IL86004A - סינטזה של פפטיד-אמידים באמצעות שיטהשל פאסה מוצקת - Google Patents
סינטזה של פפטיד-אמידים באמצעות שיטהשל פאסה מוצקתInfo
- Publication number
- IL86004A IL86004A IL8600488A IL8600488A IL86004A IL 86004 A IL86004 A IL 86004A IL 8600488 A IL8600488 A IL 8600488A IL 8600488 A IL8600488 A IL 8600488A IL 86004 A IL86004 A IL 86004A
- Authority
- IL
- Israel
- Prior art keywords
- formula
- compound
- denotes
- hydrogen
- radicals
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 23
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 16
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 15
- 238000010532 solid phase synthesis reaction Methods 0.000 title claims abstract description 12
- 150000001408 amides Chemical class 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 27
- 239000001257 hydrogen Substances 0.000 claims abstract description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 125000006239 protecting group Chemical group 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 5
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims abstract 2
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 229920005989 resin Polymers 0.000 claims description 20
- 239000011347 resin Substances 0.000 claims description 20
- 238000005859 coupling reaction Methods 0.000 claims description 12
- 230000008878 coupling Effects 0.000 claims description 10
- 238000010168 coupling process Methods 0.000 claims description 10
- 150000001413 amino acids Chemical class 0.000 claims description 8
- 125000000539 amino acid group Chemical group 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 150000007513 acids Chemical class 0.000 claims description 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N Cysteine Chemical compound SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 4
- 241001071944 Cyta Species 0.000 claims description 3
- 150000008574 D-amino acids Chemical class 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 150000002923 oximes Chemical class 0.000 claims description 2
- 235000013350 formula milk Nutrition 0.000 claims 15
- 150000002431 hydrogen Chemical class 0.000 claims 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000006850 spacer group Chemical group 0.000 abstract description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 13
- 229940024606 amino acid Drugs 0.000 description 12
- -1 biphenylyl Chemical group 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 6
- 150000003862 amino acid derivatives Chemical class 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 150000008366 benzophenones Chemical class 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
- NPXUBWGJPZZFLL-UHFFFAOYSA-N 2-[4-(4-methoxybenzoyl)-2-methylphenoxy]acetic acid Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC=C(OCC(O)=O)C(C)=C1 NPXUBWGJPZZFLL-UHFFFAOYSA-N 0.000 description 2
- AMJFMXMQUNCOEX-UHFFFAOYSA-N 2-[4-(4-methoxybenzoyl)phenoxy]acetic acid Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC=C(OCC(O)=O)C=C1 AMJFMXMQUNCOEX-UHFFFAOYSA-N 0.000 description 2
- AENFXTBHJDGJHC-UHFFFAOYSA-N 2-[4-[(4-methoxyphenyl)methylamino]-2-methylphenoxy]acetic acid Chemical compound C1=CC(OC)=CC=C1CNC1=CC=C(OCC(O)=O)C(C)=C1 AENFXTBHJDGJHC-UHFFFAOYSA-N 0.000 description 2
- LVVWUBVPYVCLPV-UHFFFAOYSA-N 2-[4-[(4-methoxyphenyl)methylamino]phenoxy]acetic acid Chemical compound C1=CC(OC)=CC=C1CNC1=CC=C(OCC(O)=O)C=C1 LVVWUBVPYVCLPV-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 102400000050 Oxytocin Human genes 0.000 description 2
