NO802713L - Fremgangsmaate til fremstilling av racemiske eller optisk aktive cefalosporin-analoge karbacefemforbindelser eller farmaseutisk akseptable salter derav - Google Patents

Fremgangsmaate til fremstilling av racemiske eller optisk aktive cefalosporin-analoge karbacefemforbindelser eller farmaseutisk akseptable salter derav

Info

Publication number: NO802713L
Authority: NO; Norway
Prior art keywords: group; carbon atoms; denotes; formula; hydrogen atom
Prior art date: 1979-09-13

Application number

NO802713A

Other languages

English (en)

Norwegian (no)

Inventor

Tadashi Hirata

Takehiro Ogasa

Shigeru Kobayashi

Kiyoshi Sato

Chikahiro Urakawa

Akira Sato

Yukio Hashimoto

Seigo Takasawa

Original Assignee

Kyowa Hakko Kogyo Kk

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.)

1979-09-13

Filing date

1980-09-12

Publication date

1981-03-16

1979-09-13 Priority claimed from JP11672079A external-priority patent/JPS5640683A/ja

1979-10-25 Priority claimed from JP13698779A external-priority patent/JPS5661378A/ja

1980-02-23 Priority claimed from JP2203580A external-priority patent/JPS56118084A/ja

1980-09-12 Application filed by Kyowa Hakko Kogyo Kk filed Critical Kyowa Hakko Kogyo Kk

