CN112625220A - Method for preparing protecting group-free same (different) type sugar-containing polymer by ROMP polymerization reaction - Google Patents
Method for preparing protecting group-free same (different) type sugar-containing polymer by ROMP polymerization reaction Download PDFInfo
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- CN112625220A CN112625220A CN202011425517.7A CN202011425517A CN112625220A CN 112625220 A CN112625220 A CN 112625220A CN 202011425517 A CN202011425517 A CN 202011425517A CN 112625220 A CN112625220 A CN 112625220A
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- compound
- protecting group
- sugar
- containing polymer
- reaction
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- 235000000346 sugar Nutrition 0.000 title claims abstract description 60
- 229920000642 polymer Polymers 0.000 title claims abstract description 40
- 238000000034 method Methods 0.000 title claims abstract description 28
- 238000007152 ring opening metathesis polymerisation reaction Methods 0.000 title claims abstract description 26
- 238000006116 polymerization reaction Methods 0.000 title claims abstract description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 82
- 239000000178 monomer Substances 0.000 claims abstract description 45
- 238000006243 chemical reaction Methods 0.000 claims abstract description 41
- 125000006239 protecting group Chemical group 0.000 claims abstract description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 19
- 150000001720 carbohydrates Chemical class 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 9
- -1 alkyne compound Chemical group 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 49
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 18
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 18
- 229940045803 cuprous chloride Drugs 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 11
- 229940125898 compound 5 Drugs 0.000 claims description 11
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 10
- 229940125904 compound 1 Drugs 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 claims description 8
- 229940125782 compound 2 Drugs 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims description 7
- 229940126214 compound 3 Drugs 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- LVMGIHIXFUCCIK-PHYPRBDBSA-N (2S,3R,4S,5R,6R)-2-azido-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound N(=[N+]=[N-])[C@]1(O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO LVMGIHIXFUCCIK-PHYPRBDBSA-N 0.000 claims description 5
- WQZGKKKJIJFFOK-PQMKYFCFSA-N alpha-D-mannose Chemical group OC[C@H]1O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-PQMKYFCFSA-N 0.000 claims description 5
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 5
- 238000004440 column chromatography Methods 0.000 claims description 5
- LVMGIHIXFUCCIK-DVKNGEFBSA-N diazonio-[(2s,3r,4s,5s,6r)-2,3,4,5-tetrahydroxy-6-(hydroxymethyl)oxan-2-yl]azanide Chemical compound OC[C@H]1O[C@](O)([N-][N+]#N)[C@H](O)[C@@H](O)[C@@H]1O LVMGIHIXFUCCIK-DVKNGEFBSA-N 0.000 claims description 5
- 239000011347 resin Substances 0.000 claims description 5
- 229920005989 resin Polymers 0.000 claims description 5
- LVMGIHIXFUCCIK-RWOPYEJCSA-N diazonio-[(2r,3s,4s,5s,6r)-2,3,4,5-tetrahydroxy-6-(hydroxymethyl)oxan-2-yl]azanide Chemical compound OC[C@H]1O[C@@](O)([N-][N+]#N)[C@@H](O)[C@@H](O)[C@@H]1O LVMGIHIXFUCCIK-RWOPYEJCSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- AREPHAPHABGCQP-UHFFFAOYSA-N 1-(dimethylamino)-3-[2-[2-(4-methoxyphenyl)ethyl]phenoxy]propan-2-ol Chemical compound C1=CC(OC)=CC=C1CCC1=CC=CC=C1OCC(O)CN(C)C AREPHAPHABGCQP-UHFFFAOYSA-N 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 claims 1
- 239000011988 third-generation catalyst Substances 0.000 abstract description 6
- 238000011160 research Methods 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 230000001681 protective effect Effects 0.000 abstract 2
- 238000006845 Michael addition reaction Methods 0.000 abstract 1
- 125000003518 norbornenyl group Chemical class C12(C=CC(CC1)C2)* 0.000 abstract 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 26
- HEDRZPFGACZZDS-MICDWDOJSA-N deuterated chloroform Substances [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 229920001282 polysaccharide Polymers 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 238000005227 gel permeation chromatography Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- WZEWDEAIHCUMKY-UHFFFAOYSA-N 2,2,5-trimethyl-1,3-dioxane-5-carboxylic acid Chemical compound CC1(C)OCC(C)(C(O)=O)CO1 WZEWDEAIHCUMKY-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 238000010526 radical polymerization reaction Methods 0.000 description 4
- 241001436679 Adama Species 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 108010005774 beta-Galactosidase Proteins 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000011984 grubbs catalyst Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241001575999 Hakka Species 0.000 description 2
- 235000016278 Mentha canadensis Nutrition 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 125000002355 alkine group Chemical group 0.000 description 2
- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 2
- 238000012661 block copolymerization Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229920000550 glycopolymer Polymers 0.000 description 2
- 125000003147 glycosyl group Chemical group 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000012712 reversible addition−fragmentation chain-transfer polymerization Methods 0.000 description 2
- 235000010378 sodium ascorbate Nutrition 0.000 description 2
- 229960005055 sodium ascorbate Drugs 0.000 description 2
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 2
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- KSRDTSABQYNYMP-VFUOTHLCSA-N (2r,3r,4s,5s,6r)-2-azido-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OC[C@H]1O[C@@H](N=[N+]=[N-])[C@H](O)[C@@H](O)[C@@H]1O KSRDTSABQYNYMP-VFUOTHLCSA-N 0.000 description 1
- KSRDTSABQYNYMP-PQMKYFCFSA-N (2s,3s,4s,5s,6r)-2-azido-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OC[C@H]1O[C@H](N=[N+]=[N-])[C@@H](O)[C@@H](O)[C@@H]1O KSRDTSABQYNYMP-PQMKYFCFSA-N 0.000 description 1
- WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 1
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 1
- 101710141544 Allatotropin-related peptide Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-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