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 2
- 101800000989 Oxytocin Proteins 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 244000191761 Sida cordifolia Species 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 238000004873 anchoring Methods 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical class ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- LXKNFFSMAVWXOF-UHFFFAOYSA-N methyl 2-(2,6-dimethylphenoxy)acetate Chemical compound COC(=O)COC1=C(C)C=CC=C1C LXKNFFSMAVWXOF-UHFFFAOYSA-N 0.000 description 2
- MVTPAEZTSYWZHV-UHFFFAOYSA-N methyl 2-[4-(4-methoxybenzoyl)-2,6-dimethylphenoxy]acetate Chemical compound C1=C(C)C(OCC(=O)OC)=C(C)C=C1C(=O)C1=CC=C(OC)C=C1 MVTPAEZTSYWZHV-UHFFFAOYSA-N 0.000 description 2
- HJYXURCPMAHFAD-UHFFFAOYSA-N methyl 2-[4-(4-methoxybenzoyl)-2-methylphenoxy]acetate Chemical compound C1=C(C)C(OCC(=O)OC)=CC=C1C(=O)C1=CC=C(OC)C=C1 HJYXURCPMAHFAD-UHFFFAOYSA-N 0.000 description 2
- UOKZDUAWMYKLPB-UHFFFAOYSA-N methyl 2-[4-(4-methoxybenzoyl)phenoxy]acetate Chemical compound C1=CC(OCC(=O)OC)=CC=C1C(=O)C1=CC=C(OC)C=C1 UOKZDUAWMYKLPB-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 2
- 229960001723 oxytocin Drugs 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- VVQIIIAZJXTLRE-QMMMGPOBSA-N (2s)-2-amino-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound CC(C)(C)OC(=O)NCCCC[C@H](N)C(O)=O VVQIIIAZJXTLRE-QMMMGPOBSA-N 0.000 description 1
- MXWMFBYWXMXRPD-YFKPBYRVSA-N (2s)-2-azaniumyl-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoate Chemical compound CC(C)(C)OC(=O)C[C@H](N)C(O)=O MXWMFBYWXMXRPD-YFKPBYRVSA-N 0.000 description 1
- ONOURAAVVKGJNM-SCZZXKLOSA-N (2s,3r)-2-azaniumyl-3-phenylmethoxybutanoate Chemical compound [O-]C(=O)[C@@H]([NH3+])[C@@H](C)OCC1=CC=CC=C1 ONOURAAVVKGJNM-SCZZXKLOSA-N 0.000 description 1
- LGJXZWFPIDESNQ-UHFFFAOYSA-N (4-hydroxyphenyl)-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC=C(O)C=C1 LGJXZWFPIDESNQ-UHFFFAOYSA-N 0.000 description 1
- LXUNZSDDXMPKLP-UHFFFAOYSA-N 2-Methylbenzenethiol Chemical compound CC1=CC=CC=C1S LXUNZSDDXMPKLP-UHFFFAOYSA-N 0.000 description 1
- FDWNPTBEKDPXQC-UHFFFAOYSA-N 2-[4-[(4-methoxyanilino)methyl]-2,6-dimethylphenoxy]acetic acid Chemical compound CC1=CC(=CC(=C1OCC(=O)O)C)CNC2=CC=C(C=C2)OC FDWNPTBEKDPXQC-UHFFFAOYSA-N 0.000 description 1
- MOTKUPDKOHVDNL-UHFFFAOYSA-N 2-[4-[hydroxy-(4-methoxyphenyl)methyl]-2-methylphenoxy]acetic acid Chemical compound C1=CC(OC)=CC=C1C(O)C1=CC=C(OCC(O)=O)C(C)=C1 MOTKUPDKOHVDNL-UHFFFAOYSA-N 0.000 description 1
- CWUAIJUUDQWSMK-UHFFFAOYSA-N 2-[4-[hydroxy-(4-methoxyphenyl)methyl]phenoxy]acetic acid Chemical compound C1=CC(OC)=CC=C1C(O)C1=CC=C(OCC(O)=O)C=C1 CWUAIJUUDQWSMK-UHFFFAOYSA-N 0.000 description 1
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 description 1
- VGALFAWDSNRXJK-VIFPVBQESA-N L-aspartic acid beta-benzyl ester Chemical compound OC(=O)[C@@H](N)CC(=O)OCC1=CC=CC=C1 VGALFAWDSNRXJK-VIFPVBQESA-N 0.000 description 1
- QEFRNWWLZKMPFJ-YGVKFDHGSA-N L-methionine S-oxide Chemical compound CS(=O)CC[C@H](N)C(O)=O QEFRNWWLZKMPFJ-YGVKFDHGSA-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
- 229920006063 Lamide® Polymers 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- ILXDAXZQNSOSAE-UHFFFAOYSA-N [AlH3].[Cl] Chemical compound [AlH3].[Cl] ILXDAXZQNSOSAE-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 125000006307 alkoxy benzyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229940052294 amide local anesthetics Drugs 0.000 description 1