1981-03-16 Publication of NO802713L publication Critical patent/NO802713L/no

Links

150000001875 compounds Chemical class 0.000 title claims description 159
238000000034 method Methods 0.000 title claims description 47
229930186147 Cephalosporin Natural products 0.000 title claims description 27
229940124587 cephalosporin Drugs 0.000 title claims description 27
150000001780 cephalosporins Chemical class 0.000 title claims description 27
238000002360 preparation method Methods 0.000 title claims description 22
150000003839 salts Chemical class 0.000 title claims description 14
125000004432 carbon atom Chemical group C* 0.000 claims description 81
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 64
125000000217 alkyl group Chemical group 0.000 claims description 50
-1 cyanomethyl group Chemical group 0.000 claims description 50
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
125000006239 protecting group Chemical group 0.000 claims description 29
125000002252 acyl group Chemical group 0.000 claims description 23
125000003277 amino group Chemical group 0.000 claims description 19
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 15
125000005843 halogen group Chemical group 0.000 claims description 11
125000001424 substituent group Chemical group 0.000 claims description 11
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
125000000623 heterocyclic group Chemical group 0.000 claims description 8
229910052717 sulfur Inorganic materials 0.000 claims description 8
125000004434 sulfur atom Chemical group 0.000 claims description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
125000004423 acyloxy group Chemical group 0.000 claims description 6
125000003342 alkenyl group Chemical group 0.000 claims description 6
125000000304 alkynyl group Chemical group 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 6
125000005002 aryl methyl group Chemical group 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
125000000335 thiazolyl group Chemical group 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
239000001257 hydrogen Substances 0.000 claims description 5
125000004430 oxygen atom Chemical group O* 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 claims description 4
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 4
125000002541 furyl group Chemical group 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
125000001786 isothiazolyl group Chemical group 0.000 claims description 4
125000000842 isoxazolyl group Chemical group 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
125000002971 oxazolyl group Chemical group 0.000 claims description 4
125000003226 pyrazolyl group Chemical group 0.000 claims description 4
125000004076 pyridyl group Chemical group 0.000 claims description 4
125000000168 pyrrolyl group Chemical group 0.000 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
125000001544 thienyl group Chemical group 0.000 claims description 4
125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims description 3
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 3
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
229910052783 alkali metal Inorganic materials 0.000 claims description 3
150000001340 alkali metals Chemical class 0.000 claims description 3
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical class 0.000 claims description 3
125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
238000001727 in vivo Methods 0.000 claims description 3
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
125000003373 pyrazinyl group Chemical group 0.000 claims description 3
125000002098 pyridazinyl group Chemical group 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 3
125000003107 substituted aryl group Chemical group 0.000 claims description 3
125000004306 triazinyl group Chemical group 0.000 claims description 3
125000001425 triazolyl group Chemical group 0.000 claims description 3
125000000169 tricyclic heterocycle group Chemical group 0.000 claims description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
239000000203 mixture Substances 0.000 description 94
239000000243 solution Substances 0.000 description 93
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 72
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 70
229910001868 water Inorganic materials 0.000 description 60
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 40
238000006243 chemical reaction Methods 0.000 description 38
239000000047 product Substances 0.000 description 36
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 35
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 32
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
238000005481 NMR spectroscopy Methods 0.000 description 26
239000002904 solvent Substances 0.000 description 26
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
238000001816 cooling Methods 0.000 description 23
238000003756 stirring Methods 0.000 description 23
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
238000010828 elution Methods 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
239000011541 reaction mixture Substances 0.000 description 16
108090000790 Enzymes Proteins 0.000 description 15
102000004190 Enzymes Human genes 0.000 description 15
210000004027 cell Anatomy 0.000 description 15
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
239000000843 powder Substances 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
239000000741 silica gel Substances 0.000 description 14
229910002027 silica gel Inorganic materials 0.000 description 14
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
239000013078 crystal Substances 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
239000012141 concentrate Substances 0.000 description 11
239000000758 substrate Substances 0.000 description 11
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
244000005700 microbiome Species 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000010410 layer Substances 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
150000008065 acid anhydrides Chemical class 0.000 description 8
150000003855 acyl compounds Chemical class 0.000 description 8
239000000463 material Substances 0.000 description 8
229920006395 saturated elastomer Polymers 0.000 description 8
239000011780 sodium chloride Substances 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 7
238000005917 acylation reaction Methods 0.000 description 7
230000000844 anti-bacterial effect Effects 0.000 description 7
210000005056 cell body Anatomy 0.000 description 7
239000000284 extract Substances 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
238000001914 filtration Methods 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
235000010633 broth Nutrition 0.000 description 6
238000005119 centrifugation Methods 0.000 description 6
238000009833 condensation Methods 0.000 description 6
230000005494 condensation Effects 0.000 description 6
230000020176 deacylation Effects 0.000 description 6
238000005947 deacylation reaction Methods 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
238000002844 melting Methods 0.000 description 6
230000008018 melting Effects 0.000 description 6
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 6
238000000746 purification Methods 0.000 description 6
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 6
239000000725 suspension Substances 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
230000010933 acylation Effects 0.000 description 5
239000008367 deionised water Substances 0.000 description 5
229910021641 deionized water Inorganic materials 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000002808 molecular sieve Substances 0.000 description 5
239000008363 phosphate buffer Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
230000008569 process Effects 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
239000007858 starting material Substances 0.000 description 5
238000004809 thin layer chromatography Methods 0.000 description 5
229930182555 Penicillin Natural products 0.000 description 4
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 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
239000012043 crude product Substances 0.000 description 4
235000019441 ethanol Nutrition 0.000 description 4
238000000605 extraction Methods 0.000 description 4
150000004820 halides Chemical class 0.000 description 4
239000007788 liquid Substances 0.000 description 4
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 4
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 4
230000003287 optical effect Effects 0.000 description 4
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
229940049954 penicillin Drugs 0.000 description 4
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
CDEZBCPZTYUSSW-RPDRRWSUSA-N (4s,6r,7s)-7-amino-4-hydroxy-8-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1[C@H](O)C=C(C(O)=O)N2C(=O)[C@@H](N)[C@H]21 CDEZBCPZTYUSSW-RPDRRWSUSA-N 0.000 description 3
SUHXTVABLHHRST-UHFFFAOYSA-N 2-azidoacetyl chloride Chemical compound ClC(=O)CN=[N+]=[N-] SUHXTVABLHHRST-UHFFFAOYSA-N 0.000 description 3
TVZRAEYQIKYCPH-UHFFFAOYSA-N 3-(trimethylsilyl)propane-1-sulfonic acid Chemical compound C[Si](C)(C)CCCS(O)(=O)=O TVZRAEYQIKYCPH-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
229940126062 Compound A Drugs 0.000 description 3
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
108010093096 Immobilized Enzymes Proteins 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
239000002262 Schiff base Substances 0.000 description 3
150000004753 Schiff bases Chemical class 0.000 description 3
239000003242 anti bacterial agent Substances 0.000 description 3
230000000845 anti-microbial effect Effects 0.000 description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
238000010531 catalytic reduction reaction Methods 0.000 description 3
238000001035 drying Methods 0.000 description 3
238000006911 enzymatic reaction Methods 0.000 description 3
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 3
238000002955 isolation Methods 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
DIFLXBCYHDZYRY-UHFFFAOYSA-N tert-butyl 2-amino-2-diethoxyphosphorylacetate Chemical compound CCOP(=O)(OCC)C(N)C(=O)OC(C)(C)C DIFLXBCYHDZYRY-UHFFFAOYSA-N 0.000 description 3
125000004665 trialkylsilyl group Chemical group 0.000 description 3
OJFHAFJGQZSFKT-ONEGZZNKSA-N (e)-4,4-dimethoxybut-2-enal Chemical compound COC(OC)\C=C\C=O OJFHAFJGQZSFKT-ONEGZZNKSA-N 0.000 description 2
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
PPXUUPXQWDQNGO-UHFFFAOYSA-N 2-azidoacetic acid Chemical compound OC(=O)CN=[N+]=[N-] PPXUUPXQWDQNGO-UHFFFAOYSA-N 0.000 description 2
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 2
FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
125000004008 6 membered carbocyclic group Chemical group 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
108090000371 Esterases Proteins 0.000 description 2
241000588773 Kluyvera cryocrescens Species 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
239000000370 acceptor Substances 0.000 description 2
238000002814 agar dilution Methods 0.000 description 2
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
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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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D463/00—Heterocyclic compounds containing 1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D463/10—Heterocyclic compounds containing 1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D463/14—Heterocyclic compounds containing 1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hetero atoms directly attached in position 7
- C07D463/16—Nitrogen atoms
- C07D463/18—Nitrogen atoms further acylated by radicals derived from carboxylic acids or by nitrogen or sulfur analogues thereof
- C07D463/20—Nitrogen atoms further acylated by radicals derived from carboxylic acids or by nitrogen or sulfur analogues thereof with the acylating radicals further substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D463/22—Nitrogen atoms further acylated by radicals derived from carboxylic acids or by nitrogen or sulfur analogues thereof with the acylating radicals further substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen further substituted by nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/568—Four-membered rings
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Wood Science & Technology (AREA)
Zoology (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Microbiology (AREA)
Biotechnology (AREA)
Molecular Biology (AREA)
Bioinformatics & Cheminformatics (AREA)
General Engineering & Computer Science (AREA)
Genetics & Genomics (AREA)
Cephalosporin Compounds (AREA)

