TWI277620B - Processes for preparation of 9,11-epoxy steroids and intermediates useful therein - Google Patents

Info

Publication number

TWI277620B

TWI277620B TW94131840A TW94131840A TWI277620B TW I277620 B TWI277620 B TW I277620B TW 94131840 A TW94131840 A TW 94131840A TW 94131840 A TW94131840 A TW 94131840A TW I277620 B TWI277620 B TW I277620B

Authority

TW

Taiwan

Prior art keywords

group

formula

compound

hydrogen

alkyl

Prior art date

1997-06-11

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 241
• 238000002360 preparation method Methods 0.000 title claims description 43
• 239000000543 intermediate Substances 0.000 title abstract description 100
• 230000008569 process Effects 0.000 title description 90
• 150000003431 steroids Chemical class 0.000 title description 24
• 239000004593 Epoxy Substances 0.000 title description 23
• 150000001875 compounds Chemical class 0.000 claims abstract description 638
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 273
• 239000001257 hydrogen Substances 0.000 claims abstract description 273
• 238000006243 chemical reaction Methods 0.000 claims abstract description 235
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 231
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 179
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 159
• 125000004104 aryloxy group Chemical group 0.000 claims abstract description 145
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 135
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims abstract description 126
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 116
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 89
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 74
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 52
• 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 43
• 230000015572 biosynthetic process Effects 0.000 claims abstract description 40
• -1 alkane Oxyalkyl Chemical group 0.000 claims description 192
• 150000002431 hydrogen Chemical class 0.000 claims description 176
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 121
• 239000002253 acid Substances 0.000 claims description 111
• 239000000047 product Substances 0.000 claims description 108
• 229910052736 halogen Inorganic materials 0.000 claims description 102
• 150000002367 halogens Chemical class 0.000 claims description 100
• 239000002904 solvent Substances 0.000 claims description 88
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 82
• 238000000855 fermentation Methods 0.000 claims description 74
• 230000004151 fermentation Effects 0.000 claims description 73
• 229910052799 carbon Inorganic materials 0.000 claims description 72
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 60
• 125000005843 halogen group Chemical group 0.000 claims description 60
• 239000002585 base Substances 0.000 claims description 57
• 229910001868 water Inorganic materials 0.000 claims description 56
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 54
• 125000000468 ketone group Chemical group 0.000 claims description 44
• 229910052783 alkali metal Inorganic materials 0.000 claims description 43
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 41
• 239000003153 chemical reaction reagent Substances 0.000 claims description 41
• 239000000758 substrate Substances 0.000 claims description 41
• 150000002576 ketones Chemical group 0.000 claims description 40
• 229910052760 oxygen Inorganic materials 0.000 claims description 39
• 239000001301 oxygen Substances 0.000 claims description 39
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 37
• 125000006612 decyloxy group Chemical group 0.000 claims description 36
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 35
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 34
• 239000002609 medium Substances 0.000 claims description 33
• YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 32
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 31
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
• 238000004519 manufacturing process Methods 0.000 claims description 30
• 150000003839 salts Chemical class 0.000 claims description 30
• 125000005429 oxyalkyl group Chemical group 0.000 claims description 28
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 27
• 150000002596 lactones Chemical class 0.000 claims description 26
• 241000237858 Gastropoda Species 0.000 claims description 24
• 150000002148 esters Chemical class 0.000 claims description 24
• 239000003960 organic solvent Substances 0.000 claims description 24
• 238000000605 extraction Methods 0.000 claims description 23
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 238000007254 oxidation reaction Methods 0.000 claims description 21
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 20
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
• 239000007789 gas Substances 0.000 claims description 19
• 125000001424 substituent group Chemical class 0.000 claims description 19
• 239000003795 chemical substances by application Substances 0.000 claims description 18
• 230000003647 oxidation Effects 0.000 claims description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims description 16
• 125000003118 aryl group Chemical group 0.000 claims description 15
• 238000005805 hydroxylation reaction Methods 0.000 claims description 15
• 150000002923 oximes Chemical class 0.000 claims description 14
• 238000012360 testing method Methods 0.000 claims description 14
• 244000005700 microbiome Species 0.000 claims description 13
• 230000000694 effects Effects 0.000 claims description 12
• 238000003379 elimination reaction Methods 0.000 claims description 12
• 238000005406 washing Methods 0.000 claims description 12
• 125000005055 alkyl alkoxy group Chemical group 0.000 claims description 11
• 229910052751 metal Inorganic materials 0.000 claims description 11
• 239000002184 metal Substances 0.000 claims description 11
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 10
• 239000006227 byproduct Substances 0.000 claims description 10
• 239000012535 impurity Substances 0.000 claims description 10
• 229910052707 ruthenium Inorganic materials 0.000 claims description 10
• 239000000126 substance Substances 0.000 claims description 10
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 9
• 230000008030 elimination Effects 0.000 claims description 9
• 150000001340 alkali metals Chemical class 0.000 claims description 8
• 238000006356 dehydrogenation reaction Methods 0.000 claims description 8
• 150000004820 halides Chemical class 0.000 claims description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 125000006239 protecting group Chemical group 0.000 claims description 7
• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
• 125000004122 cyclic group Chemical group 0.000 claims description 6
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 6
• 125000000457 gamma-lactone group Chemical group 0.000 claims description 6
• 150000002978 peroxides Chemical class 0.000 claims description 6
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
• 230000002378 acidificating effect Effects 0.000 claims description 5
• 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 5
• 230000003301 hydrolyzing effect Effects 0.000 claims description 5
• 150000002500 ions Chemical class 0.000 claims description 5
• 239000007800 oxidant agent Substances 0.000 claims description 5
• 239000004575 stone Substances 0.000 claims description 5
• 239000005864 Sulphur Substances 0.000 claims description 4
• 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 4
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 4
• 150000002825 nitriles Chemical class 0.000 claims description 4
• 150000003254 radicals Chemical class 0.000 claims description 4
• 239000011347 resin Substances 0.000 claims description 4
• 229920005989 resin Polymers 0.000 claims description 4
• 239000002168 alkylating agent Substances 0.000 claims description 3
• 229940100198 alkylating agent Drugs 0.000 claims description 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
• 150000001768 cations Chemical class 0.000 claims description 3
• JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical group N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 claims description 3
• 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 3
• 238000010025 steaming Methods 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical group O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 2
• 244000025254 Cannabis sativa Species 0.000 claims description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 claims description 2
• 239000003377 acid catalyst Substances 0.000 claims description 2
• 150000008052 alkyl sulfonates Chemical class 0.000 claims description 2
• 229960005286 carbaryl Drugs 0.000 claims description 2
• CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical group C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 claims description 2
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
• 238000006266 etherification reaction Methods 0.000 claims description 2
• 125000001188 haloalkyl group Chemical group 0.000 claims description 2
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 2
• 239000010977 jade Substances 0.000 claims description 2
• 229910044991 metal oxide Inorganic materials 0.000 claims description 2
• 150000004706 metal oxides Chemical class 0.000 claims description 2
• 150000004702 methyl esters Chemical class 0.000 claims description 2
• 239000002516 radical scavenger Substances 0.000 claims description 2
• 150000003573 thiols Chemical class 0.000 claims 12
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 10
• 125000005188 oxoalkyl group Chemical group 0.000 claims 7
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims 4
• QSJNAFJALFWFMT-UHFFFAOYSA-N meridine Chemical compound N1C=CC(=O)C2=C1C(=O)C1=NC=CC3=C(C=CC=C4)C4=NC2=C13 QSJNAFJALFWFMT-UHFFFAOYSA-N 0.000 claims 4
• 241000587155 Athene Species 0.000 claims 3
• 125000003710 aryl alkyl group Chemical group 0.000 claims 3
• AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical group [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 claims 3
• 230000001590 oxidative effect Effects 0.000 claims 3
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 3
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
• 125000000466 oxiranyl group Chemical group 0.000 claims 2
• 229910052727 yttrium Inorganic materials 0.000 claims 2
• SCBKKGZZWVHHOC-UHFFFAOYSA-N 2,2-bis(sulfanyl)propanoic acid Chemical compound CC(S)(S)C(O)=O SCBKKGZZWVHHOC-UHFFFAOYSA-N 0.000 claims 1
• ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims 1
• XGLOTIMKDGLOKV-UHFFFAOYSA-N C1=CC=CC=2C3=CC=CC=C3CC12.[C] Chemical group C1=CC=CC=2C3=CC=CC=C3CC12.[C] XGLOTIMKDGLOKV-UHFFFAOYSA-N 0.000 claims 1
• 208000001613 Gambling Diseases 0.000 claims 1
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 1
• PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 claims 1
• PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Natural products C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 1
• YGMJSOJKDUHWCY-UHFFFAOYSA-N [C].N1C=CC=CC=C1 Chemical compound [C].N1C=CC=CC=C1 YGMJSOJKDUHWCY-UHFFFAOYSA-N 0.000 claims 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
• 229910001508 alkali metal halide Inorganic materials 0.000 claims 1
• 150000008045 alkali metal halides Chemical class 0.000 claims 1
• 229930013930 alkaloid Natural products 0.000 claims 1
• 150000003797 alkaloid derivatives Chemical class 0.000 claims 1
• 125000005256 alkoxyacyl group Chemical group 0.000 claims 1
• 230000002152 alkylating effect Effects 0.000 claims 1
• 125000005577 anthracene group Chemical group 0.000 claims 1
• 125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
• 125000001309 chloro group Chemical group Cl* 0.000 claims 1
• 229940125898 compound 5 Drugs 0.000 claims 1
• 238000005336 cracking Methods 0.000 claims 1
• YZLDHQLGRXYVPY-UHFFFAOYSA-N decyl cyanate Chemical compound CCCCCCCCCCOC#N YZLDHQLGRXYVPY-UHFFFAOYSA-N 0.000 claims 1
• 238000004200 deflagration Methods 0.000 claims 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
• RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 claims 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 claims 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims 1
• 239000010931 gold Substances 0.000 claims 1
• 229910052737 gold Inorganic materials 0.000 claims 1
• 125000005842 heteroatom Chemical group 0.000 claims 1
• JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims 1
• 238000006146 oximation reaction Methods 0.000 claims 1
• JIWAALDUIFCBLV-UHFFFAOYSA-N oxoosmium Chemical compound [Os]=O JIWAALDUIFCBLV-UHFFFAOYSA-N 0.000 claims 1
• YHYZBEAWTMHNAI-UHFFFAOYSA-N phenanthrene-4-carbonitrile Chemical compound C1=CC=CC2=C3C(C#N)=CC=CC3=CC=C21 YHYZBEAWTMHNAI-UHFFFAOYSA-N 0.000 claims 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
• 238000007363 ring formation reaction Methods 0.000 claims 1
• UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 claims 1
• 229910001428 transition metal ion Inorganic materials 0.000 claims 1
• 238000003786 synthesis reaction Methods 0.000 abstract description 21
• JUKPWJGBANNWMW-VWBFHTRKSA-N eplerenone Chemical compound C([C@@H]1[C@]2(C)C[C@H]3O[C@]33[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)C(=O)OC)C[C@@]21CCC(=O)O1 JUKPWJGBANNWMW-VWBFHTRKSA-N 0.000 abstract description 3