- 229920003180 amino resin Polymers 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 238000005915 ammonolysis reaction Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N benzyl alcohol Substances OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- OOYGSFOGFJDDHP-KMCOLRRFSA-N kanamycin A sulfate Chemical group OS(O)(=O)=O.O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N OOYGSFOGFJDDHP-KMCOLRRFSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- QLNWXBAGRTUKKI-UHFFFAOYSA-N metacetamol Chemical compound CC(=O)NC1=CC=CC(O)=C1 QLNWXBAGRTUKKI-UHFFFAOYSA-N 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- BZCKRPHEZOHHBK-UHFFFAOYSA-N methyl 2-phenoxyacetate Chemical compound COC(=O)COC1=CC=CC=C1 BZCKRPHEZOHHBK-UHFFFAOYSA-N 0.000 description 1
- IOPLHGOSNCJOOO-UHFFFAOYSA-N methyl 3,4-diaminobenzoate Chemical compound COC(=O)C1=CC=C(N)C(N)=C1 IOPLHGOSNCJOOO-UHFFFAOYSA-N 0.000 description 1
- SHDMMLFAFLZUEV-UHFFFAOYSA-N n-methyl-1,1-diphenylmethanamine Chemical compound C=1C=CC=CC=1C(NC)C1=CC=CC=C1 SHDMMLFAFLZUEV-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- ZERULLAPCVRMCO-UHFFFAOYSA-N sulfure de di n-propyle Natural products CCCSCCC ZERULLAPCVRMCO-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-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
- 229960004295 valine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
- C07K1/042—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers characterised by the nature of the carrier
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19873711866 DE3711866A1 (de) | 1987-04-08 | 1987-04-08 | Synthese von peptidamiden mittels festphasenmethode unter verwendung von saeurelabilen ankergruppen |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL86004A0 IL86004A0 (en) | 1988-09-30 |
| IL86004A true IL86004A (he) | 1994-06-24 |
Family
ID=6325145
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL8600488A IL86004A (he) | 1987-04-08 | 1988-04-07 | סינטזה של פפטיד-אמידים באמצעות שיטהשל פאסה מוצקת |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US4922015A (he) |
| EP (1) | EP0287882B1 (he) |
| JP (1) | JP2725780B2 (he) |
| KR (1) | KR970005473B1 (he) |
| AT (1) | ATE63108T1 (he) |
| AU (2) | AU605848B2 (he) |
| CA (1) | CA1337839C (he) |
| DE (2) | DE3711866A1 (he) |
| DK (1) | DK175624B1 (he) |
| ES (1) | ES2022508B3 (he) |
| GR (1) | GR3002283T3 (he) |
| IE (1) | IE60856B1 (he) |
| IL (1) | IL86004A (he) |
| PH (1) | PH27398A (he) |
| PT (1) | PT87185B (he) |
| ZA (1) | ZA882411B (he) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0322348B1 (de) * | 1987-12-22 | 1994-02-02 | Hoechst Aktiengesellschaft | Säurelabile Ankergruppen zur Synthese von Peptidamiden mittels Festphasenmethode |
| ES2097139T3 (es) * | 1989-12-04 | 1997-04-01 | Rhone Poulenc Chimie | Medio de reaccion y solubilizante de peptidos y procedimiento de sintesis de peptidos que utilizan este medio. |
| GB2251242B (en) * | 1990-12-31 | 1995-01-11 | Robert Ramage | Protecting compound |
| LT3872B (en) | 1993-12-06 | 1996-04-25 | Hoechst Ag | Novel peptides and pharmaceutical compositions containing them |
| DE4431317A1 (de) * | 1994-09-02 | 1996-03-07 | Biotechnolog Forschung Gmbh | Schutz- bzw. Ankergruppen und deren Verwendung |
| CN117486968B (zh) * | 2024-01-03 | 2024-03-29 | 深圳创元生物医药科技有限公司 | 一种类蛇毒肽的制备方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2683737A (en) * | 1951-12-17 | 1954-07-13 | Searle & Co | Aromatic hydrocarbon esters of basically substituted aralkylcarbamates and salts thereof |
| CA945164A (en) * | 1970-09-04 | 1974-04-09 | Imperial Chemical Industries Limited | Leucauramine derivatives |
