DE10234422A1 - Antibakterielle Ester-Makrozyklen - Google Patents

Info

Publication number

DE10234422A1

DE10234422A1 DE10234422A DE10234422A DE10234422A1 DE 10234422 A1 DE10234422 A1 DE 10234422A1 DE 10234422 A DE10234422 A DE 10234422A DE 10234422 A DE10234422 A DE 10234422A DE 10234422 A1 DE10234422 A1 DE 10234422A1

Authority

DE

Germany

Prior art keywords

alkyl

substituents

hydrogen

cycloalkyl

amino

Prior art date

2002-07-29

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Withdrawn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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• -1 ester macrocycles Chemical class 0.000 title claims description 218
• 230000000844 anti-bacterial effect Effects 0.000 title description 9
• 150000001875 compounds Chemical class 0.000 claims abstract description 115
• 238000000034 method Methods 0.000 claims abstract description 76
• 230000008569 process Effects 0.000 claims abstract description 21
• 238000002360 preparation method Methods 0.000 claims abstract description 14
• 238000011282 treatment Methods 0.000 claims abstract description 10
• 241001465754 Metazoa Species 0.000 claims abstract description 8
• 201000010099 disease Diseases 0.000 claims abstract description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
• 125000001424 substituent group Chemical group 0.000 claims description 75
• 229910052739 hydrogen Inorganic materials 0.000 claims description 73
• 239000001257 hydrogen Substances 0.000 claims description 73
• 125000000217 alkyl group Chemical group 0.000 claims description 69
• 125000000623 heterocyclic group Chemical group 0.000 claims description 62
• 229910052757 nitrogen Inorganic materials 0.000 claims description 41
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 36
• 125000001072 heteroaryl group Chemical group 0.000 claims description 36
• 150000002431 hydrogen Chemical class 0.000 claims description 36
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 35
• 125000003118 aryl group Chemical group 0.000 claims description 35
• 229910052736 halogen Inorganic materials 0.000 claims description 35
• 150000002367 halogens Chemical class 0.000 claims description 35
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 33
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 33
• 125000003545 alkoxy group Chemical group 0.000 claims description 32
• 125000003282 alkyl amino group Chemical group 0.000 claims description 32
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 31
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 30
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 25
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 23
• 150000001413 amino acids Chemical class 0.000 claims description 21
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 20
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 19
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 18
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 17
• 125000004432 carbon atom Chemical group C* 0.000 claims description 17
• 150000003839 salts Chemical class 0.000 claims description 17
• 125000000539 amino acid group Chemical group 0.000 claims description 16
• 125000003277 amino group Chemical group 0.000 claims description 16
• 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 14
• 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 14
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 12
• 208000035143 Bacterial infection Diseases 0.000 claims description 12
• 125000004391 aryl sulfonyl 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
• 125000003342 alkenyl group Chemical group 0.000 claims description 11
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
• 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 9
• 208000022362 bacterial infectious disease Diseases 0.000 claims description 8
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 8
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• 125000000304 alkynyl group Chemical group 0.000 claims description 6
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
• 125000005141 aryl amino sulfonyl group Chemical group 0.000 claims description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 3
• 238000006467 substitution reaction Methods 0.000 claims description 3
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
• 125000003974 3-carbamimidamidopropyl group Chemical group C(N)(=N)NCCC* 0.000 claims description 2
• 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 2
• 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 2
• 229940079593 drug Drugs 0.000 claims description 2
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 123
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 86
• 239000000243 solution Substances 0.000 description 76
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
• 239000000203 mixture Substances 0.000 description 52
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
• 239000002904 solvent Substances 0.000 description 39
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
• 238000006243 chemical reaction Methods 0.000 description 36
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 34
• 125000006239 protecting group Chemical group 0.000 description 34
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 29
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 28
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 239000003480 eluent Substances 0.000 description 21
• 238000005160 1H NMR spectroscopy Methods 0.000 description 20
• 229910052796 boron Inorganic materials 0.000 description 19
• 239000000047 product Substances 0.000 description 19
• 239000011541 reaction mixture Substances 0.000 description 19
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
• 229960001701 chloroform Drugs 0.000 description 18
• 238000004128 high performance liquid chromatography Methods 0.000 description 18
• 238000012360 testing method Methods 0.000 description 18
• 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 17