• 229960001208 eplerenone Drugs 0.000 abstract description 3
• 125000001475 halogen functional group Chemical group 0.000 abstract 3
• 125000002252 acyl group Chemical group 0.000 abstract 2
• 125000005041 acyloxyalkyl group Chemical group 0.000 abstract 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
• 239000000243 solution Substances 0.000 description 115
• 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 60
• 239000008103 glucose Substances 0.000 description 60
• 239000000203 mixture Substances 0.000 description 60
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 40
• 239000000725 suspension Substances 0.000 description 37
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 32
• 230000036983 biotransformation Effects 0.000 description 28
• 239000011541 reaction mixture Substances 0.000 description 28
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 27
• 125000005594 diketone group Chemical group 0.000 description 27
• 235000015097 nutrients Nutrition 0.000 description 26
• 235000018102 proteins Nutrition 0.000 description 24
• 102000004169 proteins and genes Human genes 0.000 description 24
• 108090000623 proteins and genes Proteins 0.000 description 24
• 229940041514 candida albicans extract Drugs 0.000 description 23
• 239000012138 yeast extract Substances 0.000 description 23
• 210000004907 gland Anatomy 0.000 description 22
• 239000001963 growth medium Substances 0.000 description 22
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 22
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 20
• 238000007792 addition Methods 0.000 description 20
• 238000006735 epoxidation reaction Methods 0.000 description 20
• 210000004215 spore Anatomy 0.000 description 20
• 235000019441 ethanol Nutrition 0.000 description 19
• 230000012010 growth Effects 0.000 description 19
• 230000007062 hydrolysis Effects 0.000 description 19
• 238000006460 hydrolysis reaction Methods 0.000 description 19
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
• 239000000052 vinegar Substances 0.000 description 18
• 235000021419 vinegar Nutrition 0.000 description 18
• 235000019439 ethyl acetate Nutrition 0.000 description 17
• 238000001914 filtration Methods 0.000 description 17
• 229920001817 Agar Polymers 0.000 description 16
• 239000008272 agar Substances 0.000 description 16
• 230000001954 sterilising effect Effects 0.000 description 16
• 238000004659 sterilization and disinfection Methods 0.000 description 16
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 150000002081 enamines Chemical class 0.000 description 15
• 239000002054 inoculum Substances 0.000 description 15
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
• 239000012043 crude product Substances 0.000 description 14
• 239000007787 solid Substances 0.000 description 14
• 235000013339 cereals Nutrition 0.000 description 13
• 239000000284 extract Substances 0.000 description 13
• 239000007788 liquid Substances 0.000 description 13
• 239000012071 phase Substances 0.000 description 13
• 239000002689 soil Substances 0.000 description 13
• 210000001519 tissue Anatomy 0.000 description 13
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
• 238000013019 agitation Methods 0.000 description 12
• 150000001336 alkenes Chemical class 0.000 description 12
• 230000008901 benefit Effects 0.000 description 12
• 235000019253 formic acid Nutrition 0.000 description 12
• 230000002829 reductive effect Effects 0.000 description 12
• 238000011218 seed culture Methods 0.000 description 12
• 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 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 11
• 239000012190 activator Substances 0.000 description 11
• 239000008367 deionised water Substances 0.000 description 11
• 229910021641 deionized water Inorganic materials 0.000 description 11
• 239000012153 distilled water Substances 0.000 description 11
• 238000005470 impregnation Methods 0.000 description 11
• 235000011054 acetic acid Nutrition 0.000 description 10
• 150000004703 alkoxides Chemical class 0.000 description 10
• 239000003242 anti bacterial agent Substances 0.000 description 10
• 239000012984 antibiotic solution Substances 0.000 description 10
• 238000004587 chromatography analysis Methods 0.000 description 10
• 235000013882 gravy Nutrition 0.000 description 10
• 150000002924 oxiranes Chemical class 0.000 description 10
• 238000011282 treatment Methods 0.000 description 10
• 239000004254 Ammonium phosphate Substances 0.000 description 9
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 9
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
• 235000019289 ammonium phosphates Nutrition 0.000 description 9
• 229940088710 antibiotic agent Drugs 0.000 description 9
• 210000004027 cell Anatomy 0.000 description 9
• 238000011084 recovery Methods 0.000 description 9
• 238000012546 transfer Methods 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• 150000001241 acetals Chemical class 0.000 description 8
• 229910000148 ammonium phosphate Inorganic materials 0.000 description 8
• 238000007333 cyanation reaction Methods 0.000 description 8
• MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 8
• 230000001965 increasing effect Effects 0.000 description 8
• 229910052500 inorganic mineral Inorganic materials 0.000 description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
• 235000010755 mineral Nutrition 0.000 description 8
• 239000011707 mineral Substances 0.000 description 8
• 230000035484 reaction time Effects 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• 230000009466 transformation Effects 0.000 description 8
• 240000006439 Aspergillus oryzae Species 0.000 description 7
• 235000002247 Aspergillus oryzae Nutrition 0.000 description 7
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 7
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 7
• 239000000654 additive Substances 0.000 description 7
• 239000002518 antifoaming agent Substances 0.000 description 7
• 230000009286 beneficial effect Effects 0.000 description 7
• 239000002274 desiccant Substances 0.000 description 7
• 238000004821 distillation Methods 0.000 description 7
• 239000002245 particle Substances 0.000 description 7
• 229910052698 phosphorus Inorganic materials 0.000 description 7
• 239000011574 phosphorus Substances 0.000 description 7
• HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• 229920000858 Cyclodextrin Polymers 0.000 description 6
• 206010036790 Productive cough Diseases 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• 240000005384 Rhizopus oryzae Species 0.000 description 6
