CN105273028A - 一种黄酮类化合物5-o-糖苷的制备方法 - Google Patents
一种黄酮类化合物5-o-糖苷的制备方法 Download PDFInfo
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- CN105273028A CN105273028A CN201510815974.XA CN201510815974A CN105273028A CN 105273028 A CN105273028 A CN 105273028A CN 201510815974 A CN201510815974 A CN 201510815974A CN 105273028 A CN105273028 A CN 105273028A
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- Prior art keywords
- full guard
- base
- preparation
- glycosyl
- flavones
- Prior art date
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- -1 flavonoid compound Chemical class 0.000 title claims abstract description 83
- 238000002360 preparation method Methods 0.000 title claims abstract description 43
- 229930003935 flavonoid Natural products 0.000 title claims abstract description 16
- 235000017173 flavonoids Nutrition 0.000 title claims abstract description 16
- 229930003944 flavone Natural products 0.000 claims abstract description 29
- 235000011949 flavones Nutrition 0.000 claims abstract description 29
- 229930182470 glycoside Natural products 0.000 claims abstract description 22
- 238000006206 glycosylation reaction Methods 0.000 claims abstract description 17
- 239000001301 oxygen Substances 0.000 claims abstract description 15
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 14
- 125000003147 glycosyl group Chemical group 0.000 claims abstract description 13
- 229940125904 compound 1 Drugs 0.000 claims abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 150000002213 flavones Chemical class 0.000 claims description 24
- 239000002808 molecular sieve Substances 0.000 claims description 12
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical group [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 11
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 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 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 230000002378 acidificating effect Effects 0.000 claims description 8
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims description 6
- 230000032050 esterification Effects 0.000 claims description 6
- 238000005886 esterification reaction Methods 0.000 claims description 6
- 238000005554 pickling Methods 0.000 claims description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 5
- WQZGKKKJIJFFOK-DVKNGEFBSA-N alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-DVKNGEFBSA-N 0.000 claims description 5
- 125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 claims description 4
