CH638521A5 - Process for obtaining the antibiotic thienamycin - Google Patents

Process for obtaining the antibiotic thienamycin Download PDF

Info

Publication number: CH638521A5
Authority: CH; Switzerland
Prior art keywords: liquid; antibiotic; solvent; exchangers; thienamycin
Prior art date: 1977-03-01

Application number

CH204578A

Other languages

German (de)

English (en)

Inventor

Rathin Datta

George Thomas Wildman

Original Assignee

Merck & Co Inc

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.)

1977-03-01

Filing date

1978-02-24

Publication date

1983-09-30

1978-02-24 Application filed by Merck & Co Inc filed Critical Merck & Co Inc

1983-09-30 Publication of CH638521A5 publication Critical patent/CH638521A5/de

Links

WKDDRNSBRWANNC-ATRFCDNQSA-N Thienamycin Chemical compound C1C(SCCN)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 WKDDRNSBRWANNC-ATRFCDNQSA-N 0.000 title claims description 37
WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 title claims description 37
238000000034 method Methods 0.000 title claims description 26
230000003115 biocidal effect Effects 0.000 title claims description 25
239000007788 liquid Substances 0.000 claims description 53
239000002904 solvent Substances 0.000 claims description 21
150000001450 anions Chemical class 0.000 claims description 19
235000010633 broth Nutrition 0.000 claims description 17
150000001768 cations Chemical class 0.000 claims description 14
150000002500 ions Chemical class 0.000 claims description 14
238000000605 extraction Methods 0.000 claims description 13
238000005342 ion exchange Methods 0.000 claims description 13
239000012062 aqueous buffer Substances 0.000 claims description 12
238000000855 fermentation Methods 0.000 claims description 11
230000004151 fermentation Effects 0.000 claims description 11
239000003960 organic solvent Substances 0.000 claims description 10
CJMZLCRLBNZJQR-UHFFFAOYSA-N ethyl 2-amino-4-(4-fluorophenyl)thiophene-3-carboxylate Chemical compound CCOC(=O)C1=C(N)SC=C1C1=CC=C(F)C=C1 CJMZLCRLBNZJQR-UHFFFAOYSA-N 0.000 claims description 9
238000005341 cation exchange Methods 0.000 claims description 7
150000003839 salts Chemical class 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 6
ZUZLIXGTXQBUDC-UHFFFAOYSA-N methyltrioctylammonium Chemical compound CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC ZUZLIXGTXQBUDC-UHFFFAOYSA-N 0.000 claims description 4
150000001298 alcohols Chemical class 0.000 claims description 3
150000002148 esters Chemical class 0.000 claims description 3
150000002576 ketones Chemical class 0.000 claims description 3
230000000694 effects Effects 0.000 claims description 2
NFWZTFWARDHQBM-UHFFFAOYSA-M methyl-tri(octanoyl)azanium;acetate Chemical compound CC([O-])=O.CCCCCCCC(=O)[N+](C)(C(=O)CCCCCCC)C(=O)CCCCCCC NFWZTFWARDHQBM-UHFFFAOYSA-M 0.000 claims description 2
239000004254 Ammonium phosphate Substances 0.000 claims 1
229910000148 ammonium phosphate Inorganic materials 0.000 claims 1
235000019289 ammonium phosphates Nutrition 0.000 claims 1
229910052921 ammonium sulfate Inorganic materials 0.000 claims 1
239000012071 phase Substances 0.000 description 16
239000000243 solution Substances 0.000 description 12
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
239000008346 aqueous phase Substances 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
239000002609 medium Substances 0.000 description 7
239000011347 resin Substances 0.000 description 7
229920005989 resin Polymers 0.000 description 7
239000012074 organic phase Substances 0.000 description 6
238000005349 anion exchange Methods 0.000 description 5
239000000203 mixture Substances 0.000 description 5
229920001467 poly(styrenesulfonates) Polymers 0.000 description 5
238000000926 separation method Methods 0.000 description 5
239000011734 sodium Substances 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
229920001429 chelating resin Polymers 0.000 description 4
239000000499 gel Substances 0.000 description 4
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
239000007787 solid Substances 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
239000003463 adsorbent Substances 0.000 description 3
239000003242 anti bacterial agent Substances 0.000 description 3
229940088710 antibiotic agent Drugs 0.000 description 3
239000000872 buffer Substances 0.000 description 3