• 235000013752 Rhizopus oryzae Nutrition 0.000 description 6
• 239000003513 alkali Substances 0.000 description 6
• 150000001412 amines Chemical class 0.000 description 6
• AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 6
• 239000008346 aqueous phase Substances 0.000 description 6
• 238000001035 drying Methods 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 210000003802 sputum Anatomy 0.000 description 6
• 208000024794 sputum Diseases 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• 238000004809 thin layer chromatography Methods 0.000 description 6
• 241000223221 Fusarium oxysporum Species 0.000 description 5
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
• 229930182558 Sterol Natural products 0.000 description 5
• 230000000996 additive effect Effects 0.000 description 5
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 5
• 150000001413 amino acids Chemical class 0.000 description 5
• 229960005471 androstenedione Drugs 0.000 description 5
• AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 description 5
• 230000031709 bromination Effects 0.000 description 5
• 238000005893 bromination reaction Methods 0.000 description 5
• 239000007795 chemical reaction product Substances 0.000 description 5
• 239000007810 chemical reaction solvent Substances 0.000 description 5
• 239000000306 component Substances 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• 238000002425 crystallisation Methods 0.000 description 5
• 230000008025 crystallization Effects 0.000 description 5
• 238000010790 dilution Methods 0.000 description 5
• 239000012895 dilution Substances 0.000 description 5
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 5
• 125000004494 ethyl ester group Chemical group 0.000 description 5
• 239000007791 liquid phase Substances 0.000 description 5
• 238000002156 mixing Methods 0.000 description 5
• 230000001681 protective effect Effects 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 230000002441 reversible effect Effects 0.000 description 5
• 238000000926 separation method Methods 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 235000003702 sterols Nutrition 0.000 description 5
• VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 241001225321 Aspergillus fumigatus Species 0.000 description 4
• 241000228245 Aspergillus niger Species 0.000 description 4
• 235000010469 Glycine max Nutrition 0.000 description 4
• 229910019142 PO4 Inorganic materials 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• 241001450870 Thamnostylum piriforme Species 0.000 description 4
• 239000003463 adsorbent Substances 0.000 description 4
• 238000005273 aeration Methods 0.000 description 4
• 239000003125 aqueous solvent Substances 0.000 description 4
• 229940091771 aspergillus fumigatus Drugs 0.000 description 4
• FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 4
• 239000007853 buffer solution Substances 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 238000005119 centrifugation Methods 0.000 description 4
• 229940113088 dimethylacetamide Drugs 0.000 description 4
• 238000006073 displacement reaction Methods 0.000 description 4
• 235000013312 flour Nutrition 0.000 description 4
• 150000004676 glycans Chemical class 0.000 description 4
• LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
• 150000007522 mineralic acids Chemical class 0.000 description 4
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 4
• 235000021317 phosphate Nutrition 0.000 description 4
• 235000011007 phosphoric acid Nutrition 0.000 description 4
• 229920001282 polysaccharide Polymers 0.000 description 4
• 239000005017 polysaccharide Substances 0.000 description 4
• 239000011591 potassium Substances 0.000 description 4
• 229960003975 potassium Drugs 0.000 description 4
• 229910052700 potassium Inorganic materials 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 238000001556 precipitation Methods 0.000 description 4
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 4
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
• 238000000638 solvent extraction Methods 0.000 description 4
• 229960002256 spironolactone Drugs 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
• UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
• 241000187654 Nocardia Species 0.000 description 3
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
• 238000010521 absorption reaction Methods 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 238000005054 agglomeration Methods 0.000 description 3
• 230000002776 aggregation Effects 0.000 description 3
• 239000002170 aldosterone antagonist Substances 0.000 description 3
• 229910000272 alkali metal oxide Inorganic materials 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 150000008064 anhydrides Chemical class 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 230000018044 dehydration Effects 0.000 description 3
• 238000006297 dehydration reaction Methods 0.000 description 3
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 3
• 230000008034 disappearance Effects 0.000 description 3
• 150000002084 enol ethers Chemical class 0.000 description 3
• 238000001704 evaporation Methods 0.000 description 3
• 238000011049 filling Methods 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 235000011187 glycerol Nutrition 0.000 description 3
• 230000026030 halogenation Effects 0.000 description 3
• 238000005658 halogenation reaction Methods 0.000 description 3
• 230000033444 hydroxylation Effects 0.000 description 3
• 238000007654 immersion Methods 0.000 description 3
• 238000001802 infusion Methods 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 238000011068 loading method Methods 0.000 description 3
• 239000006210 lotion Substances 0.000 description 3
• 239000006166 lysate Substances 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 229910001507 metal halide Inorganic materials 0.000 description 3
• 150000005309 metal halides Chemical class 0.000 description 3
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
• 235000016709 nutrition Nutrition 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 239000012074 organic phase Substances 0.000 description 3
• 230000020477 pH reduction Effects 0.000 description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
• 239000010452 phosphate Substances 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 239000001632 sodium acetate Substances 0.000 description 3
• 235000017281 sodium acetate Nutrition 0.000 description 3
• 239000012265 solid product Substances 0.000 description 3
• 239000008223 sterile water Substances 0.000 description 3