- 238000006959 Williamson synthesis reaction Methods 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010560 atom transfer radical polymerization reaction Methods 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G61/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
- C08G61/12—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule
- C08G61/122—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule derived from five- or six-membered heterocyclic compounds, other than imides
- C08G61/123—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule derived from five- or six-membered heterocyclic compounds, other than imides derived from five-membered heterocyclic compounds
- C08G61/125—Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule derived from five- or six-membered heterocyclic compounds, other than imides derived from five-membered heterocyclic compounds with a five-membered ring containing one oxygen atom in the ring
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
- C08G2261/10—Definition of the polymer structure
- C08G2261/12—Copolymers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
- C08G2261/10—Definition of the polymer structure
- C08G2261/14—Side-groups
- C08G2261/142—Side-chains containing oxygen
- C08G2261/1426—Side-chains containing oxygen containing carboxy groups (COOH) and/or -C(=O)O-moieties
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
- C08G2261/10—Definition of the polymer structure
- C08G2261/14—Side-groups
- C08G2261/143—Side-chains containing nitrogen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
- C08G2261/30—Monomer units or repeat units incorporating structural elements in the main chain
- C08G2261/32—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain
- C08G2261/324—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain condensed
- C08G2261/3241—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain condensed containing one or more nitrogen atoms as the only heteroatom, e.g. carbazole
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
- C08G2261/30—Monomer units or repeat units incorporating structural elements in the main chain
- C08G2261/32—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain
- C08G2261/324—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain condensed
- C08G2261/3242—Monomer units or repeat units incorporating structural elements in the main chain incorporating heteroaromatic structural elements in the main chain condensed containing one or more oxygen atoms as the only heteroatom, e.g. benzofuran
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
- C08G2261/40—Polymerisation processes
- C08G2261/41—Organometallic coupling reactions
- C08G2261/418—Ring opening metathesis polymerisation [ROMP]
Abstract
The invention relates to a method for preparing a protective group-free homo (iso) saccharide-containing polymer by ROMP polymerization, which comprises the steps of firstly combining Michael addition reaction to prepare a double-terminal alkyne compound in a proper solvent, and then using copper-catalyzed click chemistry reaction in methanol at room temperature to obtain a norbornene derivative of a protective group-free iso-saccharide monomer. Then under the action of Grubbs third-generation catalyst, ring-opening metathesis polymerization is carried out, and the sugar-containing polymer of the same (different) type without protective group with controllable molecular weight and narrow molecular weight distribution is successfully prepared in N, N-dimethylformamide solvent at 50 ℃. The invention provides a feasible way for artificially synthesizing the same (different) type sugar-containing polymer without the protecting group with ordered side chain structure, and has important significance for the research of the sugar-containing polymer without the protecting group.
Description
Technical Field
The invention belongs to the technical field of synthesis of protecting group-free homo (hetero) sugar-containing polymers, and relates to a method for preparing protecting group-free homo (hetero) sugar-containing polymers by ROMP polymerization reaction.
Background
Sugar-containing polymers (glycopolymers) are a class of synthetic macromolecules that will contain sugar groups and have good water solubility, biological stain resistance, molecular recognition, and good "sugar clustering". Since a series of sugar-containing polyacrylamides were synthesized by a radical polymerization method in 1978 for the first time, with the rapid development of polymer synthesis chemistry, particularly the synthesis technology of functional sugar polymers, several strategies for controlled radical polymerization (e.g., reversible addition-fragmentation chain transfer polymerization (RAFT), nitroxide-controlled radical polymerization (NMP), copper-catalyzed living radical polymerization (TMM-LRP, ATRP, and SET-LRP) have been continuously developed, utilized, and improved to prepare sugar-containing polymers with better properties and controllable components and structures. The research of artificially synthesizing the sugar-containing polymer is very important for the application of the sugar material and the theoretical research.
At present, the research on the synthesis method of sugar-containing polymers is mainly based on the two aspects of the polymerization of glycosylated monomers and the post-polymerization modification of polymer main chains and sugar-containing derivatives. The polymerization of the glycosylation monomer refers to that the polymer obtains the glycosyl function and the characteristics of other functional groups by utilizing the homopolymerization of the sugar-containing monomer or the copolymerization of the sugar-containing monomer and other functional monomers, thereby meeting the requirements of specific applications and obtaining the deprotected sugar-containing polymer without a complicated purification process. Meanwhile, Ring Opening Metathesis Polymerization (ROMP) can prepare polymers with narrow molecular weight distribution and uniform molecular structure. However, the synthesis route of the sugar monomer without the protecting group is complex, the required monomer has high purity and is expensive, the sugar monomer without the protecting group has certain insolubility in an organic solvent, and the reaction condition requires harsh polymerization conditions, so that further research and development are needed for the ROMP reaction of the sugar monomer without the protecting group in a homogeneous solvent.
