CN103864885B - The application of 1-hydroxyl-1,2,3-phentriazine-4 (3H)-one in Peptide systhesis - Google Patents
The application of 1-hydroxyl-1,2,3-phentriazine-4 (3H)-one in Peptide systhesis Download PDFInfo
- Publication number
- CN103864885B CN103864885B CN201410107410.6A CN201410107410A CN103864885B CN 103864885 B CN103864885 B CN 103864885B CN 201410107410 A CN201410107410 A CN 201410107410A CN 103864885 B CN103864885 B CN 103864885B
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- phentriazine
- hydroxyl
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- amino acid
- polypeptide
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 59
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 50
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 32
- 229920001184 polypeptide Polymers 0.000 claims abstract description 29
- 150000001413 amino acids Chemical class 0.000 claims abstract description 26
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims abstract description 15
- -1 carbobenzoxy-(Cbz) Chemical class 0.000 claims abstract description 14
- 150000004702 methyl esters Chemical class 0.000 claims abstract description 9
- 150000007524 organic acids Chemical class 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 120
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 58
- 238000006243 chemical reaction Methods 0.000 claims description 56
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 49
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 48
- 239000000243 solution Substances 0.000 claims description 39
- 239000011734 sodium Substances 0.000 claims description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 238000004821 distillation Methods 0.000 claims description 18
- 239000005457 ice water Substances 0.000 claims description 18
- 239000012074 organic phase Substances 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 18
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 18
- 239000013078 crystal Substances 0.000 claims description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- 235000002639 sodium chloride Nutrition 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 238000006482 condensation reaction Methods 0.000 claims description 10
- 238000000926 separation method Methods 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 9
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 claims description 9
- 238000004440 column chromatography Methods 0.000 claims description 9
- 229960004132 diethyl ether Drugs 0.000 claims description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 9
- 239000012046 mixed solvent Substances 0.000 claims description 9
- 238000001953 recrystallisation Methods 0.000 claims description 9
- 238000005406 washing Methods 0.000 claims description 9
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000010792 warming Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 12
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000006872 improvement Effects 0.000 abstract description 3
- 230000002262 irrigation Effects 0.000 abstract 1
- 238000003973 irrigation Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 14
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 9
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- RRONHWAVOYADJL-HNNXBMFYSA-N (2s)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 RRONHWAVOYADJL-HNNXBMFYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 230000006340 racemization Effects 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 102000014413 Neuregulin Human genes 0.000 description 1
- 108050003475 Neuregulin Proteins 0.000 description 1
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241000282894 Sus scrofa domesticus Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- CUCAZZQPISJXOS-QWRGUYRKSA-N methyl (2s)-2-[[(2s)-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoate Chemical compound COC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 CUCAZZQPISJXOS-QWRGUYRKSA-N 0.000 description 1
- CWVOQXJRSJVARM-HOTGVXAUSA-N methyl (2s)-3-methyl-2-[[(2s)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]butanoate Chemical compound COC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)OCC1=CC=CC=C1 CWVOQXJRSJVARM-HOTGVXAUSA-N 0.000 description 1
- SIHNOQQFBTTYLO-YJBOKZPZSA-N methyl (2s)-3-phenyl-2-[[(2s)-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H](C)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 SIHNOQQFBTTYLO-YJBOKZPZSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
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Priority Applications (1)
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CN201410107410.6A CN103864885B (en) | 2014-03-21 | 2014-03-21 | The application of 1-hydroxyl-1,2,3-phentriazine-4 (3H)-one in Peptide systhesis |
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CN201410107410.6A CN103864885B (en) | 2014-03-21 | 2014-03-21 | The application of 1-hydroxyl-1,2,3-phentriazine-4 (3H)-one in Peptide systhesis |
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CN103864885A CN103864885A (en) | 2014-06-18 |
CN103864885B true CN103864885B (en) | 2016-01-13 |
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Families Citing this family (5)
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CN109438550A (en) * | 2018-09-21 | 2019-03-08 | 重庆奥舍生物化工有限公司 | Application of the novel carbonium ion polypeptide condensing agent in Peptide systhesis |
CN109336832A (en) * | 2018-09-21 | 2019-02-15 | 重庆奥舍生物化工有限公司 | A kind of polypeptide condensing agent and preparation method thereof for polypeptide drug synthesis |
CN109232647A (en) * | 2018-09-21 | 2019-01-18 | 重庆奥舍生物化工有限公司 | Polypeptide condensing agent 1- (diethoxy phosphoryl oxy) -1,2,3- phentriazine -4- ketone and preparation method thereof |
CN109336948A (en) * | 2018-09-21 | 2019-02-15 | 重庆奥舍生物化工有限公司 | Application of the novel organophosphorus polypeptide condensing agent in Peptide systhesis |
CN109232648A (en) * | 2018-10-08 | 2019-01-18 | 重庆科脉生物化工有限公司 | A kind of polypeptide condensing agent containing phosphamide and preparation method thereof for polypeptide drugs synthesis |
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JPS5821627B2 (en) * | 1974-05-07 | 1983-05-02 | 藤沢薬品工業株式会社 | Sulfone sulfone ester |
US6013764A (en) * | 1996-07-17 | 2000-01-11 | Ortho Pharmaceutical Corp. | Liquid phase peptide synthesis of KL-4 pulmonary surfactant |
CN1978436A (en) * | 2005-11-30 | 2007-06-13 | 中国科学院兰州化学物理研究所 | Polypeptide synthetic condensation agent 3-hydroxy-4-oxy-3,4-dihydro-1,2,3-benzotriazozine synthesizing method |
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Effective date of registration: 20180314 Address after: 230000 Anhui province Hefei high tech Zone Xiang Chang Road No. 168 science and Technology Industrial Park C6 4 layer Patentee after: HEFEI BANKPEPTIDE BIOLOGICAL TECHNOLOGY CO.,LTD. Address before: 453007 Xinxiang East Road, Makino District, Henan, No. 46 Patentee before: Henan Normal University |
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Effective date of registration: 20231212 Address after: Unit B04, building 17, No. 122, Yong'an Road, Hushuguan Town, high tech Zone, Suzhou, Jiangsu 215151 Patentee after: Suzhou modiff Biotechnology Co.,Ltd. Address before: 230000, 4th Floor, C6 #, Science and Technology Industrial Park, No. 168 Xiangzhang Avenue, High tech Zone, Hefei City, Anhui Province Patentee before: HEFEI BANKPEPTIDE BIOLOGICAL TECHNOLOGY CO.,LTD. |
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