- 229910003771 Gold(I) chloride Inorganic materials 0.000 claims description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- SRBFZHDQGSBBOR-KLVWXMOXSA-N beta-L-arabinopyranose Chemical compound O[C@H]1CO[C@H](O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-KLVWXMOXSA-N 0.000 claims description 4
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 claims description 4
- FDWREHZXQUYJFJ-UHFFFAOYSA-M gold monochloride Chemical compound [Cl-].[Au+] FDWREHZXQUYJFJ-UHFFFAOYSA-M 0.000 claims description 4
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical compound OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 claims description 3
- WIHIUTUAHOZVLE-UHFFFAOYSA-N 1,3-diethoxypropan-2-ol Chemical compound CCOCC(O)COCC WIHIUTUAHOZVLE-UHFFFAOYSA-N 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims description 2
- 239000002841 Lewis acid Substances 0.000 claims description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- WQZGKKKJIJFFOK-PQMKYFCFSA-N alpha-D-mannose Chemical compound OC[C@H]1O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-PQMKYFCFSA-N 0.000 claims description 2
- HMFHBZSHGGEWLO-AIHAYLRMSA-N alpha-D-ribose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-AIHAYLRMSA-N 0.000 claims description 2
- SRBFZHDQGSBBOR-LECHCGJUSA-N alpha-D-xylose Chemical compound O[C@@H]1CO[C@H](O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-LECHCGJUSA-N 0.000 claims description 2
- SHZGCJCMOBCMKK-SXUWKVJYSA-N alpha-L-fucose Chemical compound C[C@@H]1O[C@@H](O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-SXUWKVJYSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-RWOPYEJCSA-N beta-D-mannose Chemical compound OC[C@H]1O[C@@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-RWOPYEJCSA-N 0.000 claims description 2
- HMFHBZSHGGEWLO-TXICZTDVSA-N beta-D-ribose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-TXICZTDVSA-N 0.000 claims description 2
- SHZGCJCMOBCMKK-KGJVWPDLSA-N beta-L-fucose Chemical compound C[C@@H]1O[C@H](O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-KGJVWPDLSA-N 0.000 claims description 2
- 229940017687 beta-d-ribose Drugs 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- 229910000366 copper(II) sulfate Inorganic materials 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 239000003446 ligand Substances 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 claims description 2
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 2
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000000969 xylosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)CO1)* 0.000 claims description 2
- 230000013595 glycosylation Effects 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 229910052799 carbon Inorganic materials 0.000 abstract description 2