Disclosure of Invention
The invention aims to provide a method for preparing a protecting group-free homo (hetero) saccharide-containing polymer by ROMP polymerization reaction so as to artificially synthesize a protecting group-free homo (hetero) saccharide-containing polymer with ordered side chain structures.
The purpose of the invention can be realized by the following technical scheme:
a method for preparing a protecting group-free same (different) type sugar-containing polymer by ROMP polymerization reaction comprises the step of carrying out ROMP polymerization reaction on a protecting group-free same (different) type sugar monomer and a Grubbs third-generation catalyst in an N, N-Dimethylformamide (DMF) solvent under an inert gas atmosphere to obtain a target product.
Further, the temperature of ROMP polymerization reaction is 40-60 ℃, and the reaction time is 12-18 h.
Furthermore, the molar ratio of the same (different) sugar monomer without the protecting group to the Grubbs third-generation catalyst is 10-15: 1.
Further, after the monomers are completely polymerized, adding vinyl ethyl ether to terminate the polymerization reaction, and performing post-treatment on the obtained reaction product to obtain a target product, wherein the post-treatment process specifically comprises the following steps: adding methanol into the reaction solution, stirring and settling, washing and drying the precipitated solid, and obtaining the target product.
Further, the non-protecting group iso (iso) sugar monomer is alpha-D-mannose-containing monomer (i.e. M)1Man + Man), beta-D-glucose monomer (i.e., M)2Man + β Glu) or β -D-galactose monomer (i.e., M)3Man + β Gal), i.e. the chemical structural formulae respectively as follows:
further, the protecting group-free iso (iso) saccharide monomer is prepared by the following method:
(1) reacting furan and maleic anhydride in a solvent at room temperature to generate a compound 1;
(2) reacting the compound 1 with ethanolamine in methanol to generate a compound 2;
(3) reacting the compound 2, TDC, N' -dicyclohexylcarbodiimide and 4-dimethylaminopyridine in dichloromethane to generate a compound 3;
(4) compound 3 and Dowex-H+Reacting the resin at normal temperature to generate a compound 4;
(5) reacting the compound 4, 4-pentanoic anhydride and 4-dimethylamino pyridine in dichloromethane to generate a compound 5;
(6) the compound 5 and 1-azido-alpha-D-mannopyranose react in methanol under the catalysis of cuprous chloride at normal temperature to generate a compound M1And compound M' (i.e., Man + Alkyne);
(7) dissolving the compound M' and 1-azido-beta-D-glucopyranose in methanol, adding cuprous chloride as a catalyst, stirring at normal temperature, filtering to remove insoluble substances, washing with methanol, and performing column chromatography to obtain the compound M2;
(8) Dissolving the compound M' and 1-azido-beta-D-galactopyranose in methanol, adding cuprous chloride as catalyst, stirring at normal temperature, filtering to remove insoluble substances, washing with methanol, and performing column chromatography to obtain compound M3;
The resulting Compound M1Compound M2And a compound M3Namely alpha-D-mannose monomer, beta-D-glucose monomer or beta-D-galactose monomer;
the chemical structure of compound M' is as follows:
furthermore, in the step (1), the molar ratio of the maleic anhydride to the furan is (0.2-0.4): 1, the reaction process is specifically as follows: the reaction was carried out at room temperature for 24 h.
Further, in the step (2), the molar ratio of the compound 1 to the ethanolamine is (200-): 1, the reaction process is specifically as follows: the mixture was stirred at 0 ℃ for 1 hour and then reacted at room temperature for 1 hour.
Furthermore, in the step (3), the mass ratio of the compound 2, TDC, N' -dicyclohexylcarbodiimide and 4-dimethylaminopyridine is (9-12): (8-12): (14-18): 1.6;
the reaction process specifically comprises the following steps: stirred at room temperature for 24 h.
Further, in step (5), the molar ratio of compound 4, 4-pentanoic anhydride and 4-dimethylaminopyridine is 1: (2-4): (0.4-0.6);
the reaction process specifically comprises the following steps: the reaction was stirred at room temperature for 16 h.
Further, in the step (6), the molar ratio of the compound 5, 1-azido-alpha-D-mannopyranose to cuprous chloride is 1: (0.8-1.2): (1.5-2.5);
in the step (7), the molar ratio of the compound M', 1-azido-beta-D-glucopyranose to cuprous chloride is 1: (1.0-1.4): (2.5-3.5);
in the step (8), the molar ratio of the compound M', the 1-azido-beta-D-galactopyranose and the cuprous chloride is 1: (1.0-1.4): (2.5-3.5).
The invention selects three monosaccharides prepared by early stage experiments: alpha-D-mannose monomer, beta-D-glucose monomer and beta-D-galactose monomer. Importantly, in the preparation of the sugar-containing monomer, a stronger acylating agent 4-valeric anhydride is selected, and the acylating agent is suitable for phenolic hydroxyl which is difficult to react by a direct esterification method or hydroxyl compounds with larger steric hindrance. Secondly, in order to seek a reaction capable of generating a complex compound, cuprous chloride is selected as a catalyst to react in a methanol solution at normal temperature, so that the problems that sugar without a protecting group is difficult to dissolve in an organic solvent, and the hydrolysis of ester is inhibited by adding alcohol into a reaction system are solved, and the sugar monomer without the protecting group and the (different) type is obtained by reacting at room temperature. Then, ring-opening metathesis polymerization is carried out, and the same (different) type sugar-containing polymer which has regular structure, controllable molecular weight and narrow molecular weight distribution and contains no protecting group is prepared in N, N-dimethylformamide solvent under the environment of 50 ℃ under the action of Grubbs third-generation catalyst.
