KR20050010060A - 항균성 아미드 마크로사이클 - Google Patents

Info

Publication number

KR20050010060A

KR20050010060A KR10-2004-7020473A KR20047020473A KR20050010060A KR 20050010060 A KR20050010060 A KR 20050010060A KR 20047020473 A KR20047020473 A KR 20047020473A KR 20050010060 A KR20050010060 A KR 20050010060A

Authority

KR

South Korea

Prior art keywords

hydrogen

alkyl

substituents

amino

cycloalkyl

Prior art date

2002-06-17

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.)

Abandoned

Links

• Espacenet
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• -1 amide macrocycles Chemical class 0.000 title claims abstract description 248
• 230000000844 anti-bacterial effect Effects 0.000 title abstract 2
• 238000000034 method Methods 0.000 claims abstract description 144
• 208000035143 Bacterial infection Diseases 0.000 claims abstract description 14
• 238000011282 treatment Methods 0.000 claims abstract description 12
• 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 11
• 239000003814 drug Substances 0.000 claims abstract description 10
• 238000004519 manufacturing process Methods 0.000 claims abstract description 5
• 238000011321 prophylaxis Methods 0.000 claims abstract 2
• 150000001875 compounds Chemical class 0.000 claims description 153
• 229910052739 hydrogen Inorganic materials 0.000 claims description 131
• 239000001257 hydrogen Substances 0.000 claims description 131
• 125000001424 substituent group Chemical group 0.000 claims description 100
• 125000000217 alkyl group Chemical group 0.000 claims description 90
• 125000000623 heterocyclic group Chemical group 0.000 claims description 77
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 68
• 150000002431 hydrogen Chemical class 0.000 claims description 59
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 59
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 52
• 125000003118 aryl group Chemical group 0.000 claims description 51
• 229910052757 nitrogen Inorganic materials 0.000 claims description 51
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 48
• 125000001072 heteroaryl group Chemical group 0.000 claims description 47
• 125000003282 alkyl amino group Chemical group 0.000 claims description 39
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 38
• 229910052736 halogen Inorganic materials 0.000 claims description 36
• 150000002367 halogens Chemical class 0.000 claims description 36
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 35
• 125000003545 alkoxy group Chemical group 0.000 claims description 33
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 33
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 32
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 31
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 27
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 22
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 22
• 150000001413 amino acids Chemical class 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
• 150000003839 salts Chemical class 0.000 claims description 20
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 19
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 18
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
• 239000012453 solvate Substances 0.000 claims description 17
• 125000000539 amino acid group Chemical group 0.000 claims description 16
• 150000001412 amines Chemical class 0.000 claims description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
• 125000003342 alkenyl group Chemical group 0.000 claims description 12
• 125000003277 amino group Chemical group 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
• 230000000845 anti-microbial effect Effects 0.000 claims description 9
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 9
• 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 9
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 8
• 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 7
• 125000002757 morpholinyl group Chemical group 0.000 claims description 6
• 125000003386 piperidinyl group Chemical group 0.000 claims description 6
• 241001465754 Metazoa Species 0.000 claims description 5
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
• 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 4
• 201000010099 disease Diseases 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 3
• 125000000304 alkynyl group Chemical group 0.000 claims description 3
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
• 125000005141 aryl amino sulfonyl group Chemical group 0.000 claims description 3
• 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 3
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 3
• 230000002401 inhibitory effect Effects 0.000 claims description 3
• 230000002265 prevention Effects 0.000 claims description 3
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
• 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 2
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 2
• 239000004599 antimicrobial Substances 0.000 claims description 2
• GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims 1
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 153
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 142
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 120
• 239000000243 solution Substances 0.000 description 117
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 92
• 239000000203 mixture Substances 0.000 description 87
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 84
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 66
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 61
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
• 239000003480 eluent Substances 0.000 description 53
• 238000006243 chemical reaction Methods 0.000 description 52
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 45
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 42
• 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 42
• 235000019253 formic acid Nutrition 0.000 description 42
• 239000002904 solvent Substances 0.000 description 41
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 35
• 238000004128 high performance liquid chromatography Methods 0.000 description 35
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 32
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 31
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 30
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 30
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 27
• 239000012074 organic phase Substances 0.000 description 26