- 238000007086 side reaction Methods 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 abstract 5
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 abstract 5
- 150000002212 flavone derivatives Chemical class 0.000 abstract 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- 238000005858 glycosidation reaction Methods 0.000 abstract 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 31
- IYRMWMYZSQPJKC-UHFFFAOYSA-N kaempherol Natural products C1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 IYRMWMYZSQPJKC-UHFFFAOYSA-N 0.000 description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- UBSCDKPKWHYZNX-UHFFFAOYSA-N Demethoxycapillarisin Natural products C1=CC(O)=CC=C1OC1=CC(=O)C2=C(O)C=C(O)C=C2O1 UBSCDKPKWHYZNX-UHFFFAOYSA-N 0.000 description 21
- 235000008777 kaempferol Nutrition 0.000 description 21
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 21
- 239000002585 base Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 15
- 238000010189 synthetic method Methods 0.000 description 14
- 229930182478 glucoside Natural products 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- REFJWTPEDVJJIY-UHFFFAOYSA-N quercetin Natural products C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 11
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 9
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 9
- 235000005875 quercetin Nutrition 0.000 description 9
- 229960001285 quercetin Drugs 0.000 description 9
- 238000003756 stirring Methods 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 0 *C(c1ccccc1C#C*)=O Chemical compound *C(c1ccccc1C#C*)=O 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 125000003550 alpha-D-galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 229930182486 flavonoid glycoside Natural products 0.000 description 2
- 150000007955 flavonoid glycosides Chemical class 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
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- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
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- 230000000844 anti-bacterial effect Effects 0.000 description 1
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- 230000007547 defect Effects 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
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- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
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- 210000004185 liver Anatomy 0.000 description 1
- LRDGATPGVJTWLJ-UHFFFAOYSA-N luteolin Natural products OC1=CC(O)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 LRDGATPGVJTWLJ-UHFFFAOYSA-N 0.000 description 1