The method is simple, efficient and convenient to operate, different glycosyl units are introduced into the same monomer, and the side chain structure is controllable. The invention solves the disadvantages of introducing heterogeneous sugar units by post-modification and block copolymerization methods, improves the difficulty of homogeneous polymerization of sugar-containing monomers without protective groups, and widens the synthetic route of sugar-containing polymers.
Compared with the prior art, the invention has the following advantages:
(1) the invention selects 4-valeric anhydride as an acylating agent for the first time and selects cuprous chloride as a catalyst, thereby effectively improving the problem of ester hydrolysis, successfully preparing three protecting group-free same (different) type sugar-containing monomers, and having stable and high-efficiency synthesis method.
(2) The invention uses Grubbs three-generation catalyst at 50 ℃ for the first time to prepare the sugar-containing polymer containing the same (different) type sugar monomer without the protecting group, which has regular structure, controllable molecular weight and narrow molecular weight distribution through ring-opening metathesis polymerization. The invention solves the disadvantages of introducing heterogeneous sugar units by post-modification and block copolymerization methods, and widens the synthetic route of the sugar-containing polymer.
(3) The heterogeneous carbohydrate-containing polymer synthesized by the invention has controllable side chain structure and regular structure, can be applied to the research of biological protein specificity identification, and can also be used for preparing biological diagnostic materials with special functions.
Drawings
FIG. 1 shows the reaction of alpha-D-mannosylazide in CDCl3In (500MHz)1H NMR。
FIG. 2 shows beta-D-glucopyranosyl azide in CDCl3In (500MHz)1H NMR。
FIG. 3 shows beta-D-galactosylalkylazide in CDCl3In (500MHz)1H NMR。
FIG. 4 shows the reaction of Compound 5 in CDCl3In (500MHz)1H NMR。
FIG. 5 shows the reaction of Compound 5 in CDCl3In (125MHz)13C NMR。
FIG. 6 shows Compound M1At D2In O (500MHz)1H NMR。
FIG. 7 shows Compound M1At D2In O (125MHz)13C NMR。
FIG. 8 shows the compound M' at D2In O (500MHz)1H NMR。
FIG. 9 shows the compound M' at D2In O (125MHz)13C NMR。
FIG. 10 shows Compound M2At D2In O (500MHz)1H NMR。
FIG. 11 shows Compound M2At D2In O (125MHz)13C NMR。
FIG. 12 shows Compound M3At D2In O (500MHz)1H NMR。
FIG. 13 shows Compound M3At D2In O (125MHz)13C NMR。
FIG. 14 shows sugar Polymer P (Man + Man) at D2In O (500MHz)1H NMR。
FIG. 15 shows sugar Polymer P (Man + β Glu) at D2In O (500MHz)1H NMR。
FIG. 16 shows the saccharide polymers P (Man +. beta. Gal) at D2In O (500MHz)1H NMR。
FIG. 17 is a gel chromatography chart of the protecting group-free homo (hetero) saccharide-containing polymer.
FIG. 18 is a schematic of the synthesis scheme of the present invention.
Detailed Description
The invention is described in detail below with reference to the figures and specific embodiments. The present embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation manner and a specific operation process are given, but the scope of the present invention is not limited to the following embodiments.
The invention is described in detail below with reference to the synthetic process scheme of FIG. 18.
In each of the following examples, three azido sugars (. alpha.Man-OAc-N)3、βGal-OAc-N3、βGlu-OAc-N3) Synthesized according to the methods of the following two documents; maleic anhydride, a product of Hakka Adama reagents, Inc.; 4-pentanoic anhydride, a product of Hakka Adama reagent, Inc.; 4-dimethylaminopyridine, available from Haemax Agents, Inc. of Shanghai; (ii) a Dowex-H+Resins, products of shanghai hadamard reagents ltd; grubbs' third generation catalyst, product of Haicha Adama reagents, Inc.; 2,2, 5-trimethyl-1, 3-dioxane-5-carboxylic acid, a product of Shanghai Adama reagent, Inc.; all other raw materials are commercially available analytical reagents, wherein anhydrous methanol, anhydrous Dichloromethane (DCM) and anhydrous N, N-Dimethylformamide (DMF) (containing molecular sieve, water content is less than or equal to 0.05%) are all purchased from Shanghai Michelin Biochemical Co., Ltd. Among them, reference 1 is a. bianchi and a. bernardi, j.org.chem.,2006,71, 4565-; document 2 is V.Percec, P.Leowanawat, H.J.Sun, O.Kulikov, C.D.Nusbaum, T.M.Tran, A.Bertin, D.A.Wilson, M.Peterca, S.Zhang, N.P.Kamat, K.Vargo, D.Moock, E.D.Johnston, D.A.Hammer, D.J.Pochan, Y.Chen, Y.M.Charre, T.C.Shiao, M.Bergeron-Brlek, S.Andre, R.Roy, H.J.Gabius and P.A.Heiney, J.Am.Chem.Soc.,2013,135, 55.9077.9077.