125000002091 cationic group Chemical group 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
150000001875 compounds Chemical class 0.000 description 3
238000011033 desalting Methods 0.000 description 3
239000001963 growth medium Substances 0.000 description 3
XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 3
244000005700 microbiome Species 0.000 description 3
229910001220 stainless steel Inorganic materials 0.000 description 3
239000010935 stainless steel Substances 0.000 description 3
230000001954 sterilising effect Effects 0.000 description 3
238000004659 sterilization and disinfection Methods 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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 2
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
241001147855 Streptomyces cattleya Species 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000003957 anion exchange resin Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
239000008367 deionised water Substances 0.000 description 2
229910021641 deionized water Inorganic materials 0.000 description 2
230000007717 exclusion Effects 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000005227 gel permeation chromatography Methods 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
238000002955 isolation Methods 0.000 description 2
239000007791 liquid phase Substances 0.000 description 2
239000012046 mixed solvent Substances 0.000 description 2
239000003791 organic solvent mixture Substances 0.000 description 2
238000005192 partition Methods 0.000 description 2
238000005191 phase separation Methods 0.000 description 2
229920002401 polyacrylamide Polymers 0.000 description 2
229920000151 polyglycol Polymers 0.000 description 2
239000010695 polyglycol Substances 0.000 description 2
235000011056 potassium acetate Nutrition 0.000 description 2
238000000746 purification Methods 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011877 solvent mixture Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
IILMIAKZFKOMTK-UHFFFAOYSA-N 2,3-didodecylnaphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(O)(=O)=O)=C(CCCCCCCCCCCC)C(CCCCCCCCCCCC)=CC2=C1 IILMIAKZFKOMTK-UHFFFAOYSA-N 0.000 description 1
BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
102000011045 Chloride Channels Human genes 0.000 description 1
108010062745 Chloride Channels Proteins 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
239000007836 KH2PO4 Substances 0.000 description 1
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 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 description 1
241000364057 Peoria Species 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
241000187747 Streptomyces Species 0.000 description 1
241001531149 Streptomyces cattleya NRRL 8057 = DSM 46488 Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
239000002250 absorbent Substances 0.000 description 1
230000002745 absorbent Effects 0.000 description 1
239000008351 acetate buffer Substances 0.000 description 1
SJJRZWOJZJDKCO-UHFFFAOYSA-N acetic acid;2,6-dimethylpyridine Chemical compound CC(O)=O.CC1=CC=CC(C)=N1 SJJRZWOJZJDKCO-UHFFFAOYSA-N 0.000 description 1
230000002411 adverse Effects 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000003729 cation exchange resin Substances 0.000 description 1
-1 cationic ion Chemical class 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
SEGLCEQVOFDUPX-UHFFFAOYSA-N di-(2-ethylhexyl)phosphoric acid Chemical compound CCCCC(CC)COP(O)(=O)OCC(CC)CCCC SEGLCEQVOFDUPX-UHFFFAOYSA-N 0.000 description 1
229940061607 dibasic sodium phosphate Drugs 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
229910000397 disodium phosphate Inorganic materials 0.000 description 1
239000011536 extraction buffer Substances 0.000 description 1
229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
238000012827 research and development Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
235000011008 sodium phosphates Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
239000012607 strong cation exchange resin Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/02—Preparation
- 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
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
- C12P17/182—Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system
- C12P17/184—Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system containing a beta-lactam ring, e.g. thienamycin