- 235000009498 luteolin Nutrition 0.000 description 1
- IQPNAANSBPBGFQ-UHFFFAOYSA-N luteolin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C(O)=C1 IQPNAANSBPBGFQ-UHFFFAOYSA-N 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 description 1
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 description 1
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Classifications
-
- 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
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Abstract
本发明公开了一种黄酮类化合物5-O-糖苷1的制备方法,包含下列步骤:将黄酮化合物受体2和糖基炔酯给体3进行糖苷化反应,即可制得黄酮5-O-糖苷化产物1;
Description
技术领域
本发明涉及一种黄酮类化合物5-O-糖苷的制备方法
背景技术
黄酮类化合物是在植物中分布非常广泛的一类天然产物,其在植物的生长,发育,开花,结果及防菌防病等方面都起着非常重要的作用。其典型代表包括水飞蓟宾(保肝),木犀草素(抗菌),染料木素(抗HIV),黄柏苷(抗癌),葛根素(扩冠)等。因此,这类化合物具有非常广阔的药物开发前景。
黄酮5-O-糖苷的及黄酮醇类化合物是其中一类重要的天然产物黄酮苷,它广泛存在于自然界中,且表现出很好的抗糖尿病活性(DengY.-L.Biol.Pharm.Bull.2007,30,1123;Miyakoshi,M.Nat.Med.2005,59,113;Whiters,S.G.ChemBioChem2008,9,433.),因而具有良好的要用前景。而由于分子内氢键的存在,构建5位羟基的糖苷键一直是黄酮苷合成中的一个难点,目前只有少数几位化学家完成了黄酮化合物5-O-糖苷的合成[(a)Schmidt,R.R.Synthesis,1993,325.(b)Alluis,B.Helv.Chim.Acta,2001,84,1133.(c)Kajjout,M.Tetrahedron,2011,67,4731.]。但这几种方法均具有产率低,适用范围窄的缺点。
发明内容
本发明为了克服现有的黄酮5-O-糖苷的制备方法中,产率低下,适用糖基种类有限等缺陷,提供一种黄酮类化合物5-O-糖苷的制备方法。
本发明的制备方法可适用于制备不同糖基取代的黄酮5-O-糖苷化合物,且反应条件温和,绿色环保,产物的产率和纯度较高。
本发明是通过以下步骤来实现的:
将黄酮受体2和糖基炔酯给体3进行糖苷化反应,即可制得黄酮5-O-糖苷化合物1;
其中,R1为本领域常用的羟基保护基,所述的保护基较佳的为苄基(Bn),己酰基,叔丁基二甲基硅基(TBS);
R2为H或者OR’,其中R’为本领域常用的羟基保护基,所述的保护基较佳的为苄基(Bn),己酰基,叔丁基二甲基硅基(TBS);
R3为全保护的β-D-葡萄糖基、全保护的α-D-葡萄糖基、全保护的β-D-半乳糖基、全保护的α-D-半乳糖基、全保护的β-D-甘露糖基、全保护的α-D-甘露糖基、全保护的β-D-木糖基、全保护的α-D-木糖基、全保护的β-D-2-氨基葡萄糖基、全保护的α-D-2-氨基葡萄糖基、全保护的α-L-鼠李糖基、全保护的β-L-鼠李糖基、全保护的α-D-核糖基、全保护的β-D-核糖基、全保护的α-L-核糖基、全保护的β-L-核糖基、全保护的α-D-阿拉伯糖基、全保护的β-D-阿拉伯糖基、全保护的α-L-阿拉伯糖基、全保护的β-L-阿拉伯糖基、全保护的α-L-岩藻糖基、全保护的β-L-岩藻糖基、全保护的β-D-葡萄糖醛酸基、全保护的α-D-葡萄糖醛酸基、全保护的β-D-半乳糖醛酸基、或者全保护的α-D-半乳糖醛酸基;其中糖上的保护基为乙酰基、苯甲酰基或苄基;
R4表示未取代、单取代、二取代、三取代或四取代,R4为H、甲氧基、乙氧基、甲硫基、乙硫基、二甲氨基、二乙氨基、N3、CN、NO2基、三氟甲基和三氯甲基中的一种或多种;
R5为H、甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、环丙基、环丁基、环戊基、环己基、苯基、对甲氧基苯基、对硝基苯基、邻甲氧基苯基或邻硝基苯基。
本发明中,R3优选为全保护的β-D-葡萄糖基、全保护的α-D-葡萄糖基、全保护的β-D-半乳糖基、全保护的α-D-半乳糖基、全保护的α-L-鼠李糖基、全保护的β-L-鼠李糖基;其中糖上的保护基优选为苯甲酰基。
本发明中,所述的“全保护的……糖基”是指糖基上的羟基均被本领域常规的羟基保护基(如苯甲酰基)保护起来的糖基。
本发明中,所述的制备黄酮5-位氧苷化合物1的糖苷化反应的方法和条件可为本领域类似的糖苷化反应的常规方法和条件,本发明特别优选下述方法和条件:有机溶剂中,惰性气体保护下,在亲炔基路易斯酸的作用下,将黄酮受体2和糖基炔酯给体3进行糖苷化反应,即可。
其中,所述的有机溶剂可为本领域所用的常规溶剂,较佳的为干燥的有机溶剂,最好为新蒸溶剂,如二氯甲烷、甲苯、硝基甲烷和乙腈中的一种或多种,更佳的为干燥的二氯甲烷。有机溶剂与黄酮受体2的体积质量比较佳的为2~10ml/mmol,更佳为3ml/mmol。
所述的惰性气体较佳的为干燥的惰性气体,如高纯氩气和/或高纯氮气。
所述的亲炔基路易斯酸较佳的为AuCl、AuCl3、AuLOTf、AuLNTf、HgOTf和PtCl2中的一种或多种,其中,L为本领域常规的膦配体,如三丁基膦、三乙基膦、三苯基膦或三金刚烷基膦,优选三苯基膦。所述的亲炔基路易斯酸的用量较佳的为糖基炔酯给体3的摩尔量的0.001~1倍,更佳的为0.2倍。
