CN1795197A - 头孢菌素类化合物 - Google Patents
头孢菌素类化合物 Download PDFInfo
- Publication number
- CN1795197A CN1795197A CNA2004800146370A CN200480014637A CN1795197A CN 1795197 A CN1795197 A CN 1795197A CN A2004800146370 A CNA2004800146370 A CN A2004800146370A CN 200480014637 A CN200480014637 A CN 200480014637A CN 1795197 A CN1795197 A CN 1795197A
- Authority
- CN
- China
- Prior art keywords
- group
- perhaps
- acyl group
- compound
- alkyl
- Prior art date
- 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.)
- Granted
Links
- -1 Cephem compound Chemical class 0.000 title claims abstract description 20
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 64
- 150000001875 compounds Chemical class 0.000 claims abstract description 36
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 25
- 150000002148 esters Chemical class 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 238000004519 manufacturing process Methods 0.000 claims abstract description 15
- 244000005700 microbiome Species 0.000 claims abstract description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 150000002367 halogens Chemical group 0.000 claims abstract description 8
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 102000004190 Enzymes Human genes 0.000 claims description 45
- 108090000790 Enzymes Proteins 0.000 claims description 45
- 241000228150 Penicillium chrysogenum Species 0.000 claims description 45
- 125000002252 acyl group Chemical group 0.000 claims description 39
- 229940124587 cephalosporin Drugs 0.000 claims description 36
- 230000001580 bacterial effect Effects 0.000 claims description 34
- 239000001301 oxygen Substances 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 31
- 102000008109 Mixed Function Oxygenases Human genes 0.000 claims description 17
- 108010074633 Mixed Function Oxygenases Proteins 0.000 claims description 17
- 238000012262 fermentative production Methods 0.000 claims description 10
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 239000005864 Sulphur Substances 0.000 claims description 7
- 239000002243 precursor Substances 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- MIFYHUACUWQUKT-UHFFFAOYSA-N Isopenicillin N Natural products OC(=O)C1C(C)(C)SC2C(NC(=O)CCCC(N)C(O)=O)C(=O)N21 MIFYHUACUWQUKT-UHFFFAOYSA-N 0.000 claims description 5
- 238000004176 ammonification Methods 0.000 claims description 4
- 229960002682 cefoxitin Drugs 0.000 claims description 4
- 238000013467 fragmentation Methods 0.000 claims description 4
- 238000006062 fragmentation reaction Methods 0.000 claims description 4
- 230000033444 hydroxylation Effects 0.000 claims description 4
- 238000005805 hydroxylation reaction Methods 0.000 claims description 4
- ODJQKYXPKWQWNK-UHFFFAOYSA-N 3,3'-Thiobispropanoic acid Chemical compound OC(=O)CCSCCC(O)=O ODJQKYXPKWQWNK-UHFFFAOYSA-N 0.000 claims description 3
- ZCIBQBYQTHJFFP-UHFFFAOYSA-N C(CC)(=O)O.[S] Chemical compound C(CC)(=O)O.[S] ZCIBQBYQTHJFFP-UHFFFAOYSA-N 0.000 claims description 3
- 238000010170 biological method Methods 0.000 claims description 2
- 230000002255 enzymatic effect Effects 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 238000006049 ring expansion reaction Methods 0.000 claims description 2
- MIFYHUACUWQUKT-QSKNDCFUSA-N isopenicillin n Chemical compound OC(=O)[C@@H]1C(C)(C)S[C@H]2[C@H](NC(=O)CCC[C@H](N)C(O)=O)C(=O)N21 MIFYHUACUWQUKT-QSKNDCFUSA-N 0.000 claims 3
- GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical compound [Na+].N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)CC1=CC=CS1 GNWUOVJNSFPWDD-XMZRARIVSA-M 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 16
- 230000036983 biotransformation Effects 0.000 abstract description 3
- 125000003831 tetrazolyl group Chemical group 0.000 abstract description 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 1
