) | HUE036242T2 (hr) |
| LT (1) | LT1641933T (hr) |
| SI (1) | SI1641933T1 (hr) |
| WO (1) | WO2005003367A2 (hr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI2367940T1 (en) * | 2008-12-23 | 2018-04-30 | Dsm Sinochem Pharmaceuticals Netherlands B.V. | Mutated penicillin G acylase |
| CN102656274B (zh) | 2009-12-14 | 2014-10-15 | 中化帝斯曼制药有限公司荷兰公司 | 生产头孢拉定的方法 |
| CN103667418B (zh) * | 2013-12-18 | 2015-03-25 | 华北制药河北华民药业有限责任公司 | 高活性β-内酰胺抗生素合成用酶的高通量筛选方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3485819A (en) | 1968-07-02 | 1969-12-23 | Squibb & Sons Inc | Alpha-amino-cyclohexadienylalkylene-penicillins and cephalosporins |
| US3819620A (en) * | 1972-06-01 | 1974-06-25 | Squibb & Sons Inc | 7-(d-alpha-amino-1,4-cyclohexadien-1-ylacet-amido)desacetoxycephalosporanic acid dihydrate |
| JPS51133488A (en) | 1975-05-14 | 1976-11-19 | Shionogi & Co Ltd | Process for producing antibiotics enzymatically |
| IT1065387B (it) * | 1976-12-16 | 1985-02-25 | Dobfar Spa | Proccedimento per la preparazione di cefalosporine |
| US5034522A (en) | 1988-08-02 | 1991-07-23 | Biocraft Laboratories, Inc. | Method for the production of 3-methyl cephem derivatives |
| US5278157A (en) * | 1989-07-10 | 1994-01-11 | Gema, S.A. | Stable cephradine hydrate |
| ES2023560A6 (es) | 1989-07-10 | 1992-01-16 | Gema Sa | Procedimiento para la produccion de hidrato de cefradina y solvato de cefradina y dimetilformamida. |
| ES2139923T3 (es) * | 1994-07-18 | 2000-02-16 | Dsm Nv | Procedimiento para preparar beta-lactamas a concentraciones de reaccionantes constantemente altas. |
| ATE417100T1 (de) * | 1995-07-18 | 2008-12-15 | Dsm Ip Assets Bv | Eine verbesserte immobilisierte penicillin g acylase |
| AU8021398A (en) | 1997-06-10 | 1998-12-30 | Gist-Brocades B.V. | Application of reducing sulphur compounds during enzymatic preparation of beta-lactam compounds |
| AU1234999A (en) * | 1997-11-10 | 1999-05-31 | Gist-Brocades B.V. | Crystallization of beta-lactam compounds |
| NL1007828C2 (nl) | 1997-12-18 | 1999-06-21 | Dsm Nv | Complexen van beta-lactam antibiotica en 1-naftol. |
| EP0997199A1 (en) | 1998-10-26 | 2000-05-03 | Dsm N.V. | Method for separation of solid compounds in suspension |
| EP1456370A2 (en) * | 2001-12-27 | 2004-09-15 | DSM IP Assets B.V. | Process for the preparation of a beta-lactam antibiotic with mutated penicillin acylase |
| EP1458727B1 (en) | 2001-12-27 | 2005-08-31 | DSM IP Assets B.V. | Process for the stabilization of an acidic aqueous phase comprising cephradine |
-
2004
- 2004-07-01 WO PCT/EP2004/007291 patent/WO2005003367A2/en active Application Filing
- 2004-07-01 US US10/562,345 patent/US7588913B2/en active Active
- 2004-07-01 BR BRPI0412302-6A patent/BRPI0412302A/pt not_active IP Right Cessation
- 2004-07-01 EP EP04740631.9A patent/EP1641933B1/en active Active
- 2004-07-01 HU HUE04740631A patent/HUE036242T2/hu unknown
- 2004-07-01 DK DK04740631.9T patent/DK1641933T3/en active
- 2004-07-01 SI SI200432433T patent/SI1641933T1/en unknown
- 2004-07-01 LT LTEP04740631.9T patent/LT1641933T/lt unknown
-
2018
- 2018-03-14 HR HRP20180435TT patent/HRP20180435T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK1641933T3 (en) | 2018-03-26 |
| HUE036242T2 (hu) | 2018-06-28 |
| EP1641933A2 (en) | 2006-04-05 |
| WO2005003367A3 (en) | 2005-05-26 |
| SI1641933T1 (en) | 2018-04-30 |
| US20060189802A1 (en) | 2006-08-24 |
| US7588913B2 (en) | 2009-09-15 |
| EP1641933B1 (en) | 2017-12-20 |
| WO2005003367A2 (en) | 2005-01-13 |
| LT1641933T (lt) | 2018-04-10 |
| BRPI0412302A (pt) | 2006-06-13 |
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