所述的制备黄酮5-O-糖苷化合物1的糖苷化反应的温度较佳的为0~80℃,更佳的为30℃。所述的糖苷化反应的时间,一般为2~24小时,更佳的为4小时。
所述的制备黄酮5-位氧苷化合物1的糖苷化反应在干燥剂的存在下进行,所述的干燥剂较佳的为分子筛、分子筛、分子筛、酸洗的分子筛、酸洗的分子筛、酸洗的分子筛、无水硫酸钠、无水硫酸钙、无水硫酸铜和无水硫酸镁中的一种或多种。干燥剂的用量较佳的为黄酮受体2的摩尔量的1.0~4.0倍,更佳的为2.0倍。
本发明中,所述的糖基炔酯给体3由下列方法制得:将化合物R3OH和化合物4进行酯化反应,即可;
其中,各基团的定义均同前所述。
所述的酯化反应的方法和条件均可为本领域此类反应的常规方法和条件,例如,可参照文献(Li,Y.;Yang,Y.;Yu,B.TetrahedronLett.2008,49,3604)的方法进行。本发明特别优选下述方法和条件:有机溶剂中,在惰性气体的保护下,在碱和脱水剂的作用下,将化合物R3OH和炔酸4进行酯化反应,即可。
其中,所述的有机溶剂可为本领域此类反应所用的常规溶剂,较佳的为干燥的有机溶剂,最好为新蒸溶剂,如二氯甲烷、甲苯、硝基甲烷和乙腈中的一种或多种,更佳的为二氯甲烷。有机溶剂与异头位裸露的糖R3OH的体积质量比较佳的为2~10mL/mmol,更佳为5mL/mmol。
所述的惰性气体较佳的为干燥的惰性气体,如高纯氩气和/或高纯氮气。
所述的碱可为本领域此类反应所用的常规碱,较佳的为DMAP和二异丙基乙基胺。其与异头位裸露的糖R1OH的摩尔比较佳的为0.1~3当量,更佳的为1.2当量。
所述的脱水剂可为本领域此类反应所用的常规脱水剂,较佳的为DCC和/或EDC。脱水剂的用量可为常规用量,其与异头位裸露的糖基R3OH的摩尔比较佳的为1:1.5~5.0。
所述的异头位裸露的糖R3OH与炔酸4的摩尔比较佳的为1:1.5~5.0,更佳的为2.0当量。
所述的酯化反应的温度较佳的为0~80℃,更佳的为30℃。所述的酯化反应的时间一般为2~6小时。
本发明的制备方法中,上述各优选技术特征可任意组合,即得本发明的各较佳实例。
本发明的技术效果是:本发明是一种高效、易于操作、绿色环保、底物适用范围广的合成黄酮5-位氧苷化合物1的方法,并且该方法在合成黄酮5-位氧苷化合物及类似物时,具有很好的区域选择性,即将糖基选择性引入到5位,无6位碳糖苷化副反应发生,因此本发明的制备方法的发现将有利于黄酮5-位氧苷化合物的开发利用。
具体实施方式
下面将结合实施例1—11详细说明本发明所具有的有益效果,旨在帮助阅读者更好地理解本发明的实质,但不能对本发明的实施和保护范围构成任何限定。
下述各实施例中涉及到的室温为20~35℃。
实施例1
3,7,4'-三-O-叔丁基二甲基硅基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-葡萄糖)山奈酚糖苷的制备
步骤1:全苯甲酰基保护的葡萄糖给体的合成:
氮气保护下,将异头位裸露的全Bz保护的葡萄糖(5g,8.4mmol)及邻炔基苯甲酸(1.87g,10.1mmol)溶于干燥的DCM(10mL)中,然后向体系中加入EDCI(2g,10.1mmol),DMAP(1g,10mmol)和DIPEA(3ml,16.7mmol),并于室温下搅拌3h,TLC跟踪至反应结束。将反应体系减压浓缩粗产品,然后柱层析得葡萄糖炔酯给体(6.1g,95%);
步骤2:3,7,4'-三-O-叔丁基二甲基硅基山奈酚的制备
氮气保护下,将山奈酚(2g,7mmol)和TBSCl(4.2g,28mmol)溶于干燥的DMF(5mL)中,室温反应,TLC跟踪至反应结束。将反应体系用DCM萃取,水洗涤,再依次用饱和食盐水洗涤,无水硫酸钠干燥。所得滤液减压浓缩后柱色谱分离得目标产物(3.6g,81%);
步骤3:3,7,4'-三-O-叔丁基二甲基硅基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-葡萄糖)山奈酚糖苷的制备
氮气保护下,将全苯甲酰基保护的葡萄糖给体(115mg,0.15mmol)和3,7,4'-三叔丁基二甲基硅基山奈酚(62mg,0.1mmol)溶于干燥的DCM(3mL)中,反应体系在室温下搅拌30min后,加入Ph3PAuNTf2(22mg,0.03mmol),室温搅拌直至反应完全。反应体系减压浓缩后得粗产品,柱层析纯化得目标产物(103mg,90%)
(c1.0,CHCl3);1HNMR(400MHz,CDCl3)δ8.07(d,J=7.32Hz,2H),7.93-7.87(m,6H),7.82(d,J=8.64Hz,2H),7.52-7.28(m,12H),6.91(d,J=8.68Hz,2H),6.62-6.60(m,2H),6.04-5.95(m,2H),5.86(t,J=9.4Hz,1H),5.71(d,J=6.92Hz,1H),4.61(dd,J=3.1,12.2Hz,1H),4.50(dd,J=4.6,12.0Hz,1H),4.23-4.20(m,1H),1.00(s,9H),0.95(s,9H),0.75(s,9H),0.23(s,6H),0.22(s,3H),0.21(s,3H),0.01(s,3H),0(s,3H);13CNMR(100MHz,CDCl3)δ172.5,166.0,165.8,165.2,165.1,159.3,157.6,157.1,155.9,149.5,137.7,133.0,130.1,129.8,129.7,128.4,128.3,128.1,119.8,110.8,109.7,103.9,99.9,77.3,77.2,77.0,76.7,73.1,72.5,72.0,69.6,65.5,63.0,29.7,25.8,25.7,25.5,18.7,18.3,18.2,1.0,-3.9,-4.0,-4.4;HRMS(ESI)calcdforC67H78O15Si3Na+:1229.4541,Found:1229.4542。
实施例2