- 239000011593 sulfur Substances 0.000 abstract 1
- 108020004414 DNA Proteins 0.000 description 30
- 239000000243 solution Substances 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000001914 filtration Methods 0.000 description 13
- 229930186147 Cephalosporin Natural products 0.000 description 12
- 101150033696 cmcH gene Proteins 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 101150091913 cefE gene Proteins 0.000 description 11
- 239000012634 fragment Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 101710107944 Isopenicillin N synthase Proteins 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 241000187433 Streptomyces clavuligerus Species 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 10
- 238000003752 polymerase chain reaction Methods 0.000 description 10
- 241000228431 Acremonium chrysogenum Species 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 150000001780 cephalosporins Chemical class 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 241000588724 Escherichia coli Species 0.000 description 7
- 239000013611 chromosomal DNA Substances 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 238000012239 gene modification Methods 0.000 description 7
- 230000005017 genetic modification Effects 0.000 description 7
- 235000013617 genetically modified food Nutrition 0.000 description 7
- 101150022041 penDE gene Proteins 0.000 description 7
- 241000187390 Amycolatopsis lactamdurans Species 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 6
- 238000000855 fermentation Methods 0.000 description 6
- 230000004151 fermentation Effects 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- 241000233866 Fungi Species 0.000 description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 230000002779 inactivation Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 150000003952 β-lactams Chemical class 0.000 description 5
- LXWBXEWUSAABOA-UHFFFAOYSA-N Cephamycin-C Natural products S1CC(COC(N)=O)=C(C(O)=O)N2C(=O)C(OC)(NC(=O)CCCC(N)C(O)=O)C21 LXWBXEWUSAABOA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241001531966 Lysobacter lactamgenus Species 0.000 description 4
- 241000191938 Micrococcus luteus Species 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
- LXWBXEWUSAABOA-VXSYNFHWSA-N cephamycin C Chemical compound S1CC(COC(N)=O)=C(C(O)=O)N2C(=O)[C@@](OC)(NC(=O)CCC[C@@H](N)C(O)=O)[C@H]21 LXWBXEWUSAABOA-VXSYNFHWSA-N 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000013067 intermediate product Substances 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- JPSKCQCQZUGWNM-UHFFFAOYSA-N 2,7-Oxepanedione Chemical compound O=C1CCCCC(=O)O1 JPSKCQCQZUGWNM-UHFFFAOYSA-N 0.000 description 3
- 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 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000351920 Aspergillus nidulans Species 0.000 description 3
- 235000014469 Bacillus subtilis Nutrition 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 241000228143 Penicillium Species 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 101150044235 cefF gene Proteins 0.000 description 3
- WZOZEZRFJCJXNZ-ZBFHGGJFSA-N cefoxitin Chemical compound N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)CC1=CC=CS1 WZOZEZRFJCJXNZ-ZBFHGGJFSA-N 0.000 description 3
- 229960004755 ceftriaxone Drugs 0.000 description 3
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- FMZXNVLFJHCSAF-DNVCBOLYSA-N (6R,7R)-3-[(4-carbamoyl-1-pyridin-1-iumyl)methyl]-8-oxo-7-[(1-oxo-2-thiophen-2-ylethyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC(C(=O)N)=CC=[N+]1CC1=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)CC=3SC=CC=3)[C@H]2SC1 FMZXNVLFJHCSAF-DNVCBOLYSA-N 0.000 description 2
- 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 2
- 108700016155 Acyl transferases Proteins 0.000 description 2