• 239000011550 stock solution Substances 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 238000005979 thermal decomposition reaction Methods 0.000 description 3
• 230000001131 transforming effect Effects 0.000 description 3
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 3
• GWHCXVQVJPWHRF-KTKRTIGZSA-N (15Z)-tetracosenoic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCCCC(O)=O GWHCXVQVJPWHRF-KTKRTIGZSA-N 0.000 description 2
• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 2
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• WSCUHXPGYUMQEX-KCZNZURUSA-N 11beta-hydroxyandrost-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 WSCUHXPGYUMQEX-KCZNZURUSA-N 0.000 description 2
• FZEAQJIXYCPBLD-UHFFFAOYSA-N 11beta-hydroxyandrostenedione Natural products C1C(=O)CCC2(C)C3C(O)CC(C)(C(CC4)=O)C4C3CCC21 FZEAQJIXYCPBLD-UHFFFAOYSA-N 0.000 description 2
• UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 description 2
• HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 description 2
• 241000235389 Absidia Species 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• 241000351920 Aspergillus nidulans Species 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• 241001302652 Bassiana Species 0.000 description 2
• 241000751139 Beauveria bassiana Species 0.000 description 2
• 239000002028 Biomass Substances 0.000 description 2
• 229930186147 Cephalosporin Natural products 0.000 description 2
• 241000123346 Chrysosporium Species 0.000 description 2
• 235000001258 Cinchona calisaya Nutrition 0.000 description 2
• 241000609455 Corynespora cassiicola Species 0.000 description 2
• 241001558166 Curvularia sp. Species 0.000 description 2
• GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• 241001492222 Epicoccum Species 0.000 description 2
• 241000233866 Fungi Species 0.000 description 2
• 241000223218 Fusarium Species 0.000 description 2
• 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 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 229930194542 Keto Natural products 0.000 description 2
• CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• XJXROGWVRIJYMO-SJDLZYGOSA-N Nervonic acid Natural products O=C(O)[C@@H](/C=C/CCCCCCCC)CCCCCCCCCCCC XJXROGWVRIJYMO-SJDLZYGOSA-N 0.000 description 2
• 229920001213 Polysorbate 20 Polymers 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 241000007008 Stachys grandidentata Species 0.000 description 2
• 241000215410 Trichothecium roseum Species 0.000 description 2
• MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 description 2
• 208000027418 Wounds and injury Diseases 0.000 description 2
• 230000001476 alcoholic effect Effects 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 150000003863 ammonium salts Chemical class 0.000 description 2
• 239000011260 aqueous acid Substances 0.000 description 2
• 239000012736 aqueous medium Substances 0.000 description 2
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 2
• 229940106164 cephalexin Drugs 0.000 description 2
• 229940124587 cephalosporin Drugs 0.000 description 2
• 150000001780 cephalosporins Chemical class 0.000 description 2
• XMEVHPAGJVLHIG-FMZCEJRJSA-N chembl454950 Chemical compound [Cl-].C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H]([NH+](C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O XMEVHPAGJVLHIG-FMZCEJRJSA-N 0.000 description 2
• 239000000460 chlorine Substances 0.000 description 2
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
• GWHCXVQVJPWHRF-UHFFFAOYSA-N cis-tetracosenoic acid Natural products CCCCCCCCC=CCCCCCCCCCCCCCC(O)=O GWHCXVQVJPWHRF-UHFFFAOYSA-N 0.000 description 2
• 239000012141 concentrate Substances 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 230000001186 cumulative effect Effects 0.000 description 2
• MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
• 230000002950 deficient Effects 0.000 description 2
• 239000012024 dehydrating agents‎ Substances 0.000 description 2
• 238000007269 dehydrobromination reaction Methods 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 239000003599 detergent Substances 0.000 description 2
• 238000007865 diluting Methods 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 150000002085 enols Chemical class 0.000 description 2
• 230000032050 esterification Effects 0.000 description 2
• 238000005886 esterification reaction Methods 0.000 description 2
• CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 2
• 238000005187 foaming Methods 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 239000001307 helium Substances 0.000 description 2
• 229910052734 helium Inorganic materials 0.000 description 2
• SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 2
• 150000002373 hemiacetals Chemical class 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• 150000002430 hydrocarbons Chemical class 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 201000006747 infectious mononucleosis Diseases 0.000 description 2
• 239000013067 intermediate product Substances 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 239000003456 ion exchange resin Substances 0.000 description 2
• 229920003303 ion-exchange polymer Polymers 0.000 description 2
• 239000010410 layer Substances 0.000 description 2
• AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
• 235000013372 meat Nutrition 0.000 description 2
• 239000012533 medium component Substances 0.000 description 2
• 239000002207 metabolite Substances 0.000 description 2
• 229910000000 metal hydroxide Inorganic materials 0.000 description 2
• 150000004692 metal hydroxides Chemical class 0.000 description 2
• 239000002736 nonionic surfactant Substances 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• OEOFQABUOAWYMP-UHFFFAOYSA-N oxiren-2-ol Chemical compound OC1=CO1 OEOFQABUOAWYMP-UHFFFAOYSA-N 0.000 description 2
• 150000004965 peroxy acids Chemical class 0.000 description 2
• 239000002798 polar solvent Substances 0.000 description 2
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
• 229920000053 polysorbate 80 Polymers 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 2
• BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 2
• 230000001376 precipitating effect Effects 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 229960000948 quinine Drugs 0.000 description 2
• 239000012429 reaction media Substances 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 230000008929 regeneration Effects 0.000 description 2
• 238000011069 regeneration method Methods 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 238000010008 shearing Methods 0.000 description 2
• 239000002002 slurry Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 229910001220 stainless steel Inorganic materials 0.000 description 2
• 239000010935 stainless steel Substances 0.000 description 2
