CN103627744A - 一种酶催化合成2-取代苯并咪唑环类衍生物的方法 - Google Patents
一种酶催化合成2-取代苯并咪唑环类衍生物的方法 Download PDFInfo
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- CN103627744A CN103627744A CN201210376838.1A CN201210376838A CN103627744A CN 103627744 A CN103627744 A CN 103627744A CN 201210376838 A CN201210376838 A CN 201210376838A CN 103627744 A CN103627744 A CN 103627744A
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- lipase
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- 102000004190 Enzymes Human genes 0.000 title claims abstract description 22
- 108090000790 Enzymes Proteins 0.000 title claims abstract description 22
- 238000010189 synthetic method Methods 0.000 title claims abstract description 19
- 238000006555 catalytic reaction Methods 0.000 title claims abstract description 7
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 title abstract 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 102000004882 Lipase Human genes 0.000 claims abstract description 35
- 108090001060 Lipase Proteins 0.000 claims abstract description 35
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229940088598 enzyme Drugs 0.000 claims abstract description 21
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- 240000006439 Aspergillus oryzae Species 0.000 claims abstract description 10
- 235000002247 Aspergillus oryzae Nutrition 0.000 claims abstract description 10
- 102000004139 alpha-Amylases Human genes 0.000 claims abstract description 9
- 108090000637 alpha-Amylases Proteins 0.000 claims abstract description 9
- 229940024171 alpha-amylase Drugs 0.000 claims abstract description 9
- 102000013142 Amylases Human genes 0.000 claims abstract description 8
- 108010065511 Amylases Proteins 0.000 claims abstract description 8
- 210000000496 pancreas Anatomy 0.000 claims abstract description 8
- 239000000376 reactant Substances 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 67
- -1 2-substituted benzimidazole Chemical class 0.000 claims description 26
- 235000019441 ethanol Nutrition 0.000 claims description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 239000004382 Amylase Substances 0.000 claims description 5
- 235000019418 amylase Nutrition 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 101000693006 Sus scrofa Pancreatic alpha-amylase Proteins 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- 150000003577 thiophenes Chemical class 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 239000004367 Lipase Substances 0.000 abstract description 30
- 235000019421 lipase Nutrition 0.000 abstract description 30
- 238000000034 method Methods 0.000 abstract description 13
- 229940111205 diastase Drugs 0.000 abstract description 3
- 102000004142 Trypsin Human genes 0.000 abstract description 2
- 108090000631 Trypsin Proteins 0.000 abstract description 2
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 abstract 2
- 239000012588 trypsin Substances 0.000 abstract 1
- 239000012043 crude product Substances 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
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- 239000000047 product Substances 0.000 description 12
- 238000012512 characterization method Methods 0.000 description 11
- 230000009514 concussion Effects 0.000 description 11
- 238000001953 recrystallisation Methods 0.000 description 11
- 230000002194 synthesizing effect Effects 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 125000000068 chlorophenyl group Chemical group 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical compound C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 235000014493 Crataegus Nutrition 0.000 description 1
- 241001092040 Crataegus Species 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 229910021617 Indium monochloride Inorganic materials 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- APHGZSBLRQFRCA-UHFFFAOYSA-M indium(1+);chloride Chemical compound [In]Cl APHGZSBLRQFRCA-UHFFFAOYSA-M 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN104447697A (zh) * | 2014-11-24 | 2015-03-25 | 蚌埠丰原医药科技发展有限公司 | 一种达比加群酯中间体的制备方法 |
CN105483172A (zh) * | 2016-01-06 | 2016-04-13 | 西南大学 | α-猪胰淀粉酶在催化串联反应合成硝基环丙烷类化合物中的应用及方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102586356A (zh) * | 2011-12-29 | 2012-07-18 | 杭州师范大学 | 一种酶催化合成喹啉杂环衍生物的方法 |
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CN102586356A (zh) * | 2011-12-29 | 2012-07-18 | 杭州师范大学 | 一种酶催化合成喹啉杂环衍生物的方法 |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104447697A (zh) * | 2014-11-24 | 2015-03-25 | 蚌埠丰原医药科技发展有限公司 | 一种达比加群酯中间体的制备方法 |
CN105483172A (zh) * | 2016-01-06 | 2016-04-13 | 西南大学 | α-猪胰淀粉酶在催化串联反应合成硝基环丙烷类化合物中的应用及方法 |
CN105483172B (zh) * | 2016-01-06 | 2018-10-19 | 西南大学 | α-猪胰淀粉酶在催化串联反应合成硝基环丙烷类化合物中的应用及方法 |
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Effective date of registration: 20210112 Address after: 310000 rooms 1010, 1012 and 1016, block F, building 1, 1378 Wenyi West Road, Cangqian street, Yuhang District, Hangzhou City, Zhejiang Province Patentee after: Hangzhou xinbeisi biomedical Co.,Ltd. Address before: Hangzhou City, Zhejiang province 310036 Xiasha Higher Education Park forest Street No. 16 Patentee before: Hangzhou Normal University |
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Denomination of invention: A method for enzymatic synthesis of 2-substituted benzimidazole ring derivatives Granted publication date: 20151028 Pledgee: Guotou Taikang Trust Co.,Ltd. Pledgor: Hangzhou xinbeisi biomedical Co.,Ltd. Registration number: Y2024980011343 |
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