- 102000057234 Acyl transferases Human genes 0.000 description 2
- UQLLWWBDSUHNEB-CZUORRHYSA-N Cefaprin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CSC1=CC=NC=C1 UQLLWWBDSUHNEB-CZUORRHYSA-N 0.000 description 2
- QYQDKDWGWDOFFU-IUODEOHRSA-N Cefotiam Chemical compound CN(C)CCN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CC=3N=C(N)SC=3)[C@H]2SC1 QYQDKDWGWDOFFU-IUODEOHRSA-N 0.000 description 2
- JFPVXVDWJQMJEE-QMTHXVAHSA-N Cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)C(=NOC)C1=CC=CO1 JFPVXVDWJQMJEE-QMTHXVAHSA-N 0.000 description 2
- KEJCWVGMRLCZQQ-YJBYXUATSA-N Cefuroxime axetil Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(=O)OC(C)OC(C)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 KEJCWVGMRLCZQQ-YJBYXUATSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 108700005088 Fungal Genes Proteins 0.000 description 2
- 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 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 241000187747 Streptomyces Species 0.000 description 2
- 108090000992 Transferases Proteins 0.000 description 2
- 102000004357 Transferases Human genes 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 101150035092 cefD gene Proteins 0.000 description 2
- RRYMAQUWDLIUPV-BXKDBHETSA-N cefacetrile Chemical group S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CC#N)[C@@H]12 RRYMAQUWDLIUPV-BXKDBHETSA-N 0.000 description 2
- 229960005361 cefaclor Drugs 0.000 description 2
- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 description 2
- CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 description 2
- 229960003866 cefaloridine Drugs 0.000 description 2
- 229960003012 cefamandole Drugs 0.000 description 2
- OLVCFLKTBJRLHI-AXAPSJFSSA-N cefamandole Chemical compound CN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)[C@H](O)C=3C=CC=CC=3)[C@H]2SC1 OLVCFLKTBJRLHI-AXAPSJFSSA-N 0.000 description 2
- 229960004350 cefapirin Drugs 0.000 description 2
- UOCJDOLVGGIYIQ-PBFPGSCMSA-N cefatrizine Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)[C@H](N)C=2C=CC(O)=CC=2)CC=1CSC=1C=NNN=1 UOCJDOLVGGIYIQ-PBFPGSCMSA-N 0.000 description 2
- 229960002420 cefatrizine Drugs 0.000 description 2
- VTLCNEGVSVJLDN-MLGOLLRUSA-N cefazedone Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3C=C(Cl)C(=O)C(Cl)=C3)[C@H]2SC1 VTLCNEGVSVJLDN-MLGOLLRUSA-N 0.000 description 2
- 229960005312 cefazedone Drugs 0.000 description 2
- 229960001817 cefbuperazone Drugs 0.000 description 2
- SMSRCGPDNDCXFR-CYWZMYCQSA-N cefbuperazone Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H]([C@H](C)O)C(=O)N[C@]1(OC)C(=O)N2C(C(O)=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 SMSRCGPDNDCXFR-CYWZMYCQSA-N 0.000 description 2
- 229960003719 cefdinir Drugs 0.000 description 2
- RTXOFQZKPXMALH-GHXIOONMSA-N cefdinir Chemical compound S1C(N)=NC(C(=N\O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 RTXOFQZKPXMALH-GHXIOONMSA-N 0.000 description 2
- 229960002142 cefditoren pivoxil Drugs 0.000 description 2
- HVFLCNVBZFFHBT-ZKDACBOMSA-N cefepime Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1C[N+]1(C)CCCC1 HVFLCNVBZFFHBT-ZKDACBOMSA-N 0.000 description 2
- 229960002100 cefepime Drugs 0.000 description 2
- 229960002129 cefixime Drugs 0.000 description 2
- OKBVVJOGVLARMR-QSWIMTSFSA-N cefixime Chemical compound S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QSWIMTSFSA-N 0.000 description 2
- 229960003791 cefmenoxime Drugs 0.000 description 2
- HJJDBAOLQAWBMH-YCRCPZNHSA-N cefmenoxime Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NN=NN1C HJJDBAOLQAWBMH-YCRCPZNHSA-N 0.000 description 2
- 229960003585 cefmetazole Drugs 0.000 description 2
- SNBUBQHDYVFSQF-HIFRSBDPSA-N cefmetazole Chemical compound S([C@@H]1[C@@](C(N1C=1C(O)=O)=O)(NC(=O)CSCC#N)OC)CC=1CSC1=NN=NN1C SNBUBQHDYVFSQF-HIFRSBDPSA-N 0.000 description 2
