DE102005014240A1 - Antibakterielle Amid-Makrozyklen IV - Google Patents

Info

Publication number

DE102005014240A1

DE102005014240A1 DE102005014240A DE102005014240A DE102005014240A1 DE 102005014240 A1 DE102005014240 A1 DE 102005014240A1 DE 102005014240 A DE102005014240 A DE 102005014240A DE 102005014240 A DE102005014240 A DE 102005014240A DE 102005014240 A1 DE102005014240 A1 DE 102005014240A1

Authority

DE

Germany

Prior art keywords

amino

hydrogen

independently

mmol

tert

Prior art date

2004-09-24

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.)

Withdrawn

Links

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• 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 10
• -1 amide macrocycles Chemical class 0.000 title abstract description 103
• 238000000034 method Methods 0.000 claims abstract description 243
• 238000002360 preparation method Methods 0.000 claims abstract description 54
• 201000010099 disease Diseases 0.000 claims abstract description 17
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
• 238000011282 treatment Methods 0.000 claims abstract description 17
• 238000011321 prophylaxis Methods 0.000 claims abstract description 14
• 208000035143 Bacterial infection Diseases 0.000 claims abstract description 13
• 239000003814 drug Substances 0.000 claims abstract description 11
• 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 9
• 238000004519 manufacturing process Methods 0.000 claims abstract description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 249
• 229910052739 hydrogen Inorganic materials 0.000 claims description 232
• 239000001257 hydrogen Substances 0.000 claims description 232
• 150000001875 compounds Chemical class 0.000 claims description 210
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 134
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 127
• 150000002431 hydrogen Chemical class 0.000 claims description 106
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 105
• 229910052757 nitrogen Inorganic materials 0.000 claims description 98
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 97
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 93
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 92
• 229910052799 carbon Inorganic materials 0.000 claims description 64
• 150000003839 salts Chemical class 0.000 claims description 57
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 55
• 239000012453 solvate Substances 0.000 claims description 46
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 32
• 125000004193 piperazinyl group Chemical group 0.000 claims description 24
• 125000004432 carbon atom Chemical group C* 0.000 claims description 22
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
• 238000004587 chromatography analysis Methods 0.000 claims description 20
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
• 239000002253 acid Substances 0.000 claims description 13
• 239000003153 chemical reaction reagent Substances 0.000 claims description 7
• 238000007327 hydrogenolysis reaction Methods 0.000 claims description 7
• 241001465754 Metazoa Species 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 231100000252 nontoxic Toxicity 0.000 claims description 3
• 230000003000 nontoxic effect Effects 0.000 claims description 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 303
• 239000000243 solution Substances 0.000 description 286
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 221
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 207
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 183
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 176
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 156
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 153
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 150
• 239000000203 mixture Substances 0.000 description 89
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 87
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 80
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 80
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 76
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 73
• 239000003480 eluent Substances 0.000 description 71
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
• 239000012043 crude product Substances 0.000 description 68
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 66
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 64
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 63
• 238000006243 chemical reaction Methods 0.000 description 63
• 239000012074 organic phase Substances 0.000 description 62
• 239000007787 solid Substances 0.000 description 61
• 238000000746 purification Methods 0.000 description 60
• 238000005160 1H NMR spectroscopy Methods 0.000 description 59
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 58
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 57
• 239000011541 reaction mixture Substances 0.000 description 56
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 54
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 53
• WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 48
• 239000002904 solvent Substances 0.000 description 47
• 239000000047 product Substances 0.000 description 46
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 44
• 150000001721 carbon Chemical group 0.000 description 43
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 43
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 42
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 40
• 229910052786 argon Inorganic materials 0.000 description 40
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 40
• 235000019341 magnesium sulphate Nutrition 0.000 description 40
• 239000000706 filtrate Substances 0.000 description 39
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 38
• 235000019253 formic acid Nutrition 0.000 description 38
• 238000003756 stirring Methods 0.000 description 38
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 36
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 36
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
• 238000004128 high performance liquid chromatography Methods 0.000 description 35
• 238000002953 preparative HPLC Methods 0.000 description 34
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 34
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 33
• 229910052763 palladium Inorganic materials 0.000 description 33
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 33
• 239000011780 sodium chloride Substances 0.000 description 31