NO802713A 1979-09-13 1980-09-12 Fremgangsmaate til fremstilling av racemiske eller optisk aktive cefalosporin-analoge karbacefemforbindelser eller farmaseutisk akseptable salter derav NO802713L (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
JP11672079A JPS5640683A (en)	1979-09-13	1979-09-13	Cephalosporin analogue
JP13698779A JPS5661378A (en)	1979-10-25	1979-10-25	Optically active cephalosporin analog
JP2203580A JPS56118084A (en)	1980-02-23	1980-02-23	Optically active cephalosporin analogue

Publications (1)

Publication Number	Publication Date
NO802713L true NO802713L (no)	1981-03-16

Family

ID=27283683

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO802713A NO802713L (no)	1979-09-13	1980-09-12	Fremgangsmaate til fremstilling av racemiske eller optisk aktive cefalosporin-analoge karbacefemforbindelser eller farmaseutisk akseptable salter derav

Country Status (6)

Country	Link
EP (1)	EP0025602B1 (da)
CA (1)	CA1178957A (da)
DE (1)	DE3069832D1 (da)
DK (1)	DK389080A (da)
ES (1)	ES495035A0 (da)
NO (1)	NO802713L (da)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4347183A (en) *	1981-02-02	1982-08-31	Schering Corporation	Process for the synthesis of penems and carbapenems
PH19170A (en) *	1981-03-30	1986-01-16	Squibb & Sons Inc	2 oxo-1-(substituted phosphorous)azetidines
EP0082501A1 (en) *	1981-12-18	1983-06-29	Kyowa Hakko Kogyo Co., Ltd	Beta-lactam compound and a pharmaceutical composition containing the same
EP0112481A1 (en) *	1982-11-12	1984-07-04	Kyowa Hakko Kogyo Co., Ltd	Beta-lactam compound
DE3803169A1 (de)	1988-02-03	1989-08-17	Bayer Ag	Ss-lactam-antibiotika, verfahren zu ihrer herstellung und ihre verwendung als und in arzneimitteln
US5099015A (en) *	1991-01-10	1992-03-24	Eli Lilly And Company	Trifluoromethyl 1-carba(1-dethia)cephems