- 229960002025 cefminox Drugs 0.000 description 2
- JSDXOWVAHXDYCU-VXSYNFHWSA-N cefminox Chemical compound S([C@@H]1[C@@](C(N1C=1C(O)=O)=O)(NC(=O)CSC[C@@H](N)C(O)=O)OC)CC=1CSC1=NN=NN1C JSDXOWVAHXDYCU-VXSYNFHWSA-N 0.000 description 2
- 229960001958 cefodizime Drugs 0.000 description 2
- XDZKBRJLTGRPSS-BGZQYGJUSA-N cefodizime Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(C)=C(CC(O)=O)S1 XDZKBRJLTGRPSS-BGZQYGJUSA-N 0.000 description 2
- 229960004489 cefonicid Drugs 0.000 description 2
- DYAIAHUQIPBDIP-AXAPSJFSSA-N cefonicid Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)[C@H](O)C=2C=CC=CC=2)CC=1CSC1=NN=NN1CS(O)(=O)=O DYAIAHUQIPBDIP-AXAPSJFSSA-N 0.000 description 2
- GCFBRXLSHGKWDP-XCGNWRKASA-N cefoperazone Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C(O)=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 GCFBRXLSHGKWDP-XCGNWRKASA-N 0.000 description 2
- 229960004261 cefotaxime Drugs 0.000 description 2
- GPRBEKHLDVQUJE-VINNURBNSA-N cefotaxime Chemical compound N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C(O)=O)=O)C(=O)/C(=N/OC)C1=CSC(N)=N1 GPRBEKHLDVQUJE-VINNURBNSA-N 0.000 description 2
- 229960001242 cefotiam Drugs 0.000 description 2
- 229950010227 cefotiam hexetil Drugs 0.000 description 2
- VVFDMWZLBPUKTD-ZKRNHDOASA-N cefotiam hexetil ester Chemical compound O=C([C@@H](NC(=O)CC=1N=C(N)SC=1)[C@H]1SCC=2CSC=3N(N=NN=3)CCN(C)C)N1C=2C(=O)OC(C)OC(=O)OC1CCCCC1 VVFDMWZLBPUKTD-ZKRNHDOASA-N 0.000 description 2
- 229960005446 cefpiramide Drugs 0.000 description 2
- PWAUCHMQEXVFJR-PMAPCBKXSA-N cefpiramide Chemical compound C1=NC(C)=CC(O)=C1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C(O)=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 PWAUCHMQEXVFJR-PMAPCBKXSA-N 0.000 description 2
- DKOQGJHPHLTOJR-WHRDSVKCSA-N cefpirome Chemical compound N([C@@H]1C(N2C(=C(C[N+]=3C=4CCCC=4C=CC=3)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 DKOQGJHPHLTOJR-WHRDSVKCSA-N 0.000 description 2
- 229960000466 cefpirome Drugs 0.000 description 2
- LTINZAODLRIQIX-FBXRGJNPSA-N cefpodoxime proxetil Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(=O)OC(C)OC(=O)OC(C)C)C(=O)C(=N/OC)\C1=CSC(N)=N1 LTINZAODLRIQIX-FBXRGJNPSA-N 0.000 description 2
- 229960004797 cefpodoxime proxetil Drugs 0.000 description 2
- 229960003202 cefsulodin Drugs 0.000 description 2
- SYLKGLMBLAAGSC-QLVMHMETSA-N cefsulodin Chemical compound C1=CC(C(=O)N)=CC=[N+]1CC1=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)[C@@H](C=3C=CC=CC=3)S(O)(=O)=O)[C@H]2SC1 SYLKGLMBLAAGSC-QLVMHMETSA-N 0.000 description 2
- 229960004086 ceftibuten Drugs 0.000 description 2
- UNJFKXSSGBWRBZ-BJCIPQKHSA-N ceftibuten Chemical compound S1C(N)=NC(C(=C\CC(O)=O)\C(=O)N[C@@H]2C(N3C(=CCS[C@@H]32)C(O)=O)=O)=C1 UNJFKXSSGBWRBZ-BJCIPQKHSA-N 0.000 description 2
- ZBHXIWJRIFEVQY-IHMPYVIRSA-N ceftiofur Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC(=O)C1=CC=CO1 ZBHXIWJRIFEVQY-IHMPYVIRSA-N 0.000 description 2
- 229960005229 ceftiofur Drugs 0.000 description 2
- 229960001991 ceftizoxime Drugs 0.000 description 2
- NNULBSISHYWZJU-LLKWHZGFSA-N ceftizoxime Chemical compound N([C@@H]1C(N2C(=CCS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 NNULBSISHYWZJU-LLKWHZGFSA-N 0.000 description 2
- 229960002620 cefuroxime axetil Drugs 0.000 description 2
- CXHKZHZLDMQGFF-ZSDSSEDPSA-N cefuzonam Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=CN=NS1 CXHKZHZLDMQGFF-ZSDSSEDPSA-N 0.000 description 2
- 229950000807 cefuzonam Drugs 0.000 description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 125000003651 hexanedioyl group Chemical group C(CCCCC(=O)*)(=O)* 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- MIFYHUACUWQUKT-GTQWGBSQSA-N isopenicillin N Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2[C@H](NC(=O)CCC[C@H](N)C(O)=O)C(=O)N21 MIFYHUACUWQUKT-GTQWGBSQSA-N 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 2