Example 1
Synthesis of Compound 1
Maleic anhydride (50g, 0.51mol) was charged to a dry round bottom flask and 250mL of diethyl ether was added. After the maleic anhydride had dissolved, furan (125mL, 1.72mol) was added. After the reaction was completed for 24 hours at room temperature, ether and furan were removed by filtration, and washed three times with ether to obtain 76g of a white solid (i.e., compound 1) in 90% yield.
1H NMR(500MHz,CDCl3,ppm)δ=6.54(s,2H),5.30(s,2H),3.80(m,2H),3.70(m,2H),2.91(s,2H),2.32(s,1H).
Example 2
Synthesis of Compound 2
Compound 1(10.8g, 51.6mmol) and methanol (210mL) were stirred at 0 ℃. Then ethanolamine (11mL,0.18mmol) is dissolved in 30mL of methanol and is dripped into the reaction system for no less than 30min, then the stirring is continued for 1h at the temperature of 0 ℃, the ice bath is removed, the reaction is carried out for 1h at the room temperature, and the heating is carried out for reflux for 12h at the temperature of 65 ℃. After the reaction was completed, the reaction mixture was cooled to room temperature, and then recrystallized after removing a large amount of methanol by distillation under reduced pressure, and the filtrate was washed with petroleum ether to obtain 16g of a white solid (i.e., compound 2) in a yield of 64%.
1H NMR(500MHz,CDCl3)δ=6.52(s,2H),5.28(s,2H),3.76(s,2H),3.70(s,2H),2.89(s,2H),2.15(s,1H).
Example 3
Synthesis of Compound 3
TDC (2,2, 5-trimethyl-1, 3-dioxane-5-carboxylic acid) (9.0g, 51.6mmol) and compound 2(10.8g, 51.6mmol) were dissolved in 120mL of anhydrous dichloromethane. N, N' -Dicyclohexylcarbodiimide (DCC) (16g, 77.5mmol) and 4-Dimethylaminopyridine (DMAP) (1.6g, 13.1mmol) were then added and stirred at room temperature for 24 h. After filtration to remove insoluble impurities, the filtrate was concentrated and purified by petroleum ether/ethyl acetate 1: 1 as eluent, the viscous oil obtained after purification by column chromatography on silica gel, the product being dried in vacuo. 15.65g of a white solid (i.e., Compound 3) was obtained in 83% yield.
1H NMR(500MHz,CDCl3,ppm)δ=6.51(s,2H),5.26(s,2H),4.29(t,J=5.2Hz,2H),4.13(d,J=11.8Hz,2H),3.78(t,J=5.2Hz,2H),3.59(d,J=11.8Hz,2H),2.86(s,2H),1.39(d,J=17.7Hz,6H),1.18(s,3H).
Example 4
Synthesis of Compound 4
Dissolving compound 3(42.5g, 116mmol) in methanol, stirring at 35 deg.C for reaction, tracking reaction by TLC, adding appropriate amount of Dowex-H after reaction+The reaction solution was neutralized with a resin, the insoluble resin was removed by filtration, the filtrate was concentrated, and purification and separation were performed using a silica gel column (ethyl acetate 100%) to obtain 35.6g of a white solid (i.e., compound 4) in 94% yield.
1H NMR(500MHz,CDCl3,ppm)δ=6.53(s,2H),5.28(s,2H),4.33(s,2H),3.83–3.76(m,4H),3.68(d,J=11.4Hz,2H),2.91(s,2H),2.76(s,2H),1.04(s,3H).
Example 5
Synthesis of Compound 5
Compound 4(3.25g, 10mmol) was added to dry dichloromethane (40mL) with stirring, nitrogen purged, followed by 4-pentanoic anhydride (5.34g, 30mmol), 4-dimethylaminopyridine (0.66g, 5.4mmol), and pyridine (7.6 mL). Stirring at room temperature for 16h, monitoring the reaction by TLC, and using NaHSO to react the reaction solution4The aqueous solution and saturated aqueous sodium bicarbonate solution were each washed three times, and the organic phase was dried over anhydrous sodium sulfate and directly passed through a silica gel column to give 4.4g of pale yellow 5 (i.e., compound 5) in 90% yield1H NMR and13c NMR is shown in FIGS. 4 and 5.
1H NMR(500MHz,CDCl3)δ=6.50(s,2H),5.28(s,2H),4.22(d,J=12.5Hz,4H),4.17(s,2H),3.74(t,J=5.0Hz,2H),2.87(s,2H),2.53(t,J=7.0Hz,4H),2.49~2.41(m,4H),1.96(s,2H),1.21(s,3H).13C NMR(125MHz,CDCl3)δ=176.03,172.31,171.21,136.57,82.35,80.87,69.21,65.31,61.64,47.53,46.26,37.70,33.19,17.59,14.28.HRMS(ESI):C25H27NO9H(M+H+)calc.for:486.171708;found:486.171934.
Example 6
Compound M1Synthesis of (Man + Man)
Dissolving compound 5(1.00g, 2.06mmol) and 1-azido-alpha-D-mannopyranose (0.42g, 2.06mmol) in 8mL of methanol, adding cuprous chloride (0.41g, 4.12mmol), stirring at room temperature for 24h, monitoring by TLC until the reaction is complete, filtering to remove insoluble substances, washing with methanol, and passing through silica gel column directly to obtain a pale yellow oil M1(Man + Man)1.07g, yield 58%, which is1H NMR and13c NMR is shown in FIGS. 6 and 7; and 0.43g of compound M' in a yield of 30%, which is1H NMR and13c NMR is shown in FIGS. 8 and 9.