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Wood Science & Technology (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Zoology (AREA)
Biochemistry (AREA)
General Engineering & Computer Science (AREA)
Microbiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Biotechnology (AREA)
Molecular Biology (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Saccharide Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CH204578A 1977-03-01 1978-02-24 Process for obtaining the antibiotic thienamycin CH638521A5 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US77335477A	1977-03-01	1977-03-01

Publications (1)

Publication Number	Publication Date
CH638521A5 true CH638521A5 (en)	1983-09-30

Family

ID=25097982

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH204578A CH638521A5 (en)	1977-03-01	1978-02-24	Process for obtaining the antibiotic thienamycin

Country Status (11)

Country	Link
JP (1)	JPS53107483A (pt)
CH (1)	CH638521A5 (pt)
DE (1)	DE2808636A1 (pt)
DK (1)	DK144097C (pt)
ES (1)	ES467309A1 (pt)
FR (1)	FR2382453A1 (pt)
GB (1)	GB1568924A (pt)
IT (1)	IT1103481B (pt)
NL (1)	NL7801756A (pt)
PT (1)	PT67721A (pt)
SE (1)	SE7801695L (pt)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0024447B1 (en) *	1979-08-28	1983-07-20	Merck & Co. Inc.	Process for purifying thienamycin
DE3146190A1 (de) *	1981-11-21	1983-06-16	Hoechst Ag, 6230 Frankfurt	Isolierung von chemisch instabilen antibiotika aus fermentationsloesungen

1978
- 1978-02-14 SE SE7801695A patent/SE7801695L/xx unknown
- 1978-02-15 DK DK67478A patent/DK144097C/da not_active IP Right Cessation
- 1978-02-16 NL NL7801756A patent/NL7801756A/xx not_active Application Discontinuation
- 1978-02-24 CH CH204578A patent/CH638521A5/de not_active IP Right Cessation
- 1978-02-24 ES ES467309A patent/ES467309A1/es not_active Expired
- 1978-02-24 IT IT48188/78A patent/IT1103481B/it active
- 1978-02-27 GB GB7719/78A patent/GB1568924A/en not_active Expired
- 1978-02-27 FR FR7805531A patent/FR2382453A1/fr active Granted
- 1978-02-28 DE DE19782808636 patent/DE2808636A1/de not_active Withdrawn
- 1978-03-01 JP JP2215478A patent/JPS53107483A/ja active Pending
- 1978-03-01 PT PT67721A patent/PT67721A/pt unknown

Also Published As

Publication number	Publication date
JPS53107483A (en)	1978-09-19
DK144097C (da)	1982-05-17
IT1103481B (it)	1985-10-14
NL7801756A (nl)	1978-09-05
IT7848188A0 (it)	1978-02-24
DK144097B (da)	1981-12-07
ES467309A1 (es)	1979-08-16
SE7801695L (sv)	1978-09-02
FR2382453A1 (fr)	1978-09-29
GB1568924A (en)	1980-06-11
PT67721A (en)	1978-04-01
DE2808636A1 (de)	1978-09-07
DK67478A (da)	1978-09-02
FR2382453B1 (pt)	1982-11-19

Legal Events

Date	Code	Title	Description
1984-10-31	PL	Patent ceased
2024-10-31	PL	Patent ceased

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DE69315234T2 (de)	1998-05-20	Verfahren zur Herstellung von Alpha-Glykosyl- L-Ascorbinsäure mit hohem Produktanteil
DE69500925T2 (de)	1998-02-12	Verfahren zur isolation von clavulansäure und von pharmazeutisch verträgliche salze aus fermentationsbrühe von streptomyces sp.p6621 ferm p2804
DE69216297T2 (de)	1997-06-05	Verfahren zur Herstellung von gereinigte Milchsäure enthaltenden wässrigen Lösungen aus Fermentationsbrühen
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US2658078A (en)	1953-11-03	Solvent extraction of oxytetracycline
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