• 239000008174 sterile solution Substances 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 230000000153 supplemental effect Effects 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• 229960004989 tetracycline hydrochloride Drugs 0.000 description 2
• 230000007704 transition Effects 0.000 description 2
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
• 238000009423 ventilation Methods 0.000 description 2
• UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
• WSVPFJBQFXKCNU-UHFFFAOYSA-N (2,3,4,5-tetrachlorophenyl)hydrazine Chemical compound NNC1=CC(Cl)=C(Cl)C(Cl)=C1Cl WSVPFJBQFXKCNU-UHFFFAOYSA-N 0.000 description 1
• SIOSKXVCLBLPGK-FDJRCERISA-N (8s,9s,10r,11r,13s,14s)-3-ethoxy-11-hydroxy-10,13-dimethyl-1,2,7,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-one Chemical compound C1[C@@H](O)[C@@H]2[C@](CCC(OCC)=C3)(C)C3=CC[C@H]2[C@@H]2CCC(=O)[C@]21C SIOSKXVCLBLPGK-FDJRCERISA-N 0.000 description 1
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 1
• IMSVBNQVZVQSND-UHFFFAOYSA-N 1,5-bis(sulfanyl)pentan-3-one Chemical compound SCCC(=O)CCS IMSVBNQVZVQSND-UHFFFAOYSA-N 0.000 description 1
• GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 description 1
• SKIDNYUZJPMKFC-UHFFFAOYSA-N 1-iododecane Chemical compound CCCCCCCCCCI SKIDNYUZJPMKFC-UHFFFAOYSA-N 0.000 description 1
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
• ZMIBIIAWFMCVFD-UHFFFAOYSA-N 2,2-difluoroacetamide Chemical compound NC(=O)C(F)F ZMIBIIAWFMCVFD-UHFFFAOYSA-N 0.000 description 1
• FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 1
• PHTJBUCAVSBDHM-UHFFFAOYSA-N 2-(2-sulfanylethylamino)ethanethiol Chemical compound SCCNCCS PHTJBUCAVSBDHM-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• CQWXKASOCUAEOW-UHFFFAOYSA-N 2-[2-(carboxymethoxy)ethoxy]acetic acid Chemical compound OC(=O)COCCOCC(O)=O CQWXKASOCUAEOW-UHFFFAOYSA-N 0.000 description 1
• GPLIMIJPIZGPIF-UHFFFAOYSA-N 2-hydroxy-1,4-benzoquinone Chemical compound OC1=CC(=O)C=CC1=O GPLIMIJPIZGPIF-UHFFFAOYSA-N 0.000 description 1
• VNJOEUSYAMPBAK-UHFFFAOYSA-N 2-methylbenzenesulfonic acid;hydrate Chemical compound O.CC1=CC=CC=C1S(O)(=O)=O VNJOEUSYAMPBAK-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 1
• KPRGOTLNGIBVFL-GINZOMEDSA-N 7-ketodehydroepiandrosterone Chemical group C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C(=O)C=C21 KPRGOTLNGIBVFL-GINZOMEDSA-N 0.000 description 1
• PQJUJGAVDBINPI-UHFFFAOYSA-N 9H-thioxanthene Chemical compound C1=CC=C2CC3=CC=CC=C3SC2=C1 PQJUJGAVDBINPI-UHFFFAOYSA-N 0.000 description 1
• 241000235390 Absidia glauca Species 0.000 description 1
• 241000186361 Actinobacteria <class> Species 0.000 description 1
• 244000293623 Alyxia cinerea Species 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 241000134991 Aspergillus flavipes Species 0.000 description 1
• 241000228197 Aspergillus flavus Species 0.000 description 1
• 241001480052 Aspergillus japonicus Species 0.000 description 1
• 241000122824 Aspergillus ochraceus Species 0.000 description 1
• 241000194107 Bacillus megaterium Species 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 241001674044 Blattodea Species 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 101000856746 Bos taurus Cytochrome c oxidase subunit 7A1, mitochondrial Proteins 0.000 description 1
• 240000001889 Brahea edulis Species 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• ZVSQISKHOJFJQN-UHFFFAOYSA-N C(C)(=O)N.C=C.C=C.C=C Chemical compound C(C)(=O)N.C=C.C=C.C=C ZVSQISKHOJFJQN-UHFFFAOYSA-N 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 241000958587 Canis aureus Species 0.000 description 1
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 241000589518 Comamonas testosteroni Species 0.000 description 1
• 241000186216 Corynebacterium Species 0.000 description 1
• 241000010216 Cunninghamella blakesleeana Species 0.000 description 1
• 241001290628 Cunninghamella echinulata Species 0.000 description 1
• 241000235556 Cunninghamella elegans Species 0.000 description 1
• 241000371652 Curvularia clavata Species 0.000 description 1
• 241000223211 Curvularia lunata Species 0.000 description 1
• 108010092160 Dactinomycin Proteins 0.000 description 1
• 241000156609 Dasymutilla occidentalis Species 0.000 description 1
• XMSXQFUHVRWGNA-UHFFFAOYSA-N Decamethylcyclopentasiloxane Chemical compound C[Si]1(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O1 XMSXQFUHVRWGNA-UHFFFAOYSA-N 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• 239000001116 FEMA 4028 Substances 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
• 229920002527 Glycogen Polymers 0.000 description 1
• 241000590002 Helicobacter pylori Species 0.000 description 1
• 241000223198 Humicola Species 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• 241000221929 Hypomyces Species 0.000 description 1
• 241000221930 Hypomyces chrysospermus Species 0.000 description 1
• 241000908271 Ilyonectria destructans Species 0.000 description 1
• HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• 241001305961 Lichtheimia hyalospora Species 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 241000219171 Malpighiales Species 0.000 description 1
• 229920000877 Melamine resin Polymers 0.000 description 1
• CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 241000235575 Mortierella Species 0.000 description 1
• 241000235395 Mucor Species 0.000 description 1
• 241000186365 Mycobacterium fortuitum Species 0.000 description 1
• 241000187488 Mycobacterium sp. Species 0.000 description 1
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
• LMRSEVSTKGLDNY-UHFFFAOYSA-N N1C(=O)NC=2N=CNC2C1=O.CC1=CC=CC=C1 Chemical compound N1C(=O)NC=2N=CNC2C1=O.CC1=CC=CC=C1 LMRSEVSTKGLDNY-UHFFFAOYSA-N 0.000 description 1
• 241000244206 Nematoda Species 0.000 description 1
• 244000227633 Ocotea pretiosa Species 0.000 description 1
• 235000004263 Ocotea pretiosa Nutrition 0.000 description 1
• 241000238413 Octopus Species 0.000 description 1
• 239000004100 Oxytetracycline Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• 241000203720 Pimelobacter simplex Species 0.000 description 1
• 241000305299 Pithomyces Species 0.000 description 1
• 241000720793 Pithomyces cynodontis Species 0.000 description 1
• 241000422921 Polycephalomyces sinensis Species 0.000 description 1
• 241000396922 Pontia daplidice Species 0.000 description 1
• 229940122767 Potassium sparing diuretic Drugs 0.000 description 1
• 241000589516 Pseudomonas Species 0.000 description 1
• 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
• QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
• 241000235527 Rhizopus Species 0.000 description 1
• 241000235546 Rhizopus stolonifer Species 0.000 description 1