- 229940049547 paraxin Drugs 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- WSHJJCPTKWSMRR-RXMQYKEDSA-N penam Chemical compound S1CCN2C(=O)C[C@H]21 WSHJJCPTKWSMRR-RXMQYKEDSA-N 0.000 description 2
- 229940056360 penicillin g Drugs 0.000 description 2
- 229940056367 penicillin v Drugs 0.000 description 2
- 150000002960 penicillins Chemical class 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- FZEVMBJWXHDLDB-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical compound S1CC=CN2C(=O)C[C@H]21 FZEVMBJWXHDLDB-ZCFIWIBFSA-N 0.000 description 1
- WDLWHQDACQUCJR-ZAMMOSSLSA-N (6r,7r)-7-[[(2r)-2-azaniumyl-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(e)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)/C=C/C)C(O)=O)=CC=C(O)C=C1 WDLWHQDACQUCJR-ZAMMOSSLSA-N 0.000 description 1
- LZHSSXWWEBLEOY-UHFFFAOYSA-N 1,1'-biphenyl;diazomethane Chemical compound C=[N+]=[N-].C1=CC=CC=C1C1=CC=CC=C1 LZHSSXWWEBLEOY-UHFFFAOYSA-N 0.000 description 1
- WVPAABNYMHNFJG-QDVBXLKVSA-N 2,2-dimethylpropanoyloxymethyl (6r,7r)-7-[[(z)-2-(2-amino-1,3-thiazol-4-yl)pent-2-enoyl]amino]-3-(carbamoyloxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(=O)OCOC(=O)C(C)(C)C)=O)C(=O)\C(=C/CC)C1=CSC(N)=N1 WVPAABNYMHNFJG-QDVBXLKVSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
- HOMHKBKWSCWJLW-UHFFFAOYSA-N 2-phenoxyacetic acid;potassium Chemical compound [K].OC(=O)COC1=CC=CC=C1 HOMHKBKWSCWJLW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 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 1
- 108010006533 ATP-Binding Cassette Transporters Proteins 0.000 description 1
- 102000005416 ATP-Binding Cassette Transporters Human genes 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 1
- 241001019659 Acremonium <Plectosphaerellaceae> Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 241000203809 Actinomycetales Species 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- DGCSDFQSACULNZ-UHFFFAOYSA-N BrC(C(=O)N=C=O)(Br)Br Chemical compound BrC(C(=O)N=C=O)(Br)Br DGCSDFQSACULNZ-UHFFFAOYSA-N 0.000 description 1
- YFHJGPJJLHOAGK-UHFFFAOYSA-N C1=CC=[C+]C=C1.[K+] Chemical compound C1=CC=[C+]C=C1.[K+] YFHJGPJJLHOAGK-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 240000002228 Cynara humilis Species 0.000 description 1
- 235000005921 Cynara humilis Nutrition 0.000 description 1
- 101710104123 Deacetoxycephalosporin C synthase Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 101150108358 GLAA gene Proteins 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
- 241000863031 Lysobacter Species 0.000 description 1
- 206010027336 Menstruation delayed Diseases 0.000 description 1
- 241000187654 Nocardia Species 0.000 description 1
- 108010073038 Penicillin Amidase Proteins 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 241000228417 Sarocladium strictum Species 0.000 description 1
- 241000015473 Schizothorax griseus Species 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 241000187760 Streptomyces albogriseolus Species 0.000 description 1
- 241001147855 Streptomyces cattleya Species 0.000 description 1
- 241000424942 Streptomyces clavuligerus ATCC 27064 Species 0.000 description 1
- 241000913723 Streptomyces heteromorphus Species 0.000 description 1
- 241000187215 Streptomyces jumonjinensis Species 0.000 description 1
- 241000187395 Streptomyces microflavus Species 0.000 description 1
- 241000913724 Streptomyces panayensis Species 0.000 description 1
- 241001248020 Streptomyces wadayamensis Species 0.000 description 1
- 241000863032 Trieres Species 0.000 description 1
- 108020002494 acetyltransferase Proteins 0.000 description 1
- 102000005421 acetyltransferase Human genes 0.000 description 1