3,7,4'-三-O-苄基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-葡萄糖)山奈酚糖苷的制备
步骤1:如实施例1步骤1所示;
步骤2:3,7,4'-三-O-苄基山奈酚的制备
氮气保护下,将山奈酚(4.2g,15mmol)和溴化苄(5.7ml,48mmol)溶于干燥的DMF(20mL)中,再加入碳酸钾粉末(7.3g,53mmol)。室温反应,TLC跟踪至反应结束。将反应体系用DCM萃取,水洗涤,再依次用饱和食盐水洗涤,无水硫酸钠干燥。所得滤液减压浓缩后柱色谱分离得目标产物(6g,72%)。1HNMR(400MHz,CDCl3)δ12.74(s,1H),8.00(d,J=8.7Hz,2H),7.46-7.26(m,15H),7.04(d,J=9.0Hz,2H),6.51(d,J=2.2Hz,1H),6.45(d,J=2.2Hz,1H),5.15(s,2H),5.13(s,2H),5.06(s,2H);13CNMR(100MHz,CDCl3)δ178.7,164.4,162.0,160.7,156.7,156.6,137.3,136.4,136.3,135.7,128.71,128.66,128.6,127.4,123.0,114.6,106.1,98.5,93.0,77.3,77.0,76.7,74.2,70.4,70.0;HRMS(ESI)calcdforC36H29O6 +:557.1959,Found:557.1963;
步骤3:3,7,4'-三-O-叔丁基二甲基硅基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-葡萄糖)山奈酚糖苷的制备
氮气保护下,将全苯甲酰基保护的葡萄糖给体(115mg,0.15mmol)和3,7,4'-三苄基山奈酚(56mg,0.1mmol)溶于干燥的DCM(3mL)中,反应体系在室温下搅拌30min后,加入Ph3PAuNTf2(22mg,0.03mmol),室温搅拌直至反应完全。反应体系减压浓缩后得粗产品,柱层析纯化得目标产物(108mg,87%)。(c1.0,CHCl3);1HNMR(400MHz,CDCl3)δ8.1(d,J=7.4Hz,2H),7.97-7.89(m,8H),7.53-7.20(m,27H),6.99(d,J=9.0Hz,2H),6.84(d,J=2.3Hz,1H),6.64(d,J=2.3Hz,1H),6.07-5.96(m,2H),5.86(t,J=9.4Hz,1H),5.70(d,J=7.1Hz,1H),5.12(s,2H),5.07(s,2H),4.77(d,J=12.4Hz,1H),4.72(dd,J=2.9,12.2Hz,1H),4.67(d,J=10.8Hz,1H),4.52(dd,J=5.4,12.3Hz,1H),4.31-4.27(m,1H);13CNMR(100MHz,CDCl3)δ172.7,166.0,165.8,165.3,165.2,162.0,160.2,157.8,156.6,153.3,139.2,137.0,136.4,135.6,133.4,133.1,132.9,132.7,128.8,128.7,128.6,128.0,127.44,127.42,123.4,111.5,111.0,104.7,100.2,97.6,77.3,77.0,76.7,73.3,72.8,72.6,71.8,70.4,70.0,69.5,62.9。
实施例3
3,7,4'-三-O-己酰基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-葡萄糖)山奈酚糖苷的制备
步骤1:合成方法如实施例1步骤1所示;
步骤2:3,7,4'-三-O-己酰基山奈酚的制备
氮气保护下,将山奈酚(2.3g,8mmol)和己酰氯(3.7ml,26.4mmol)溶于干燥的丙酮(100mL)中,再加入三乙胺(3.65ml,26.4mmol)。室温反应,TLC跟踪至反应结束。将反应体系减压浓缩后柱色谱分离得目标产物(2.8g,61%)。1HNMR(400MHz,CDCl3)δ12.18(s,1H),7.89(dd,J=2.0,7.0Hz,2H),7.28(dd,J=1.9,6.9Hz,2H),6.86(d,J=2Hz,1H),6.60(d,J=2Hz,1H),2.65-2.58(m,6H),1.79-1.76(m,6H),1.52-1.41(m,12H),0.97-0.90(m,9H);13CNMR(100MHz,CDCl3)δ176.3,171.7,171.1,170.6,161.7,156.5,156.4,156.0,153.2,132.0,129.7,126.7,122.0,108.7,105.4,101.1,77.3,77.0,76.7,34.3,33.7,31.2,31.14,31.10,24.5,24.42,24.36,22.27,22.25,22.2,13.9,13.8;HRMS(ESI)calcdforC33H40O9Na+:603.2565,Found:603.2562;
步骤3:3,7,4'-三-O-己酰基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-葡萄糖)山奈酚糖苷的制备