• 239000011541 reaction mixture Substances 0.000 description 26
• 238000003756 stirring Methods 0.000 description 26
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
• 229910052786 argon Inorganic materials 0.000 description 23
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 23
• 239000012043 crude product Substances 0.000 description 23
• 239000000047 product Substances 0.000 description 23
• 229960001701 chloroform Drugs 0.000 description 22
• 125000006239 protecting group Chemical group 0.000 description 22
• 125000004432 carbon atom Chemical group C* 0.000 description 20
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
• 239000012071 phase Substances 0.000 description 19
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 239000002585 base Substances 0.000 description 18
• 238000003786 synthesis reaction Methods 0.000 description 18
• 239000007821 HATU Substances 0.000 description 17
• 229910052938 sodium sulfate Inorganic materials 0.000 description 17
• 235000011152 sodium sulphate Nutrition 0.000 description 17
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 16
• 230000015572 biosynthetic process Effects 0.000 description 16
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 16
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 15
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 15
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
• 229940024606 amino acid Drugs 0.000 description 15
• 235000001014 amino acid Nutrition 0.000 description 15
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 15
• 238000000825 ultraviolet detection Methods 0.000 description 14
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
• 208000015181 infectious disease Diseases 0.000 description 13
• XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 12
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
• IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 12
• 238000012360 testing method Methods 0.000 description 12
• 238000013519 translation Methods 0.000 description 12
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 11
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 11
• 239000002253 acid Substances 0.000 description 11
• 230000008859 change Effects 0.000 description 11
• 239000003960 organic solvent Substances 0.000 description 11
• 229920006395 saturated elastomer Polymers 0.000 description 11
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 11
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
• 241000588724 Escherichia coli Species 0.000 description 10
• 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 description 10
• 125000005842 heteroatom Chemical group 0.000 description 10
• 229930195733 hydrocarbon Natural products 0.000 description 10
• 150000002430 hydrocarbons Chemical class 0.000 description 10
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 10
• 238000000746 purification Methods 0.000 description 10
• 150000003254 radicals Chemical class 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 9
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
• 150000005826 halohydrocarbons Chemical class 0.000 description 9
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
• 238000000338 in vitro Methods 0.000 description 9
• 239000013612 plasmid Substances 0.000 description 9
• 238000002360 preparation method Methods 0.000 description 9
• 239000003643 water by type Substances 0.000 description 9
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 8
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 235000008206 alpha-amino acids Nutrition 0.000 description 8
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
• 229910000024 caesium carbonate Inorganic materials 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• 239000000284 extract Substances 0.000 description 8
• 229960005190 phenylalanine Drugs 0.000 description 8
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
• 229910000027 potassium carbonate Inorganic materials 0.000 description 8
• 235000011181 potassium carbonates Nutrition 0.000 description 8
• 239000011780 sodium chloride Substances 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• 239000003826 tablet Substances 0.000 description 8
• UDSPRIUGJMVBTJ-MOPGFXCFSA-N (2s,4r)-4-[tert-butyl(dimethyl)silyl]oxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)C[C@@H](O[Si](C)(C)C(C)(C)C)CNC(=O)OCC1=CC=CC=C1 UDSPRIUGJMVBTJ-MOPGFXCFSA-N 0.000 description 7
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 7
• 229960000583 acetic acid Drugs 0.000 description 7
• 230000004913 activation Effects 0.000 description 7
• 150000001371 alpha-amino acids Chemical class 0.000 description 7
• 239000008346 aqueous phase Substances 0.000 description 7
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 238000002199 high-resolution Fourier transform ion cyclotron resonance mass spectrometry Methods 0.000 description 7
• 244000005700 microbiome Species 0.000 description 7
• 238000004007 reversed phase HPLC Methods 0.000 description 7
• 239000000741 silica gel Substances 0.000 description 7
• 229910002027 silica gel Inorganic materials 0.000 description 7
• 239000007787 solid Substances 0.000 description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
• XOSVVZQCJBMLPH-KRWDZBQOSA-N (2s)-3-(5-iodo-2-phenylmethoxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC(I)=CC=C1OCC1=CC=CC=C1 XOSVVZQCJBMLPH-KRWDZBQOSA-N 0.000 description 6
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 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 6
• 238000004458 analytical method Methods 0.000 description 6
• RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 239000013078 crystal 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
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
• 238000010898 silica gel chromatography Methods 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
• 229910000029 sodium carbonate Inorganic materials 0.000 description 6
• 235000017550 sodium carbonate Nutrition 0.000 description 6
• 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 6
• 230000014616 translation Effects 0.000 description 6
• DVPVLIJYSWYUBD-QRPNPIFTSA-N (2s)-2-(phenylmethoxycarbonylamino)propanoic acid;hydrochloride Chemical compound Cl.OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 DVPVLIJYSWYUBD-QRPNPIFTSA-N 0.000 description 5
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
• 238000005160 1H NMR spectroscopy Methods 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
• 241000607142 Salmonella Species 0.000 description 5
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