• 241000316848 Rhodococcus <scale insect> Species 0.000 description 1
• 241000187693 Rhodococcus rhodochrous Species 0.000 description 1
• 241000187560 Saccharopolyspora Species 0.000 description 1
• 241000634742 Saccharopolyspora erythraea NRRL 2338 Species 0.000 description 1
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 108010085012 Steroid Receptors Proteins 0.000 description 1
• 241000187747 Streptomyces Species 0.000 description 1
• 241000187180 Streptomyces sp. Species 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 241000292547 Taraxacum minimum Species 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 239000004098 Tetracycline Substances 0.000 description 1
• 244000299461 Theobroma cacao Species 0.000 description 1
• 235000009470 Theobroma cacao Nutrition 0.000 description 1
• 241000631893 Tieghemella Species 0.000 description 1
• LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
• DRUIESSIVFYOMK-UHFFFAOYSA-N Trichloroacetonitrile Chemical compound ClC(Cl)(Cl)C#N DRUIESSIVFYOMK-UHFFFAOYSA-N 0.000 description 1
• 235000021307 Triticum Nutrition 0.000 description 1
• 244000098338 Triticum aestivum Species 0.000 description 1
• 241000306282 Umbelopsis isabellina Species 0.000 description 1
• 240000006365 Vitis vinifera Species 0.000 description 1
• 206010052428 Wound Diseases 0.000 description 1
• 241001660687 Xantho Species 0.000 description 1
• YRXRDCQCGIRWPX-UHFFFAOYSA-N [Cl-].[SH3+].CCCCCCCCCC Chemical compound [Cl-].[SH3+].CCCCCCCCCC YRXRDCQCGIRWPX-UHFFFAOYSA-N 0.000 description 1
• YKUNURMQWBKWKM-UHFFFAOYSA-N [Cs+].[O-2].[K+] Chemical compound [Cs+].[O-2].[K+] YKUNURMQWBKWKM-UHFFFAOYSA-N 0.000 description 1
• JGFFTJDJHXLDNJ-UHFFFAOYSA-L [O-]OOO[O-].[K+].[K+] Chemical compound [O-]OOO[O-].[K+].[K+] JGFFTJDJHXLDNJ-UHFFFAOYSA-L 0.000 description 1
• 150000008065 acid anhydrides Chemical class 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 229930183665 actinomycin Natural products 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 229940083712 aldosterone antagonist Drugs 0.000 description 1
• 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
• 150000008041 alkali metal carbonates Chemical class 0.000 description 1
• 150000001339 alkali metal compounds Chemical class 0.000 description 1
• 239000012670 alkaline solution Substances 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 150000001351 alkyl iodides Chemical class 0.000 description 1
• SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 description 1
• ZRIUUUJAJJNDSS-UHFFFAOYSA-N ammonium phosphates Chemical class [NH4+].[NH4+].[NH4+].[O-]P([O-])([O-])=O ZRIUUUJAJJNDSS-UHFFFAOYSA-N 0.000 description 1
• BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
• 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
• 239000001166 ammonium sulphate Substances 0.000 description 1
• 235000011130 ammonium sulphate Nutrition 0.000 description 1
• 239000003957 anion exchange resin Substances 0.000 description 1
• PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
• 230000002280 anti-androgenic effect Effects 0.000 description 1
• 239000000051 antiandrogen Substances 0.000 description 1
• 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 229910001570 bauxite Inorganic materials 0.000 description 1
• 235000015278 beef Nutrition 0.000 description 1
• MVIOINXPSFUJEN-UHFFFAOYSA-N benzenesulfonic acid;hydrate Chemical compound O.OS(=O)(=O)C1=CC=CC=C1 MVIOINXPSFUJEN-UHFFFAOYSA-N 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
• 229960004853 betadex Drugs 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 235000011089 carbon dioxide Nutrition 0.000 description 1
• 238000006473 carboxylation reaction Methods 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 239000003729 cation exchange resin Substances 0.000 description 1
• 230000001364 causal effect Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 229910000420 cerium oxide Inorganic materials 0.000 description 1
• 239000003610 charcoal Substances 0.000 description 1
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 230000007882 cirrhosis Effects 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 238000010549 co-Evaporation Methods 0.000 description 1
• 229940126214 compound 3 Drugs 0.000 description 1
• 230000003750 conditioning effect Effects 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 150000001923 cyclic compounds Chemical class 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 229940086555 cyclomethicone Drugs 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 238000006704 dehydrohalogenation reaction Methods 0.000 description 1
• 238000002242 deionisation method Methods 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 239000012973 diazabicyclooctane Substances 0.000 description 1
• 150000001991 dicarboxylic acids Chemical class 0.000 description 1
• 150000005690 diesters Chemical class 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 235000013399 edible fruits Nutrition 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 125000003700 epoxy group Chemical group 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• 239000012374 esterification agent Substances 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• QPMJENKZJUFOON-PLNGDYQASA-N ethyl (z)-3-chloro-2-cyano-4,4,4-trifluorobut-2-enoate Chemical compound CCOC(=O)C(\C#N)=C(/Cl)C(F)(F)F QPMJENKZJUFOON-PLNGDYQASA-N 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 239000010419 fine particle Substances 0.000 description 1
• 125000005567 fluorenylene group Chemical group 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Substances O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
• 150000004674 formic acids Chemical class 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 230000008570 general process Effects 0.000 description 1
• 125000004383 glucosinolate group Chemical group 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 229940096919 glycogen Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000002140 halogenating effect Effects 0.000 description 1
• 229940037467 helicobacter pylori Drugs 0.000 description 1
• 150000002391 heterocyclic compounds Chemical class 0.000 description 1
• 230000000887 hydrating effect Effects 0.000 description 1
• 230000036571 hydration Effects 0.000 description 1
• 238000006703 hydration reaction Methods 0.000 description 1
• 150000002429 hydrazines Chemical class 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 238000005647 hydrohalogenation reaction Methods 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 238000009655 industrial fermentation Methods 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 238000011081 inoculation Methods 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 238000006317 isomerization reaction Methods 0.000 description 1