Compound M1:1H NMR(500MHz,D2O)δ=8.04(s,2H),6.69(s,2H),6.16(s,2H),5.36(s,2H),4.27(d,J=4.5Hz,2H),4.18(ddd,J1=21.5Hz,J2=10.0Hz,J3=3.5Hz,7H),3.88(ddd,J1=16.0Hz,J2=13.5Hz,J3=6.5Hz,10H),3.72(d,J=7.0Hz,2H),3.40~3.34(m,2H),3.20(s,2H),3.10(t,J=6.5Hz,5H),2.89(t,J=6.5Hz,4H),1.16~1.12(m,3H).13C NMR(125MHz,D2O)δ=178.97,174.28,146.80,136.43,122.88,87.59,86.81,81.20,78.97,76.21,76.05,75.81,72.39,70.72,69.12,68.48,66.66,65.65,62.36,60.61,47.56,46.33,37.67,32.96,20.29,16.85.HRMS(ESI):C37H49N7O19H(M+H+)calc.for:896.31862;found:896.31631.
A compound M':1H NMR(500MHz,D2O)δ=8.04(s,1H),6.60(s,2H),5.63(d,J=9.0Hz,1H),5.30(s,2H),4.26~4.07(m,8H),3.98(t,J=6.0Hz,1H),3.86(dd,J1=9.5Hz,J2=2.5Hz,1H),3.77(d,J=6.0Hz,4H),3.11(s,2H),3.04(t,J=7.0Hz,2H),2.82(t,J=7.0Hz,2H),2.59(t,J=6.5Hz,2H),2.46(d,J=5.0Hz,2H),2.33(s,1H),1.15(s,3H).13C NMR(125MHz,D2O)δ=177.53,172.94,172.69,172.12,146.40,136.36,122.30,82.23,80.90,76.81,71.08,69.26,68.73,67.02,65.30,61.74,60.86,47.95,47.78,47.61,37.34,32.91,23.01,20.27,16.61,13.68.HRMS(ESI):C31H38N4O14H(M+H+)calc.for:691.24921;found:691.24638.
example 7
Compound M2Synthesis of (Man + β Glu)
Dissolving compound M' (1.00g, 2.06mmol) and 1-azido-beta-D-glucopyranose (0.50g, 2.47mmol) in 8mL of methanol, adding cuprous chloride (0.61g, 6.18mmol), stirring at room temperature for 24h, monitoring by TLC until the reaction is complete, filtering to remove insoluble substances, washing with methanol, and passing through silica gel column directly to obtain a light yellow oil M2(Man +. beta. Glu)1.12g, yield 61%, which1H NMR and13c NMR is shown in FIGS. 10 and 11.
1H NMR(500MHz,D2O)δ=8.05(s,2H),6.63(s,2H),5.72(s,2H),5.30(s,2H),4.17(d,J=31.5Hz,4H),4.01~3.86(m,4H),3.70(dd,J1=41.0Hz,J2=32.0Hz,9H),3.53~3.45(m,2H),3.36(s,2H),3.12(s,2H),3.04(s,4H),2.82(s,3H),1.10(s,3H).13C NMR(125MHz,D2O)δ=179.24,174.48,174.30,147.08,136.72,123.04,86.77,81.11,76.31,70.79,68.60,66.77,65.75,62.42,60.69,47.65,46.42,37.84,33.10,20.36,16.89.HRMS(ESI):C37H49N7O19H(M+H+)calc.for:896.31625;found:896.31489.
Example 8
Compound M3Synthesis of (Man + β Gal)
Reacting compound M1' (1.00g, 2.06mmol) and 1-azido-beta-D-galactopyranose (0.50g, 2.47mmol) were dissolved in 8mL of methanol, followed by addition of cuprous chloride (0.61g, 6.18mmol), stirring at room temperature for 24h, TLC monitoring until the reaction was complete, filtration to remove insoluble material, washing with methanol and passing directly through a silica gel column to give M as a pale yellow oil3(Man +. beta. Gal)1.16g, yield 63%, which1H NMR and13c NMR is shown in FIGS. 12 and 13.
1H NMR(500MHz,D2O)δ=8.06(s,1H),8.00(s,1H),6.65(s,2H),6.12(s,1H),5.74(d,J=9.0Hz,1H),5.32(s,2H),4.24(s,2H),4.12(dd,J1=20.5Hz,J 2=14.5Hz,5H),4.02(s,1H),3.97~3.70(m,10H),3.67(t,J=9.0Hz,1H),3.34(s,1H),3.15(s,2H),3.07(d,J=5.0Hz,4H),2.85(s,4H),1.11(s,3H).13C NMR(125MHz,D2O)δ=178.94,174.20,174.11,146.88,136.50,122.87,86.62,81.00,76.15,70.55,68.43,66.61,65.59,62.27,60.43,60.43,47.50,46.26,37.68,32.87,20.19,16.68.HRMS(ESI):C37H49N7O19H(M+H+)calc.for:896.31921;found:896.31875.