- 108010013491 acyl-CoA-6-aminopenicillanic acid acyltransferase Proteins 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- YAVVGPBYBUYPSR-UHFFFAOYSA-N benzene;oxygen Chemical compound [O].C1=CC=CC=C1 YAVVGPBYBUYPSR-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000003570 biosynthesizing effect Effects 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 230000021235 carbamoylation Effects 0.000 description 1
- 101150019420 cefD1 gene Proteins 0.000 description 1
- 101150085441 cefD2 gene Proteins 0.000 description 1
- FUBBGQLTSCSAON-PBFPGSCMSA-N cefaloglycin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)COC(=O)C)C(O)=O)=CC=CC=C1 FUBBGQLTSCSAON-PBFPGSCMSA-N 0.000 description 1
- 229950004030 cefaloglycin Drugs 0.000 description 1
- 229950005258 cefalonium Drugs 0.000 description 1
- XIURVHNZVLADCM-IUODEOHRSA-N cefalotin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CC1=CC=CS1 XIURVHNZVLADCM-IUODEOHRSA-N 0.000 description 1
- 229960000603 cefalotin Drugs 0.000 description 1
- 229960001139 cefazolin Drugs 0.000 description 1
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 1
- 229950004627 cefcapene pivoxil Drugs 0.000 description 1
- AFZFFLVORLEPPO-UVYJNCLZSA-N cefditoren pivoxil Chemical compound S([C@@H]1[C@@H](C(N1C=1C(=O)OCOC(=O)C(C)(C)C)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1\C=C/C=1SC=NC=1C AFZFFLVORLEPPO-UVYJNCLZSA-N 0.000 description 1
- 229960004682 cefoperazone Drugs 0.000 description 1
- 229960002580 cefprozil Drugs 0.000 description 1
- RDMOROXKXONCAL-UEKVPHQBSA-N cefroxadine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)OC)C(O)=O)=CCC=CC1 RDMOROXKXONCAL-UEKVPHQBSA-N 0.000 description 1
- 229960003844 cefroxadine Drugs 0.000 description 1
- 229960000484 ceftazidime Drugs 0.000 description 1
- ORFOPKXBNMVMKC-DWVKKRMSSA-N ceftazidime Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC(C)(C)C(O)=O)C=2N=C(N)SC=2)CC=1C[N+]1=CC=CC=C1 ORFOPKXBNMVMKC-DWVKKRMSSA-N 0.000 description 1
- XSPUSVIQHBDITA-RKYNPMAHSA-N cefteram Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CN1N=NC(C)=N1 XSPUSVIQHBDITA-RKYNPMAHSA-N 0.000 description 1
- 229950002506 cefteram pivoxil Drugs 0.000 description 1
- DZMVCVMFETWNIU-LDYMZIIASA-N ceftezole Chemical compound O=C([C@@H](NC(=O)CN1N=NN=C1)[C@H]1SC2)N1C(C(=O)O)=C2CSC1=NN=CS1 DZMVCVMFETWNIU-LDYMZIIASA-N 0.000 description 1
- 229960004366 ceftezole Drugs 0.000 description 1
- 229960001668 cefuroxime Drugs 0.000 description 1
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 description 1
- UCKZMPLVLCKKMO-LHLIQPBNSA-N cephamycin Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](C)[C@]21OC UCKZMPLVLCKKMO-LHLIQPBNSA-N 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- 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 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000012084 conversion product Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 101150073906 gpdA gene Proteins 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 101150074325 pcbC gene Proteins 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- ABVRVIZBZKUTMK-JSYANWSFSA-M potassium clavulanate Chemical compound [K+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 ABVRVIZBZKUTMK-JSYANWSFSA-M 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- YHGNXQAFNHCBTK-OWOJBTEDSA-N trans-3-hexenedioic acid Chemical compound OC(=O)C\C=C\CC(O)=O YHGNXQAFNHCBTK-OWOJBTEDSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Images
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
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/26—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group
- C07D501/28—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group with the 7-amino radical acylated by an aliphatic carboxylic acid, which is substituted by hetero atoms
-
- 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
-