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
• 235000019253 formic acid Nutrition 0.000 description 17
• 238000003786 synthesis reaction Methods 0.000 description 17
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
• 239000012074 organic phase Substances 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
• 239000002585 base Substances 0.000 description 15
• 230000015572 biosynthetic process Effects 0.000 description 15
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 13
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 13
• 235000001014 amino acid Nutrition 0.000 description 13
• 229940024606 amino acid Drugs 0.000 description 13
• 230000008859 change Effects 0.000 description 13
• 239000003960 organic solvent Substances 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 229930195733 hydrocarbon Natural products 0.000 description 12
• 150000002430 hydrocarbons Chemical class 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• 229910052786 argon Inorganic materials 0.000 description 11
• 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 11
• 150000008282 halocarbons Chemical class 0.000 description 11
• 208000015181 infectious disease Diseases 0.000 description 11
• 229920006395 saturated elastomer Polymers 0.000 description 11
• 238000013519 translation Methods 0.000 description 11
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• 239000012043 crude product Substances 0.000 description 10
• 238000001972 liquid chromatography-electrospray ionisation mass spectrometry Methods 0.000 description 10
• 229910052938 sodium sulfate Inorganic materials 0.000 description 10
• 235000011152 sodium sulphate Nutrition 0.000 description 10
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
• 235000008206 alpha-amino acids Nutrition 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
• 125000005842 heteroatom Chemical group 0.000 description 9
• 238000000338 in vitro Methods 0.000 description 9
• 239000013612 plasmid Substances 0.000 description 9
• 239000011734 sodium Substances 0.000 description 9
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• 150000001371 alpha-amino acids Chemical class 0.000 description 8
• 239000000872 buffer Substances 0.000 description 8
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
• 239000000284 extract Substances 0.000 description 8
• 125000001181 organosilyl group Chemical group [SiH3]* 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
• 0 *C(*)N(*)C=C* Chemical compound *C(*)N(*)C=C* 0.000 description 7
• PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 7
• 241000588724 Escherichia coli Species 0.000 description 7
• 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 7
• 230000004913 activation Effects 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• 235000011181 potassium carbonates Nutrition 0.000 description 7
• 150000003254 radicals Chemical class 0.000 description 7
• 239000000741 silica gel Substances 0.000 description 7
• 229910002027 silica gel Inorganic materials 0.000 description 7
• 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 6
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
• 238000005481 NMR spectroscopy Methods 0.000 description 6
• 239000004793 Polystyrene Substances 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• 235000011054 acetic acid Nutrition 0.000 description 6
• 239000004480 active ingredient Substances 0.000 description 6
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
• 150000001718 carbodiimides Chemical class 0.000 description 6
• 238000010790 dilution Methods 0.000 description 6
• 239000012895 dilution Substances 0.000 description 6
• 238000002199 high-resolution Fourier transform ion cyclotron resonance mass spectrometry Methods 0.000 description 6
• 239000002609 medium Substances 0.000 description 6
• 244000052769 pathogen Species 0.000 description 6
• IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 6
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 6
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
• 230000014616 translation Effects 0.000 description 6
• LHFTUYBCCNRGQH-NRFANRHFSA-N (2s)-3-(5-iodo-2-phenylmethoxyphenyl)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC(I)=CC=C1OCC1=CC=CC=C1 LHFTUYBCCNRGQH-NRFANRHFSA-N 0.000 description 5
• 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 5
• 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 5
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 5
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
• 108090000331 Firefly luciferases Proteins 0.000 description 5
• 239000007821 HATU Substances 0.000 description 5
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
• 239000003513 alkali Substances 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 244000052616 bacterial pathogen Species 0.000 description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
• 229910000024 caesium carbonate Inorganic materials 0.000 description 5
• 150000001728 carbonyl compounds Chemical class 0.000 description 5
• 150000001735 carboxylic acids Chemical class 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
• 238000004440 column chromatography Methods 0.000 description 5
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
• 229920002223 polystyrene Polymers 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 229910000029 sodium carbonate Inorganic materials 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 5
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
• QLIBHSVXDAYYJR-UHFFFAOYSA-N 2-(bromomethyl)-4-iodo-1-phenylmethoxybenzene Chemical compound BrCC1=CC(I)=CC=C1OCC1=CC=CC=C1 QLIBHSVXDAYYJR-UHFFFAOYSA-N 0.000 description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
• IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 4
• CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 4
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
• BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 4
• DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
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