Example 9
ROMP polymerization for preparing sugar-containing polymer of same (different) type without protecting group
In a vacuum glove box, a sugar-containing monomer M (0.1117mmol, M respectively) was weighed1、M2And M3) And Grubbs' third generation catalyst (8.9mg, 0.0100mmol) into a 10mL reaction flask, followed by 1.5mL anhydrous DMF to dissolve completely, stirring at 50 deg.C for 18h, adding 0.1mL vinyl ethyl ether to the reaction flask after the reaction is over, and continuing stirringStirring for 30min, settling the reaction solution in 20mL of methanol solution (repeating for three times) to obtain gray solid, drying in a vacuum drying oven at 60 ℃ to constant weight, weighing, and obtaining the yield of 74-78%.
The prepared sugar polymers respectively correspond to a sugar polymer P (Man + Man), a sugar polymer P (Man + beta Glu) and a sugar polymer P (Man + beta Gal), and the sugar polymers are1H NMR is shown in fig. 14-16, while the corresponding gel chromatogram is shown in fig. 17, and the Gel Permeation Chromatography (GPC) characterization is shown in table 1 below.
The number average molecular weight of the resulting polymer was 7.9X 10 by GPC measurement of the sugar-containing polymer without a protective group3~8.2×103Within the range, the difference with a set value of the molecular weight of 10000 is not large, the molecular weight dispersion width is 1.08-1.10, the PDI value is small, the fluctuation is small, and the molecular weight is controllable, and FIG. 17 is a gel chromatogram of the prepared sugar-containing polymer.
Table 1Characterization of the glycopolymers via GPC
aMolar ratio of[Glycomonomer(M)]/[Grubbs catalyst(G)].bObtained by GPC.cIsolated yield.
Compared with other polymerization methods of sugar-containing derivatives, the invention has the following innovations in the preparation of sugar-containing monomers and polymers:
in example 5:
since compound 5 contains an ester, it is not suitable to introduce a terminal alkyne into the terminal functional group by the conventional Williamson synthesis method, which generates a hydrogen halide to hydrolyze the ester. The invention creatively selects 4-valeric anhydride as an acylating agent, directly introduces terminal alkyne by an esterification method, is suitable for phenolic hydroxyl which is difficult to react or hydroxyl compounds with larger steric hindrance, does not hydrolyze ester, and has the yield as high as 90 percent.
In example 6:
the current CuAAC comparative classical reaction system is the reaction of blue vitriod and sodium ascorbate in a mixed solvent of tert-butyl alcohol and water, but the sodium ascorbate is alkaline, which can hydrolyze ester bonds in compound 5. Therefore, cuprous chloride is selected as a catalyst to react in a methanol solution at normal temperature, the problems that sugar without a protecting group is difficult to dissolve in an organic solvent, and the hydrolysis of ester is inhibited by adding alcohol in a reaction system are solved, so that the sugar monomer without the protecting group and the like (different) is obtained by reacting at room temperature.
In example 9:
because sugar monomers without protecting groups are insoluble in organic solvents, and the protic solvent has a certain inhibiting effect on the activity of Grubbs catalysts, ROMP of sugar monomers without protecting groups in homogeneous solvents is rarely reported. The invention selects a good aprotic solvent, namely N, N' -dimethylformamide, has good solubility, can dissolve sugar monomers without protecting groups, and does not inhibit the activity of the Grubbs catalyst. The sugar-containing polymer of the same type (different type) containing no protecting group with regular structure, controllable molecular weight and narrow molecular weight distribution is prepared by ring-opening metathesis polymerization under the action of Grubbs three-generation catalyst.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.
Claims (10)
1. A method for preparing a protecting group-free iso (iso) saccharide-containing polymer by ROMP polymerization reaction is characterized in that under the atmosphere of inert gas, the protecting group-free iso (iso) saccharide monomer and a Grubbs three-generation catalyst are subjected to ROMP polymerization reaction in an N, N-dimethylformamide solvent to obtain a target product.
2. The method for preparing the sugar-containing polymer of the same (different) type without the protecting group by ROMP polymerization reaction according to claim 1, wherein the temperature of ROMP polymerization reaction is 40-60 ℃ and the reaction time is 12-18 h.
3. The method of claim 1, wherein the molar ratio of the sugar monomer of the sugar of the same (different) type without the protecting group to the Grubbs' tertiary catalyst is 10-15: 1.
4. The method of claim 1, wherein the non-protecting group homo (hetero) saccharide-containing monomer is a α -D-mannose monomer, a β -D-glucose monomer or a β -D-galactose monomer.