氮气保护下,将全苯甲酰基保护的葡萄糖给体(115mg,0.15mmol)和3,7,4'-三己酰基山奈酚(58mg,0.1mmol)溶于干燥的DCM(3mL)中,反应体系在室温下搅拌30min后,加入Ph3PAuNTf2(22mg,0.03mmol),室温搅拌直至反应完全。反应体系减压浓缩后得粗产品,柱层析纯化得目标产物(115mg,99%)。(c1.3,CHCl3);1HNMR(400MHz,CDCl3)δ8.01-7.90(m,8H),7.80(d,J=8.8Hz,2H),7.54-7.30(m,12H),7.21(d,J=8.8Hz,2H),7.09(d,J=2.1Hz,1H),6.96(d,J=2.1Hz,1H),6.03(t,J=9.0Hz,1H),5.95(dd,J=7.1,8.9Hz,1H),5.82(t,J=9.4Hz,1H),5.64(d,J=7.1Hz,2H),4.73(dd,J=3.1,12.2Hz,1H),4.50(dd,J=5.5,12.2Hz,1H),4.33-4.29(m,1H),2.60(t,J=7.4Hz,2H),2.46-2.41(m,4H),1.79-1.62(m,6H),1.43-1.29(m,12H),0.95-0.89(m,9H);13CNMR(100MHz,CDCl3)δ171.7,170.9,170.4,169.4,166.0,165.8,165.1,157.1,159.5,154.2,153.3,152.7,133.4,133.2,133.0,132.7,130.0,129.94,129.88,129.7,129.5,129.4,128.9,128.8,128.4,128.31,128.27,128.0,121.8,113.8,109.5,106.5,100.0,77.3,77.0,76.7,72.7,71.7,69.4,62.9,34.3,34.2,33.7,31.2,31.1,24.5,24.28,24.25,22.3,13.9;HRMS(ESI)calcdforC67H66O18Na+:1181.4141,Found:1181.4148。
实施例4
3,7,3',4'-四-O-叔丁基二甲基硅基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-葡萄糖)槲皮素糖苷的制备
步骤1:合成方法如实施例1步骤1所示;
步骤2:3,7,3',4'-四-O-叔丁基二甲基硅基槲皮素的制备
氮气保护下,将槲皮素(2g,6.6mmol)和TBSCl(5g,33mmol)溶于干燥的DMF(5mL)中,室温反应,TLC跟踪至反应结束。将反应体系用DCM萃取,水洗涤,再依次用饱和食盐水洗涤,无水硫酸钠干燥。所得滤液减压浓缩后柱色谱分离得目标产物(4.3g,85%)。1HNMR(400MHz,CDCl3)δ12.68(s,1H),7.46(d,J=8.4Hz,1H),7.35(s,1H),6.91(d,J=8.4Hz,1H),6.33(s,1H),6.27(d,J=2Hz,1H),1.01(s,9H),1.00(s,9H),0.99(s,9H),0.84(s,9H),0.26(s,6H),0.24(s,6H),0.21(s,6H),0.12(s,6H);13CNMR(100MHz,CDCl3)δ178.2,161.80,161.76,156.4,153.3,149.2,146.8,135.6,124.4,123.2,121.8,120.8,106.1,102.9,98.2,77.3,77.0,76.7,25.94,25.92,25.7,25.6,18.6,18.4,18.2,-4.0,-4.1,-4.2,-4.4;HRMS(ESI)calcdforC39H67O7Si4 +:759.3958,Found:759.3959;
步骤3:3,7,3',4'-四-O-叔丁基二甲基硅基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-葡萄糖)槲皮素糖苷的制备
合成方法如实施例1步骤3所示:97%,(c1.7,CHCl3);1HNMR(400MHz,CDCl3)δ8.08(d,J=7.2Hz,2H),7.92-7.87(m,6H),7.51-7.30(m,13H),6.88(d,J=8.4Hz,1H),6.62(d,J=2.2Hz,1H),6.56(d,J=2.3Hz,1H),6.04-5.93(m,2H),5.85(t,J=9.5Hz,1H),5.71(d,J=7.2Hz,1H),4.60(dd,J=3.3,12.2Hz,1H),4.49(dd,J=4.8,12.2Hz,1H),4.22-4.17(m,1H),1.00(s,9H),0.99(s,9H),0.94(s,9H),0.73(s,9H),0.223(s,3H),0.218(s,3H),0.21(s,3H),0.20(s,6H),0.197(s,3H),-0.01(s,3H),-0.02(s,3H);13CNMR(100MHz,CDCl3)δ172.6,166.0,165.8,165.2,165.1,159.3,157.5,155.9,149.6,148.6,146.6,137.7,133.0,130.1,129.83,129.80,129.7,129.6,128.35,128.25,128.1,123.0,121.4,120.7,110.9,109.9,103.9,100.0,77.3,77.0,76.7,73.0,72.4,72.0,69.6,62.9,25.9,25.7,25.5,18.7,18.5,18.4,18.2,-4.0,-4.07,-4.1,-4.21,-4.25,-4.41,-4.44;HRMS(ESI)calcdforC73H92O16Si4Na+:1359.5355,Found:1359.5361。
实施例5
3,7,3',4'-四-O-叔丁基二甲基硅基-5-O-(2,3,4-三-O-苯甲酰基-α-L-鼠李糖)槲皮素糖苷的制备
步骤1:全苯甲酰基保护鼠李糖给体的制备:
氮气保护下,将异头位裸露的全Bz保护的鼠李糖(5g,10.5mmol)及邻炔基苯甲酸(2.3g,12.6mmol)溶于干燥的DCM(12mL)中,然后向体系中加入EDCI(2.3g,11.6mmol),DMAP(1.2g,11.6mmol)和DIPEA(3.5ml,19.5mmol),并于室温下搅拌3h,TLC跟踪至反应结束。将反应体系减压浓缩粗产品,然后柱层析得鼠李糖炔酯给体(6.1g,93%);
步骤2:合成方法如实施例4步骤2所示;
步骤3:3,7,3',4'-四-O-叔丁基二甲基硅基-5-O-(2,3,4-三-O-苯甲酰基-α-L-鼠李糖)槲皮素糖苷的制备