• 239000012071 phase Substances 0.000 description 30
• XZLRJCSXDLXBSC-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl 2-cyanoacetate Chemical group CC(C)(C)OC(=O)NCCCOC(=O)CC#N XZLRJCSXDLXBSC-UHFFFAOYSA-N 0.000 description 29
• 239000007821 HATU Substances 0.000 description 24
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 22
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 22
• 229960000583 acetic acid Drugs 0.000 description 22
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 21
• 239000002585 base Substances 0.000 description 20
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 19
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
• 229910052938 sodium sulfate Inorganic materials 0.000 description 18
• 235000011152 sodium sulphate Nutrition 0.000 description 18
• 238000012360 testing method Methods 0.000 description 18
• 239000005909 Kieselgur Substances 0.000 description 17
• 239000000741 silica gel Substances 0.000 description 17
• 229910002027 silica gel Inorganic materials 0.000 description 17
• 239000011734 sodium Substances 0.000 description 17
• IXCAVSIBYPQLGV-NSHDSACASA-N tert-butyl n-[(2s)-1-amino-5-[(2-methylpropan-2-yl)oxycarbonylamino]pentan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NCCC[C@@H](CN)NC(=O)OC(C)(C)C IXCAVSIBYPQLGV-NSHDSACASA-N 0.000 description 17
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 16
• 238000000825 ultraviolet detection Methods 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• 235000011054 acetic acid Nutrition 0.000 description 14
• 229960001701 chloroform Drugs 0.000 description 14
• WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 14
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 14
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 14
• 239000007858 starting material Substances 0.000 description 13
• 238000003786 synthesis reaction Methods 0.000 description 13
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
• 230000015572 biosynthetic process Effects 0.000 description 12
• 229920006395 saturated elastomer Polymers 0.000 description 12
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
• 208000015181 infectious disease Diseases 0.000 description 11
• 238000004007 reversed phase HPLC Methods 0.000 description 11
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 11
• 238000013519 translation Methods 0.000 description 11
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 10
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 10
• 238000010790 dilution Methods 0.000 description 10
• 239000012895 dilution Substances 0.000 description 10
• 238000000338 in vitro Methods 0.000 description 10
• QYYCZJUFHDLLOJ-AWEZNQCLSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CCCNC(=O)OCC1=CC=CC=C1 QYYCZJUFHDLLOJ-AWEZNQCLSA-N 0.000 description 9
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 239000002609 medium Substances 0.000 description 9
• 239000013612 plasmid Substances 0.000 description 9
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
• RWQCKACYKKSOKK-AWEZNQCLSA-N (2s)-5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound CC(C)(C)OC(=O)NCCC[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 RWQCKACYKKSOKK-AWEZNQCLSA-N 0.000 description 8
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 8
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
• 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 8
• 239000000284 extract Substances 0.000 description 8
• 239000012362 glacial acetic acid Substances 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• 241000588724 Escherichia coli Species 0.000 description 7
• 238000003556 assay Methods 0.000 description 7
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
• 229910000024 caesium carbonate Inorganic materials 0.000 description 7
• 229960003104 ornithine Drugs 0.000 description 7
• 235000011056 potassium acetate Nutrition 0.000 description 7
• 229910000029 sodium carbonate Inorganic materials 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• LZNOKWJGNPKUSE-UHFFFAOYSA-N tert-butyl n-(3-amino-2-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC(O)CN LZNOKWJGNPKUSE-UHFFFAOYSA-N 0.000 description 7
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 7
• 239000003643 water by type Substances 0.000 description 7
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
• ZVKUKBNZGQJCFJ-UHFFFAOYSA-N 2-aminoethyl(benzyl)carbamic acid;hydrochloride Chemical compound Cl.NCCN(C(O)=O)CC1=CC=CC=C1 ZVKUKBNZGQJCFJ-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• 229920001817 Agar Polymers 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• 241000894006 Bacteria Species 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 6
• 239000008272 agar Substances 0.000 description 6
• 108010046011 biphenomycin B Proteins 0.000 description 6
• OXLPMCIPYGNLJD-OWSLCNJRSA-N biphenomycin b Chemical compound C=1C2=CC=C(O)C=1C[C@@H](C(O)=O)NC(=O)[C@H](C[C@@H](O)CN)NC(=O)[C@@H](N)CC1=CC2=CC=C1O OXLPMCIPYGNLJD-OWSLCNJRSA-N 0.000 description 6
• 239000000872 buffer Substances 0.000 description 6
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 6
• 238000001035 drying Methods 0.000 description 6
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 6
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 6
• 229960004592 isopropanol Drugs 0.000 description 6
• 239000012280 lithium aluminium hydride Substances 0.000 description 6
• 244000052769 pathogen Species 0.000 description 6
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 5
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
• 108090000331 Firefly luciferases Proteins 0.000 description 5
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
• 239000007983 Tris buffer Substances 0.000 description 5
• AUBZNQJECNDZEK-BOXHHOBZSA-N [(3s)-6-amino-1-oxo-1-[2-(phenylmethoxycarbonylamino)ethylamino]hexan-3-yl]-benzylcarbamic acid;hydrochloride Chemical compound Cl.C([C@H](CCCN)N(CC=1C=CC=CC=1)C(O)=O)C(=O)NCCNC(=O)OCC1=CC=CC=C1 AUBZNQJECNDZEK-BOXHHOBZSA-N 0.000 description 5
• 150000007513 acids Chemical class 0.000 description 5
• 239000008346 aqueous phase Substances 0.000 description 5
• 239000012300 argon atmosphere Substances 0.000 description 5
• 230000001580 bacterial effect Effects 0.000 description 5
• SLMOCVXNGYHGJK-AWEZNQCLSA-N benzyl n-[(3s)-4-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CO)CCNC(=O)OCC1=CC=CC=C1 SLMOCVXNGYHGJK-AWEZNQCLSA-N 0.000 description 5
• 230000003115 biocidal effect Effects 0.000 description 5
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
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