5. The method for preparing a protecting group-free sugar-containing polymer of the same (different) type by ROMP polymerization reaction according to claim 1 or 4, wherein the protecting group-free sugar-containing polymer of the same (different) type is prepared by the following method:
(1) reacting furan and maleic anhydride in a solvent at room temperature to generate a compound 1;
(2) reacting the compound 1 with ethanolamine in methanol to generate a compound 2;
(3) reacting the compound 2, TDC, N' -dicyclohexylcarbodiimide and 4-dimethylaminopyridine in dichloromethane to generate a compound 3;
(4) compound 3 and Dowex-H+Reacting the resin at normal temperature to generate a compound 4;
(5) reacting the compound 4, 4-pentanoic anhydride, 4-dimethylamino pyridine and pyridine in dichloromethane to generate a compound 5;
(6) compounds 5 and 1-StackThe nitrogen-alpha-D-mannopyranose is catalyzed by cuprous chloride in methanol at normal temperature to react to generate a compound M1And compound M';
(7) dissolving the compound M' and 1-azido-beta-D-glucopyranose in methanol, adding cuprous chloride as a catalyst, stirring at normal temperature, filtering to remove insoluble substances, washing with methanol, and performing column chromatography to obtain the compound M2;
(8) Dissolving the compound M' and 1-azido-beta-D-galactopyranose in methanol, adding cuprous chloride as catalyst, stirring at normal temperature, filtering to remove insoluble substances, washing with methanol, and performing column chromatography to obtain compound M3;
The resulting Compound M1Compound M2And a compound M3Namely alpha-D-mannose monomer, beta-D-glucose monomer or beta-D-galactose monomer;
the chemical structure of compound M' is as follows:
6. the process for preparing a protecting group-free sugar-containing polymer of the same (different) type by ROMP polymerization as claimed in claim 5, wherein the molar ratio of maleic anhydride to furan in the step (1) is (0.2-0.4): 1, the reaction process is specifically as follows: the reaction was carried out at room temperature for 24 h.
7. The method for preparing a protecting group-free sugar-containing polymer of the same (different) type by ROMP polymerization as claimed in claim 5, wherein the molar ratio of the compound 1 to ethanolamine in the step (2) is (200-): 1, the reaction process is specifically as follows: the mixture was stirred at 0 ℃ for 1 hour and then reacted at room temperature for 1 hour.
8. The process for preparing a protecting group-free sugar-containing polymer of the same (different) type by ROMP polymerization as claimed in claim 5, wherein in the step (3), the mass ratio of the compound 2, TDC, N' -dicyclohexylcarbodiimide and 4-dimethylaminopyridine is (9-12): (8-12): (14-18): 1.6;
the reaction process specifically comprises the following steps: stirred at room temperature for 24 h.
9. The process according to claim 5, wherein the molar ratio of the compound 4, 4-pentanoic anhydride and 4-dimethylaminopyridine in step (5) is 1: (2-4): (0.4-0.6);
the reaction process specifically comprises the following steps: the reaction was stirred at room temperature for 16 h.
10. The method for preparing a protecting group-free sugar-containing polymer of the same (different) type by ROMP polymerization reaction as claimed in claim 5, wherein the molar ratio of the compound 5, 1-azido- α -D-mannopyranose to cuprous chloride in the step (6) is 1: (0.8-1.2): (1.5-2.5);
in the step (7), the molar ratio of the compound M', 1-azido-beta-D-glucopyranose to cuprous chloride is 1: (1.0-1.4): (2.5-3.5);
in the step (8), the molar ratio of the compound M', the 1-azido-beta-D-galactopyranose and the cuprous chloride is 1: (1.0-1.4): (2.5-3.5).
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114773513A (en) * | 2022-04-19 | 2022-07-22 | 上海应用技术大学 | Mannose polymer prepared by ROMP polymerization one-pot method and capable of being recognized by sword bean protein, and preparation method and application thereof |
CN114773415A (en) * | 2022-04-19 | 2022-07-22 | 上海应用技术大学 | Double-arm sugar-containing compound without base protection and preparation method thereof |
CN114773511A (en) * | 2022-04-19 | 2022-07-22 | 上海应用技术大学 | Mannose-containing polymer and preparation method thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108822239A (en) * | 2018-07-10 | 2018-11-16 | 上海应用技术大学 | A kind of method that marriage ROMP polymerization prepares sugar-containing polymer with sulfydryl-alkene addition reaction |
CN108997520A (en) * | 2018-06-07 | 2018-12-14 | 上海应用技术大学 | A kind of norbornene derivative sugar unit containing foreign peoples homopolymer and its synthetic method |
-
2020
- 2020-12-09 CN CN202011425517.7A patent/CN112625220A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108997520A (en) * | 2018-06-07 | 2018-12-14 | 上海应用技术大学 | A kind of norbornene derivative sugar unit containing foreign peoples homopolymer and its synthetic method |
CN108822239A (en) * | 2018-07-10 | 2018-11-16 | 上海应用技术大学 | A kind of method that marriage ROMP polymerization prepares sugar-containing polymer with sulfydryl-alkene addition reaction |
Non-Patent Citations (1)
Title |
---|
上海应用技术大学: "联姻开环易位聚合和CuAAC反应制备异质含糖聚合物及其与凝集素ConA特异性识别研究", 《道客巴巴》 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114773513A (en) * | 2022-04-19 | 2022-07-22 | 上海应用技术大学 | Mannose polymer prepared by ROMP polymerization one-pot method and capable of being recognized by sword bean protein, and preparation method and application thereof |
CN114773415A (en) * | 2022-04-19 | 2022-07-22 | 上海应用技术大学 | Double-arm sugar-containing compound without base protection and preparation method thereof |
CN114773511A (en) * | 2022-04-19 | 2022-07-22 | 上海应用技术大学 | Mannose-containing polymer and preparation method thereof |
CN114773513B (en) * | 2022-04-19 | 2023-09-26 | 上海应用技术大学 | Mannose polymer capable of being identified with canavalin and prepared by utilizing ROMP polymerization one-pot method as well as preparation method and application thereof |
CN114773511B (en) * | 2022-04-19 | 2023-10-31 | 上海应用技术大学 | Mannose-containing polymer and preparation method thereof |
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