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
• 239000005453 ketone based solvent Substances 0.000 description 1
• 210000003127 knee Anatomy 0.000 description 1
• 238000007273 lactonization reaction Methods 0.000 description 1
• 238000011866 long-term treatment Methods 0.000 description 1
• 238000000464 low-speed centrifugation Methods 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 238000011177 media preparation Methods 0.000 description 1
• JDSHMPZPIAZGSV-UHFFFAOYSA-N melamine Chemical compound NC1=NC(N)=NC(N)=N1 JDSHMPZPIAZGSV-UHFFFAOYSA-N 0.000 description 1
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
• 229910052753 mercury Inorganic materials 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 125000005395 methacrylic acid group Chemical group 0.000 description 1
• NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N methyl ethyl ketone Substances CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
• 230000000813 microbial effect Effects 0.000 description 1
• 230000000116 mitigating effect Effects 0.000 description 1
• 239000011259 mixed solution Substances 0.000 description 1
• 239000012046 mixed solvent Substances 0.000 description 1
• 235000013379 molasses Nutrition 0.000 description 1
• 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 1
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
• WZJSNDBOBAUAQL-UHFFFAOYSA-N n,2,2,2-tetrachloroacetamide Chemical compound ClNC(=O)C(Cl)(Cl)Cl WZJSNDBOBAUAQL-UHFFFAOYSA-N 0.000 description 1
• OOHAUGDGCWURIT-UHFFFAOYSA-N n,n-dipentylpentan-1-amine Chemical compound CCCCCN(CCCCC)CCCCC OOHAUGDGCWURIT-UHFFFAOYSA-N 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 230000000422 nocturnal effect Effects 0.000 description 1
• 230000006911 nucleation Effects 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 125000000962 organic group Chemical group 0.000 description 1
• 125000001477 organic nitrogen group Chemical group 0.000 description 1
• 238000006053 organic reaction Methods 0.000 description 1
• BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 description 1
• IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 1
• 229960000625 oxytetracycline Drugs 0.000 description 1
• 235000019366 oxytetracycline Nutrition 0.000 description 1
• 230000003071 parasitic effect Effects 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 238000009928 pasteurization Methods 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 238000005554 pickling Methods 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 235000011181 potassium carbonates Nutrition 0.000 description 1
• 229910000160 potassium phosphate Inorganic materials 0.000 description 1
• 235000011009 potassium phosphates Nutrition 0.000 description 1
• 239000003286 potassium sparing diuretic agent Substances 0.000 description 1
• 229940097241 potassium-sparing diuretic Drugs 0.000 description 1
• CASUWPDYGGAUQV-UHFFFAOYSA-M potassium;methanol;hydroxide Chemical compound [OH-].[K+].OC CASUWPDYGGAUQV-UHFFFAOYSA-M 0.000 description 1
• 238000007639 printing Methods 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 239000013587 production medium Substances 0.000 description 1
• SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
• 229960005385 proguanil Drugs 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 238000005086 pumping Methods 0.000 description 1
• 230000006340 racemization Effects 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 235000021283 resveratrol Nutrition 0.000 description 1
• 229940016667 resveratrol Drugs 0.000 description 1
• 229930002330 retinoic acid Natural products 0.000 description 1
• 238000007142 ring opening reaction Methods 0.000 description 1
• 239000012266 salt solution Substances 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 239000013049 sediment Substances 0.000 description 1
• 230000035040 seed growth Effects 0.000 description 1
• 238000010956 selective crystallization Methods 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 235000020183 skimmed milk Nutrition 0.000 description 1
• 239000002893 slag Substances 0.000 description 1
• 239000000779 smoke Substances 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 102000005969 steroid hormone receptors Human genes 0.000 description 1
• 150000003432 sterols Chemical class 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 229910052712 strontium Inorganic materials 0.000 description 1
• CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
• 238000006277 sulfonation reaction Methods 0.000 description 1
• 229910021653 sulphate ion Inorganic materials 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000007586 terpenes Nutrition 0.000 description 1
• IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 1
• 229960002180 tetracycline Drugs 0.000 description 1
• 235000019364 tetracycline Nutrition 0.000 description 1
• 229930101283 tetracycline Natural products 0.000 description 1
• 150000003522 tetracyclines Chemical class 0.000 description 1
• 125000003698 tetramethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical class SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 description 1
• XDLNRRRJZOJTRW-UHFFFAOYSA-N thiohypochlorous acid Chemical compound ClS XDLNRRRJZOJTRW-UHFFFAOYSA-N 0.000 description 1
• HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
• 230000008467 tissue growth Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• 229960001727 tretinoin Drugs 0.000 description 1
• 125000005270 trialkylamine group Chemical group 0.000 description 1
• CMMXCVYESRODNH-UHFFFAOYSA-N trichloroepoxyethane Chemical compound ClC1OC1(Cl)Cl CMMXCVYESRODNH-UHFFFAOYSA-N 0.000 description 1
• JFOWPZXGNKSOTH-UHFFFAOYSA-N tridecyl decanoate Chemical compound CCCCCCCCCCCCCOC(=O)CCCCCCCCC JFOWPZXGNKSOTH-UHFFFAOYSA-N 0.000 description 1
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
• IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 238000009834 vaporization Methods 0.000 description 1
• 230000008016 vaporization Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000010455 vermiculite Substances 0.000 description 1
• 229910052902 vermiculite Inorganic materials 0.000 description 1
• 235000019354 vermiculite Nutrition 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000000007 visual effect Effects 0.000 description 1
• 229930003231 vitamin Natural products 0.000 description 1
• 235000013343 vitamin Nutrition 0.000 description 1
• 239000011782 vitamin Substances 0.000 description 1
• 229940088594 vitamin Drugs 0.000 description 1