- 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
-
- 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
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/26—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Cephalosporin Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (11)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03076636.4 | 2003-05-28 | ||
EP03076636 | 2003-05-28 | ||
PCT/NL2004/000367 WO2004106347A1 (en) | 2003-05-28 | 2004-05-24 | Cephem compound |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1795197A true CN1795197A (zh) | 2006-06-28 |
CN1795197B CN1795197B (zh) | 2010-06-02 |
Family
ID=33483955
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2004800146370A Expired - Fee Related CN1795197B (zh) | 2003-05-28 | 2004-05-24 | 头孢菌素类化合物 |
Country Status (7)
Country | Link |
---|---|
US (1) | US20070093465A1 (zh) |
EP (1) | EP1658296B1 (zh) |
JP (1) | JP2006528970A (zh) |
KR (1) | KR20060061295A (zh) |
CN (1) | CN1795197B (zh) |
ES (1) | ES2400562T3 (zh) |
WO (1) | WO2004106347A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107525733A (zh) * | 2017-08-09 | 2017-12-29 | 中国石油化工股份有限公司 | 井口井下腐蚀速率关联模型算法及使用此算法的井下腐蚀速率在线监测方法 |
CN115838753A (zh) * | 2021-09-18 | 2023-03-24 | 中国科学院天津工业生物技术研究所 | 一种生产7-氨基去乙酰氧基头孢烷酸的方法 |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007073947A2 (en) | 2005-12-28 | 2007-07-05 | Dsm Ip Assets B.V. | Mutant type ii beta- lactam acylases |
EP1987041B1 (en) * | 2006-02-23 | 2013-05-22 | DSM Sinochem Pharmaceuticals Netherlands B.V. | Improved cephalosporin production |
EP2592149A1 (en) | 2007-03-21 | 2013-05-15 | DSM IP Assets B.V. | Improved method for homologous recombination |
WO2009113853A2 (en) | 2008-03-11 | 2009-09-17 | Dsm Ip Assets B.V. | Adipate (ester or thioester) synthesis |
EP2392649A3 (en) | 2008-08-05 | 2012-01-11 | DSM IP Assets B.V. | Adipoyl-7-ADCA producing strains |
CN102369290A (zh) | 2009-04-03 | 2012-03-07 | 帝斯曼知识产权资产管理有限公司 | 发酵工艺 |
CN103003439A (zh) | 2010-06-22 | 2013-03-27 | 中化帝斯曼制药有限公司荷兰公司 | 气泡发酵工艺 |
AU2011273351A1 (en) | 2010-07-01 | 2013-01-17 | Dsm Ip Assets B.V. | A method for the production of a compound of interest |
WO2015091455A1 (en) | 2013-12-17 | 2015-06-25 | Dpx Holdings B.V. | Bioreactor |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE754693A (fr) | 1969-08-12 | 1971-02-11 | Lilly Co Eli | Nouvel antibiotique et procede pour le preparer |
IL36281A (en) | 1970-03-13 | 1977-04-29 | Merck & Co Inc | History of cephalosporins, antibiotic mixtures that include them and the process for their preparation |
GB1425081A (en) | 1972-06-27 | 1976-02-18 | Fujisawa Pharmaceutical Co | Antibiotics ws-3442a, b,c,d and e and n-acyl derivatives thereof |
JPS5318595B2 (zh) | 1972-08-31 | 1978-06-15 | ||
US4014873A (en) * | 1973-05-03 | 1977-03-29 | Merck & Co., Inc. | Process for the production of 7-acylamidocephalosporins |
US3914158A (en) | 1973-06-06 | 1975-10-21 | Merck & Co Inc | Antibiotic production |
GB1576103A (en) | 1976-02-19 | 1980-10-01 | Glaxo Lab Ltd | Transcarbamoylase enzyme and its use in producing 3-carbamoyloxymethyl cephalosporin antibiotics |
US4892819A (en) * | 1985-11-25 | 1990-01-09 | Eli Lilly And Company | Recombinant DNA expression vectors and DNA compounds that encode isopenicillin N synthetase from penicillium chrysogenum |
US5070020A (en) | 1988-05-09 | 1991-12-03 | Eli Lilly And Company | Recombinant dna expression vectors and dna compounds that encode deacetoxycephalosporin c synthetase |
EP0351029B1 (en) | 1988-07-15 | 2002-03-06 | Genencor International, Inc. | Novel glucose isomerase enzymes and their use |
DE4121350A1 (de) | 1991-06-28 | 1993-01-14 | Witzenmann Metallschlauchfab | Agraffschlauch mit kreisquerschnitt fuer abgasleitungen von brennkraftmaschinen |
CZ288721B6 (cs) * | 1991-10-15 | 2001-08-15 | Dsm Gist B. V. | Biologický způsob výroby kyseliny 7-aminodeacetylcefalosporanové |
