CA1107739A - COMPOSES DE TYPE .beta.-LACTAME - Google Patents

COMPOSES DE TYPE .beta.-LACTAME

Info

Publication number: CA1107739A
Authority: CA; Canada
Prior art keywords: compound; formula; ester; group; preparation
Prior art date: 1977-08-04
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

CA308,302A

Other languages

English (en)

Inventor

Brian C. Gasson

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.)

Beecham Group PLC

Original Assignee

Beecham Group PLC

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.)

1977-08-04

Filing date

1978-07-27

Publication date

1981-08-25

1978-07-27 Application filed by Beecham Group PLC filed Critical Beecham Group PLC

1981-01-16 Priority to CA000368746A priority Critical patent/CA1121360A/fr

1981-08-25 Application granted granted Critical

1981-08-25 Publication of CA1107739A publication Critical patent/CA1107739A/fr

Status Expired legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 claims abstract description 57
150000002148 esters Chemical class 0.000 claims abstract description 38
238000000034 method Methods 0.000 claims abstract description 38
150000003839 salts Chemical class 0.000 claims abstract description 25
-1 p-nitrobenzyl ester Chemical class 0.000 claims abstract description 20
HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims abstract description 19
238000002360 preparation method Methods 0.000 claims abstract description 16
125000000217 alkyl group Chemical group 0.000 claims abstract description 10
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 10
HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims abstract description 10
229960003324 clavulanic acid Drugs 0.000 claims abstract description 10
239000003054 catalyst Substances 0.000 claims abstract description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 6
BQPIGGFYSBELGY-UHFFFAOYSA-N mercury(2+) Chemical compound [Hg+2] BQPIGGFYSBELGY-UHFFFAOYSA-N 0.000 claims abstract 2
FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 claims description 20
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
229940090805 clavulanate Drugs 0.000 claims description 13
239000000126 substance Substances 0.000 claims description 13
BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical group CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 claims description 11
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 6
238000003776 cleavage reaction Methods 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 6
230000007017 scission Effects 0.000 claims description 6
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
235000019270 ammonium chloride Nutrition 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 4
AZUFHGGGPUUXKI-FLFDDASRSA-N benzyl (2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O=C([C@@H]1N2C(=O)C[C@H]2O\C1=C/CO)OCC1=CC=CC=C1 AZUFHGGGPUUXKI-FLFDDASRSA-N 0.000 claims description 4
239000003638 chemical reducing agent Substances 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
150000001342 alkaline earth metals Chemical class 0.000 claims description 3
150000003863 ammonium salts Chemical class 0.000 claims description 3
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 3
229910052744 lithium Inorganic materials 0.000 claims description 3
125000006502 nitrobenzyl group Chemical group 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
XDHOEHJVXXTEDV-HWKANZROSA-N (e)-1-ethoxyprop-1-ene Chemical compound CCO\C=C\C XDHOEHJVXXTEDV-HWKANZROSA-N 0.000 claims description 2
125000003277 amino group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims 3
229910052783 alkali metal Inorganic materials 0.000 claims 2
150000001340 alkali metals Chemical class 0.000 claims 2
125000001183 hydrocarbyl group Chemical group 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
239000000243 solution Substances 0.000 description 20
239000000203 mixture Substances 0.000 description 17
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
239000002904 solvent Substances 0.000 description 12
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000000047 product Substances 0.000 description 6
238000004440 column chromatography Methods 0.000 description 5
101150041968 CDC13 gene Proteins 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
239000010410 layer Substances 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
244000166102 Eucalyptus leucoxylon Species 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
229960000723 ampicillin Drugs 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
238000006722 reduction reaction Methods 0.000 description 2
239000007787 solid Substances 0.000 description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
229920002554 vinyl polymer Polymers 0.000 description 2
UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 1
ZKJNETINGMOHJG-UHFFFAOYSA-N 1-prop-1-enoxyprop-1-ene Chemical class CC=COC=CC ZKJNETINGMOHJG-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 1
229930186147 Cephalosporin Natural products 0.000 description 1
OPFTUNCRGUEPRZ-QLFBSQMISA-N Cyclohexane Natural products CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 1
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
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 1
241000588748 Klebsiella Species 0.000 description 1
229940123930 Lactamase inhibitor Drugs 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
241000588770 Proteus mirabilis Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
239000002253 acid Substances 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229940124587 cephalosporin Drugs 0.000 description 1
150000001780 cephalosporins Chemical class 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000013058 crude material Substances 0.000 description 1
POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical class CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
XJRBAMWJDBPFIM-UHFFFAOYSA-N methyl vinyl ether Chemical compound COC=C XJRBAMWJDBPFIM-UHFFFAOYSA-N 0.000 description 1
244000005700 microbiome Species 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
238000010992 reflux Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D503/00—Heterocyclic compounds containing 4-oxa-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxapenicillins, clavulanic acid derivatives; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- 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)
Communicable Diseases (AREA)
Oncology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Cephalosporin Compounds (AREA)

CA308,302A 1977-08-04 1978-07-27 COMPOSES DE TYPE .beta.-LACTAME Expired CA1107739A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000368746A CA1121360A (fr)	1977-08-04	1981-01-16	COMPOSES DE .beta.-LACTAM