| GB1539897A (en) * | 1975-02-12 | 1979-02-07 | Orchimed Sa | Phenoxypropionic acid derivatives |
| US4101721A (en) * | 1976-12-09 | 1978-07-18 | Wisconsin Alumni Research Foundation | Solid phase synthesis of protected peptides |
| FR2428629A1 (fr) * | 1978-06-14 | 1980-01-11 | Hexachimie | Nouveaux composes bis(aryloxycarboxyliques), leur preparation et leur utilisation en therapeutique |
| JPS5531039A (en) * | 1978-08-25 | 1980-03-05 | Sumitomo Chem Co Ltd | Oximecarbamate derivative, its preparation, and microbicide and herbicide containing the same |
| DE2926049A1 (de) * | 1979-06-28 | 1981-01-08 | Basf Ag | M-anilidurethane und diese enthaltende herbizide |
| SI8310221A8 (en) * | 1982-02-04 | 1995-10-31 | Wellcome Found | Process for obtaining new pyridil compounds |
| GB2169901A (en) * | 1984-12-11 | 1986-07-23 | Lkb Biochrom Ltd | method for a solid phase synthesis of a linear combination of amino acid residues. |
| DE3628650A1 (de) * | 1986-03-12 | 1987-09-24 | Bayer Ag | Renininhibitoren, verfahren zur herstellung und ihre verwendung |
-
1987
- 1987-04-08 DE DE19873711866 patent/DE3711866A1/de not_active Withdrawn
-
1988
- 1988-04-02 AT AT88105352T patent/ATE63108T1/de not_active IP Right Cessation
- 1988-04-02 ES ES88105352T patent/ES2022508B3/es not_active Expired - Lifetime
- 1988-04-02 EP EP88105352A patent/EP0287882B1/de not_active Expired - Lifetime
- 1988-04-02 DE DE8888105352T patent/DE3862605D1/de not_active Expired - Lifetime
- 1988-04-06 US US07/178,232 patent/US4922015A/en not_active Expired - Lifetime
- 1988-04-07 AU AU14371/88A patent/AU605848B2/en not_active Expired
- 1988-04-07 CA CA000563530A patent/CA1337839C/en not_active Expired - Lifetime
- 1988-04-07 PT PT87185A patent/PT87185B/pt not_active IP Right Cessation
- 1988-04-07 DK DK198801893A patent/DK175624B1/da not_active IP Right Cessation
- 1988-04-07 IE IE103588A patent/IE60856B1/en not_active IP Right Cessation
- 1988-04-07 IL IL8600488A patent/IL86004A/he not_active IP Right Cessation
- 1988-04-07 JP JP63084232A patent/JP2725780B2/ja not_active Expired - Lifetime
- 1988-04-07 KR KR1019880003870A patent/KR970005473B1/ko not_active Expired - Lifetime
- 1988-04-07 ZA ZA882411A patent/ZA882411B/xx unknown
- 1988-06-06 PH PH36753A patent/PH27398A/en unknown
-
1990
- 1990-10-01 AU AU63686/90A patent/AU629049B2/en not_active Expired
-
1991
- 1991-07-10 GR GR91400603T patent/GR3002283T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK189388D0 (da) | 1988-04-07 |
| AU6368690A (en) | 1991-02-21 |
| PT87185A (pt) | 1988-05-01 |
| ZA882411B (en) | 1988-09-28 |
| PT87185B (pt) | 1992-07-31 |
| IE60856B1 (en) | 1994-08-24 |
| KR880012638A (ko) | 1988-11-28 |
| JP2725780B2 (ja) | 1998-03-11 |
| DK189388A (da) | 1988-10-09 |
| DK175624B1 (da) | 2004-12-27 |
| ES2022508B3 (es) | 1991-12-01 |
| CA1337839C (en) | 1995-12-26 |
| EP0287882B1 (de) | 1991-05-02 |
| GR3002283T3 (en) | 1992-12-30 |
| AU629049B2 (en) | 1992-09-24 |
| AU605848B2 (en) | 1991-01-24 |
| JPS63267748A (ja) | 1988-11-04 |
| ATE63108T1 (de) | 1991-05-15 |
| PH27398A (en) | 1993-06-21 |
| EP0287882A1 (de) | 1988-10-26 |
| DE3711866A1 (de) | 1988-10-27 |
| KR970005473B1 (ko) | 1997-04-16 |
| DE3862605D1 (de) | 1991-06-06 |
| IE881035L (en) | 1988-10-08 |
| AU1437188A (en) | 1988-10-13 |
| US4922015A (en) | 1990-05-01 |
| IL86004A0 (en) | 1988-09-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| KB | Patent renewed | ||
| HP | Change in proprietorship | ||
| KB | Patent renewed | ||
| EXP | Patent expired |