DE69432543T2 (de) | 1993-07-23 | 2003-12-24 | Dsm N.V., Te Heerlen | Selektionmarker-genfreie rekombinante Stämme: Verfahren zur ihrer Herstellung und die Verwendung dieser Stämme |
JPH09512170A (ja) | 1994-04-22 | 1997-12-09 | メルク エンド カンパニー インコーポレーテッド | セファマイシン生合成後期酵素コーディングdna |
AU6400098A (en) | 1997-02-20 | 1998-09-09 | Gist-Brocades B.V. | Fermentative production of valuable compounds on an industrial scale using chemically defined media |
-
2004
- 2004-05-24 ES ES04748601T patent/ES2400562T3/es not_active Expired - Lifetime
- 2004-05-24 EP EP04748601A patent/EP1658296B1/en not_active Expired - Lifetime
- 2004-05-24 WO PCT/NL2004/000367 patent/WO2004106347A1/en active Application Filing
- 2004-05-24 US US10/557,814 patent/US20070093465A1/en not_active Abandoned
- 2004-05-24 CN CN2004800146370A patent/CN1795197B/zh not_active Expired - Fee Related
- 2004-05-24 JP JP2006532131A patent/JP2006528970A/ja not_active Withdrawn
- 2004-05-24 KR KR1020057022720A patent/KR20060061295A/ko not_active Application Discontinuation
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107525733A (zh) * | 2017-08-09 | 2017-12-29 | 中国石油化工股份有限公司 | 井口井下腐蚀速率关联模型算法及使用此算法的井下腐蚀速率在线监测方法 |
CN115838753A (zh) * | 2021-09-18 | 2023-03-24 | 中国科学院天津工业生物技术研究所 | 一种生产7-氨基去乙酰氧基头孢烷酸的方法 |
Also Published As
Publication number | Publication date |
---|---|
JP2006528970A (ja) | 2006-12-28 |
WO2004106347A1 (en) | 2004-12-09 |
ES2400562T3 (es) | 2013-04-10 |
KR20060061295A (ko) | 2006-06-07 |
US20070093465A1 (en) | 2007-04-26 |
EP1658296A1 (en) | 2006-05-24 |
CN1795197B (zh) | 2010-06-02 |
EP1658296B1 (en) | 2012-12-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2230790C2 (ru) | Способ расширения 5-членного кольца соединения бета-лактама до 6-членного цефема | |
CN1022036C (zh) | 一种头孢菌素化合物的制备方法 | |
CN1024669C (zh) | 新头孢烯类化合物的制备方法 | |
US20080131925A1 (en) | Production of Beta-Lactams in Single Cells | |
CN1203274A (zh) | 用于发酵制备l-半胱氨酸、l-胱氨酸、n-乙酰丝氨酸或四氢噻唑衍生物的微生物和方法 | |
CN1795197A (zh) | 头孢菌素类化合物 | |
CN1021226C (zh) | 头孢菌素衍生物的制备方法 | |
JPH09503908A (ja) | 3‐(カルボキシエチルチオ)プロピオニル‐7‐adcaを経由した7‐adcaの効果的な製造法 | |
CN1539983A (zh) | L-甲硫氨酸的发酵制造方法 | |
CN1781916A (zh) | 交联的糖肽-头孢菌素抗生素 | |
CN1062903C (zh) | 一种新的头孢菌素c酰基转移酶 | |
CN1531539A (zh) | 用α-酮酸衍生物制备头孢烷酸衍生物的酶促方法 | |
CN86100820A (zh) | 新头孢菌素的制备方法及其应用 | |
CN1015262B (zh) | 制备β-内酰胺类抗生素的方法 | |
CN1034578A (zh) | 编码构巢曲霉中异青霉素n合成酶的重组dna表达载体和dna化合物 | |
CN1226932A (zh) | 使编码乙酸苯酯分解代谢酶的基因失活的方法和质粒以及用其转化的菌株 | |
CN85106733A (zh) | 新头孢菌素化合物的制备方法 | |
US6468781B1 (en) | Stereoselective reductive amination of ketones | |
CN1681840A (zh) | 参与钴胺素生物合成的基因的转录活化基因 | |
CN1257269C (zh) | 一种生产7-氨基头孢烷酸的方法及其专用重组酶 | |
US8003358B2 (en) | Two-step enzyme method for preparing 7-aminocephalosporanic acid | |
CN1028236C (zh) | 酰基衍生物的制备方法 | |
CN1300290A (zh) | 新的头孢菌素化合物,其制备方法及含有它们的抗菌组合物 | |
CN1073444A (zh) | 头孢菌素类化合物及其制备方法 | |
CN85105299A (zh) | 头孢烯化合物的制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: NETHERLANDS COMPANY OF DSM SINOCHEM PHARMACEUTICAL Free format text: FORMER OWNER: DSM IP ASSETS BV Effective date: 20120329 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20120329 Address after: About Holland Patentee after: DSM SINOCHEM PHARMACEUTICALS NETHERLANDS B.V. Address before: Holland Heerlen Patentee before: DSM IP ASSETS B.V. |
|
CP01 | Change in the name or title of a patent holder | ||
CP01 | Change in the name or title of a patent holder |
Address after: About Holland Patentee after: DSM Sinochem Pharmaceuticals Netherlands B.V. Address before: About Holland Patentee before: DSM SINOCHEM PHARMACEUTICALS NETHERLANDS B.V. |
|
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20100602 Termination date: 20190524 |
|
CF01 | Termination of patent right due to non-payment of annual fee |