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB3269977		1977-08-04
GB32699/77		1977-08-04

Publications (1)

Publication Number	Publication Date
CA1107739A true CA1107739A (fr)	1981-08-25

Family

ID=10342695

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA308,302A Expired CA1107739A (fr)	1977-08-04	1978-07-27	COMPOSES DE TYPE .beta.-LACTAME

Country Status (6)

Country	Link
EP (1)	EP0000804B1 (fr)
JP (1)	JPS5427595A (fr)
CA (1)	CA1107739A (fr)
DE (1)	DE2862385D1 (fr)
ES (1)	ES472335A1 (fr)
IT (1)	IT1106618B (fr)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1501643A (en) *	1974-10-28	1978-02-22	Beecham Group Ltd	Antibacterial substituted azetidinones
GB1565209A (en) *	1975-10-13	1980-04-16	Beecham Group Ltd	Clavulanic acid derivatives
US4230622A (en) *	1975-12-17	1980-10-28	Glaxo Laboratories Limited	Halogen derivatives of clavulaic acid

1978
- 1978-07-10 EP EP78300135A patent/EP0000804B1/fr not_active Expired
- 1978-07-10 DE DE7878300135T patent/DE2862385D1/de not_active Expired
- 1978-07-27 CA CA308,302A patent/CA1107739A/fr not_active Expired
- 1978-08-01 JP JP9501178A patent/JPS5427595A/ja active Pending
- 1978-08-02 IT IT50575/78A patent/IT1106618B/it active
- 1978-08-03 ES ES472335A patent/ES472335A1/es not_active Expired

Also Published As

Publication number	Publication date
JPS5427595A (en)	1979-03-01
EP0000804B1 (fr)	1984-03-07
IT1106618B (it)	1985-11-11
ES472335A1 (es)	1980-03-01
DE2862385D1 (en)	1984-04-12
IT7850575A0 (it)	1978-08-02
EP0000804A1 (fr)	1979-02-21

Legal Events

Date	Code	Title	Description
1998-08-25	MKEX	Expiry

Publication	Publication Date	Title
EP0008497B1 (fr)	1984-10-24	Composés de bêta-lactame, leur préparation et compositions pharmaceutiques les contenant
DD156533A5 (de)	1982-09-01	Verfahren zur herstellung von 3-iodmethylcephalosporinen
EP0008514B1 (fr)	1982-01-20	Dérivés antibactériens de bêta-lactames, compositions les contenant et un procédé pour leur préparation
US4122262A (en)	1978-10-24	Intermediates and methods for preparing 7-acylamino-8-oxo-oxa-1-azabicyclo[4.2.0]octane-2-carboxylic acid derivatives
US4296236A (en)	1981-10-20	7-(or 6-) Substituted-7-(or 6-)acylimino cephalosporin (or penicillin) compounds
CA1107739A (fr)	1981-08-25	COMPOSES DE TYPE .beta.-LACTAME
US4347355A (en)	1982-08-31	Inhibitors of transpeptidase
CA1136138A (fr)	1982-11-23	Analogues de la cephalosporine et methodes de preparation
CA1171415A (fr)	1984-07-24	Carbapenams et carbapen-2-ems; procedes
FI75165C (fi)	1988-05-09	Foerbaettrat foerfarande foer framstaellning av penicillansyraklormetylestrar.
CA1121360A (fr)	1982-04-06	COMPOSES DE .beta.-LACTAM
KR900005046B1 (ko)	1990-07-18	페니실린 유도체의 제조방법
DE3007298A1 (de)	1981-09-03	Verfahren zur herstellung von azetidinonen und deren verwendung
EP0185221B1 (fr)	1990-09-26	Procédé pour la préparation de dérivés d'aminothiazolylacide acétique
CH648850A5 (de)	1985-04-15	Penicillansaeure-derivate, verfahren zu ihrer herstellung und solche derivate enthaltende arzneimittel.
GB2143822A (en)	1985-02-20	Preparation of 3-exomethylene cephalosporins
EP0006589A1 (fr)	1980-01-09	Composés de béta-lactames
EP0002370B1 (fr)	1983-05-11	Procédé pour la préparation de derivés ether de l'acide clavulanique
EP0104010B1 (fr)	1986-04-30	Intermédiaires pour dérivés d'acide clavulanique
EP0033209B1 (fr)	1984-06-13	Composés dérivés de bêta-lactame, leur préparation et leur utilisation
US4683300A (en)	1987-07-28	Deadcat reaction for making 9-deoxy-9-isocyanato clavulanates
FI71562B (fi)	1986-10-10	Foerfarande foer framstaellning av 6-beta-substituerade penicillansyra derivat och saosom mellanprodukter anvaendbara 6-perfluoralkylsulfonyloxipenicillansyraderivat
EP0122002B1 (fr)	1987-04-15	Procédé de préparation de dérivés d'azétidinone
EP0009302B1 (fr)	1983-10-26	Dérivés de l'acide clavulanique et procédé pour leur préparation
EP0397212A1 (fr)	1990-11-14	Procédé de préparation de céphalosporines