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4012383A (en) *	1975-01-02	1977-03-15	Bristol-Myers Company	Δ2,3 -1,4-morpholine-2-carboxylic acids and derivatives thereof useful in preparation of antibacteria agents
US4089956A (en) *	1976-09-08	1978-05-16	Smithkline Corporation	7-Acylamino-8-oxo-3-oxa-1-azabicyclo[4.2.0]octane-2-carboxylic acid derivatives and bactericidal compositions and use thereof
JPS54128591A (en) *	1978-03-25	1979-10-05	Kyowa Hakko Kogyo Co Ltd	Cephalosporin analog

1980
- 1980-09-12 DE DE8080105492T patent/DE3069832D1/de not_active Expired
- 1980-09-12 NO NO802713A patent/NO802713L/no unknown
- 1980-09-12 DK DK389080A patent/DK389080A/da not_active Application Discontinuation
- 1980-09-12 EP EP80105492A patent/EP0025602B1/en not_active Expired
- 1980-09-12 ES ES495035A patent/ES495035A0/es active Granted
- 1980-09-15 CA CA000360255A patent/CA1178957A/en not_active Expired

Also Published As

Publication number	Publication date
DE3069832D1 (en)	1985-01-31
DK389080A (da)	1981-03-14
EP0025602A1 (en)	1981-03-25
ES8200689A1 (es)	1981-11-16
ES495035A0 (es)	1981-11-16
EP0025602B1 (en)	1984-12-19
CA1178957A (en)	1984-12-04

Publication	Publication Date	Title
US4556559A (en)	1985-12-03	Antibiotics
US4110165A (en)	1978-08-29	Process for the production of clavulanic acid
JPS5946954B2 (ja)	1984-11-15	抗生物質の製法
US4529720A (en)	1985-07-16	Antibiotic from Streptomyces clavulicerus
US6031093A (en)	2000-02-29	Solid salts of clavulanic acid
EP0014476B1 (en)	1983-08-10	Optically active acylated cephalosporin analogs, processes for their preparation and pharmaceutical compositions comprising them
US4335211A (en)	1982-06-15	Process for producing optically active cephalosporin analogs
EP0527686B1 (en)	1997-10-08	Cephalosporin derivatives
EP0025602B1 (en)	1984-12-19	Acylated cephalosporin analogs, process for their preparation and pharmaceutical compositions comprising them
US4525353A (en)	1985-06-25	Antibiotics
EP0014475B1 (en)	1984-02-15	Optically active cephalosporin analogs, process for their preparation and their use in the preparation of pharmaceutical compositions
KR900002042B1 (ko)	1990-03-31	3-치환된 세팔로스포린의 제조방법
US4140764A (en)	1979-02-20	β-Lactamase inhibitors and process for their preparation
EP0027882B1 (en)	1985-01-02	Optically active cephalosporin analogs, process for their preparation and their use
US4302540A (en)	1981-11-24	Process of producing optically active cephalosporin analogs by enzyme selective deacylation
US4663450A (en)	1987-05-05	Optically active cephalosporin analogs
INOUYE et al.	1983	Discovery, isolation and structure of novel cephamycins of Streptomyces chartreusis
JPH0240669B2 (da)	1990-09-12
US4755596A (en)	1988-07-05	Optically active carbacephems
US4061649A (en)	1977-12-06	Clavulanic acid sulphates
US4316958A (en)	1982-02-23	Process for producing optically active cephalosporin analogs
JPH0240667B2 (da)	1990-09-12
US4123540A (en)	1978-10-31	Isoclavulanic acid as an antibacterial and a β-lactamase inhibitor
NO744526L (da)	1975-07-14
CA1074325A (en)	1980-03-25	Clavulanic acid and its salts