JP2008514561A - 抗菌性アミドマクロサイクルｉｖ - Google Patents

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Publication number

JP2008514561A

JP2008514561A JP2007532808A JP2007532808A JP2008514561A JP 2008514561 A JP2008514561 A JP 2008514561A JP 2007532808 A JP2007532808 A JP 2007532808A JP 2007532808 A JP2007532808 A JP 2007532808A JP 2008514561 A JP2008514561 A JP 2008514561A

Authority

JP

Japan

Prior art keywords

amino

independently

mmol

tert

represents hydrogen

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.)

Pending

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• -1 amide macrocycle Chemical class 0.000 title claims abstract description 102
• 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 12
• 238000000034 method Methods 0.000 claims abstract description 239
• 238000011282 treatment Methods 0.000 claims abstract description 14
• 201000010099 disease Diseases 0.000 claims abstract description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
• 208000035143 Bacterial infection Diseases 0.000 claims abstract description 11
• 239000003814 drug Substances 0.000 claims abstract description 11
• 238000004519 manufacturing process Methods 0.000 claims abstract description 11
• 230000006806 disease prevention Effects 0.000 claims abstract description 8
• 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 304
• 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 187
• 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 157
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 129
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 107
• 150000002431 hydrogen Chemical class 0.000 claims description 105
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 102
• 229910052757 nitrogen Inorganic materials 0.000 claims description 99
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 93
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 92
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 71
• 229910052799 carbon Inorganic materials 0.000 claims description 63
• 150000003839 salts Chemical class 0.000 claims description 48
• 239000012453 solvate Substances 0.000 claims description 45
• 238000002360 preparation method Methods 0.000 claims description 41
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 32
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
• 125000004193 piperazinyl group Chemical group 0.000 claims description 24
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
• 125000004432 carbon atom Chemical group C* 0.000 claims description 22
• 238000004587 chromatography analysis Methods 0.000 claims description 15
• 239000002253 acid Substances 0.000 claims description 14
• 230000008569 process Effects 0.000 claims description 13
• 239000003795 chemical substances by application Substances 0.000 claims description 9
• 238000007327 hydrogenolysis reaction Methods 0.000 claims description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• 231100000252 nontoxic Toxicity 0.000 claims description 3
• 230000003000 nontoxic effect Effects 0.000 claims description 3
• 241001465754 Metazoa Species 0.000 claims description 2
• 239000002671 adjuvant Substances 0.000 claims description 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 300
• 239000000243 solution Substances 0.000 description 274
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 207
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 205
• 239000000203 mixture Substances 0.000 description 199
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 177
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 175
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 155
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 153
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 150
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 115
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 97
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 96
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 86
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 82
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 81
• 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 76
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 72
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 70
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 70
• 239000012043 crude product Substances 0.000 description 69
• 238000006243 chemical reaction Methods 0.000 description 67
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
• 239000012074 organic phase Substances 0.000 description 62
• 238000000746 purification Methods 0.000 description 60
• 239000007787 solid Substances 0.000 description 60
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 55
• 239000011541 reaction mixture Substances 0.000 description 55
• 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
• 238000005160 1H NMR spectroscopy Methods 0.000 description 53
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 50
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 50
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 50
• 239000012071 phase Substances 0.000 description 50
• 239000002904 solvent Substances 0.000 description 47
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 44
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 44
• 229910052763 palladium Inorganic materials 0.000 description 44
• 238000003756 stirring Methods 0.000 description 44
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 44
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 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
• 150000001721 carbon Chemical group 0.000 description 42
• 239000003480 eluent Substances 0.000 description 42
• 229910052786 argon Inorganic materials 0.000 description 40
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
• 239000000706 filtrate Substances 0.000 description 39
• 239000000047 product Substances 0.000 description 39
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 38
• 235000019341 magnesium sulphate Nutrition 0.000 description 38
• NIPKDBBKUJDLHV-GGYWPGCISA-N tert-butyl N-[2-hydroxy-3-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(phenylmethoxycarbonylamino)butanoyl]amino]propyl]carbamate Chemical compound C(C1=CC=CC=C1)OC(NCC[C@@H](C(=O)NCC(CNC(=O)OC(C)(C)C)O)NC(=O)OC(C)(C)C)=O NIPKDBBKUJDLHV-GGYWPGCISA-N 0.000 description 38
• 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 36
• 235000019253 formic acid Nutrition 0.000 description 36
• 238000002953 preparative HPLC Methods 0.000 description 34
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 31
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 31
• 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
• 239000011780 sodium chloride Substances 0.000 description 24
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 22
• 229960000583 acetic acid Drugs 0.000 description 21
• 239000002585 base Substances 0.000 description 21
• 229960003104 ornithine Drugs 0.000 description 21
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 19
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 18
• 229910052938 sodium sulfate Inorganic materials 0.000 description 18
• 235000011152 sodium sulphate Nutrition 0.000 description 18
• 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
• 238000000825 ultraviolet detection Methods 0.000 description 17
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 16
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 16
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
• 229960001701 chloroform Drugs 0.000 description 14
• 238000010898 silica gel chromatography Methods 0.000 description 14
• 238000000967 suction filtration Methods 0.000 description 14
• 235000011054 acetic acid Nutrition 0.000 description 13
• 239000007858 starting material Substances 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
• 229920006395 saturated elastomer Polymers 0.000 description 12
• 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 12
• PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 11
• 230000015572 biosynthetic process Effects 0.000 description 11
• 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 11
• 238000001914 filtration Methods 0.000 description 11
• 238000004007 reversed phase HPLC Methods 0.000 description 11
• 238000003786 synthesis reaction Methods 0.000 description 11
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 10
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-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 compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 125000001841 imino group Chemical group [H]N=* 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
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 8
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 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
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 8
• 239000012362 glacial acetic acid Substances 0.000 description 8
• 125000001147 pentyl group Chemical group C(CCCC)* 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
• 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
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
• 238000005481 NMR spectroscopy 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
• 239000012141 concentrate Substances 0.000 description 7
• 238000010833 quantitative mass spectrometry Methods 0.000 description 7
• 239000000741 silica gel Substances 0.000 description 7
• 229910002027 silica gel Inorganic materials 0.000 description 7
• 229910000029 sodium carbonate Inorganic materials 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
• 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 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
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• 241000894006 Bacteria Species 0.000 description 6
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 6
• XNRHTMDHGDWBGP-UHFFFAOYSA-N carbamic acid;hydrochloride Chemical compound Cl.NC(O)=O XNRHTMDHGDWBGP-UHFFFAOYSA-N 0.000 description 6
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 6
• 239000012280 lithium aluminium hydride Substances 0.000 description 6
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-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
• 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
• 239000003054 catalyst Substances 0.000 description 5
• 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 5
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 5
• 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
• 238000002199 high-resolution Fourier transform ion cyclotron resonance mass spectrometry Methods 0.000 description 5
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 5
• 208000015181 infectious disease Diseases 0.000 description 5
• 239000012452 mother liquor Substances 0.000 description 5
• 229930014626 natural product Natural products 0.000 description 5
• 235000011056 potassium acetate Nutrition 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 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 4
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