氮气保护下,将全苯甲酰基保护的鼠李糖给体(97mg,0.15mmol)和3,7,3',4'-四叔丁基二甲基硅基槲皮素(76mg,0.1mmol)溶于干燥的DCM(3mL)中,反应体系在室温下搅拌30min后,加入Ph3PAuNTf2(22mg,0.03mmol),室温搅拌直至反应完全。反应体系减压浓缩后得粗产品,柱层析纯化得目标产物(120mg,99%)。(c1.9,CHCl3);1HNMR(400MHz,CDCl3)δ8.17(d,J=7.32Hz,2H),8.04(d,J=7.4Hz,2H),7.88(d,J=7.32Hz,2H),7.64(t,J=7.36Hz,1H),7.56-7.24(m,10H),6.92(d,J=8.4Hz,1H),6.58(dd,J=2,13.4Hz,1H),6.52(dd,J=3.4,10.4Hz,1H),6.12-6.11(m,1H),5.89(s,1H),5.81(t,J=10.0Hz,1H),4.57-4.50(m,1H),1.33(d,J=6.2Hz,3H),1.02(s,9H),1.01(s,18H),0.83(s,9H),0.33(s,3H),0.29(s,6H),0.28(s,3H),0.24(s,6H),0.23(s,6H);13CNMR(100MHz,CDCl3)δ172.8,166.0,165.5,164.9,159.7,157.9,155.6,149.2,148.6,146.6,138.0,133.4,133.2,130.0,129.9,129.7,129.6,129.4,128.6,128.3,128.1,123.0,121.3,120.7,110.3,105.2,102.4,96.1,77.3,77.2,77.0,76.7,72.0,70.7,69.7,68.2,29.7,26.0,25.9,25.6,19.0,18.6,18.5,18.3,17.7,-3.5,-3.6,-4.06,-4.07,-4.2,-4.3,-4.4;HRMS(ESI)calcdforC66H89O14Si4Na+:1217.5324,Found:1217.5314。
实施例6
3,7,4'-三-O-苄基-5-O-(2,3,4-三-O-苯甲酰基-α-L-鼠李糖)山奈酚糖苷的制备
步骤1:合成方法如实施例5步骤1所示;
步骤2:合成方法如实施例2步骤2所示;
步骤3:3,7,4'-三-O-苄基-5-O-(2,3,4-三-O-苯甲酰基-α-L-鼠李糖)槲皮素糖苷的制备:
合成方法如实施例1步骤3所示:96%,(c0.64,CHCl3);1HNMR(400MHz,CDCl3)δ8.16(d,J=7.5Hz,2H),8.05(d,J=7.5Hz,2H),7.99(d,J=8.4Hz,2H),7.89(d,J=7.5Hz,2H),7.51-7.35(m,24H),7.03(d,J=8.4Hz,2H),6.80(s,1H),6.72(s,1H),6.42(d,J=10.3Hz,2H),6.13(s,1H),5.92(s,1H),5.84(t,J=9.8Hz,1H),5.21-5.10(m,6H),4.61-4.57(m,1H),1.36(d,J=5.9Hz,3H);13CNMR(100MHz,CDCl3)δ173.2,166.0,165.5,165.2,162.4,160.2,158.4,156.2,153.7,133.5,133.2,130.2,130.0,129.9,129.7,129.1,128.7,128.65,128.58,128.4,128.2,128.1,127.9,127.51,127.46,123.5,114.6,110.7,101.4,96.6,96.5,77.3,77.0,76.7,74.0,71.9,70.7,70.5,70.0,69.9,68.4,17.7;HRMS(ESI)calcdforC63H50O13Na+:1037.3144,Found:1037.3140。
实施例7
3,7,4'-三-O-己酰基-5-O-(2,3,4-三-O-苯甲酰基-α-L-鼠李糖)山奈酚糖苷的制备
步骤1:合成方法如实施例5步骤1所示;
步骤2:合成方法如实施例3步骤2所示;
步骤3:3,7,4'-三-O-己酰基-5-O-(2,3,4-三-O-苯甲酰基-α-L-鼠李糖)山奈酚糖苷的制备:
合成方法如实施例1步骤3所示:82%,(c0.9,CHCl3);1HNMR(400MHz,CDCl3)δ8.15(d,J=7.4Hz,2H),8.04(d,J=7.5Hz,2H),7.90-7.86(m,4H),7.52-7.24(m,11H),7.10(d,J=1.8Hz,1H),6.94(d,J=1.8Hz,1H),6.36(dd,J=3.32,10.12Hz,1H),6.05(s,1H),5.89(s,1H),5.81(t,J=9.96,1H),4.44-4.37(m,1H),2.68-2.57(m,6H),1.80-1.75(m,6H),1.41-1.22(m,14H),0.96-0.83(m,9H);13CNMR(100MHz,CDCl3)δ171.7,171.0,170.98,170.0,165.9,165.4,165.0,157.6,156.1,154.6,153.6,152.8,134.3,133.5,133.2,132.9,129.9,3,129.90,129.7,129.52,129.46,129.33,129.26,128.6,128.3,128.2,127.1,121.9,113.1,105.7,105.4,96.3,77.3,77.2,77.0,76.7,71.7,70.6,69.7,68.3,34.3,33.9,31.19,31.15,31.14,24.5,24.41,24.37,22.3,22.2,13.9,13.83,13.81;HRMS(ESI)calcdforC60H62O16Na+:1061.3930,Found:1061.3930。
实施例8
3,7,4'-三-O-叔丁基二甲基硅基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-半乳糖)山奈酚糖苷的制备
合成方法如实施例1所示:99%,(c1.6,CHCl3);1HNMR(400MHz,CDCl3)δ8.13(d,J=7.4Hz,2H),8.06(d,J=7.3Hz,2H),7.94(d,J=7.4Hz,2H),7.84(d,J=7.3Hz,2H),7.65-7.24(m,14H),6.88(d,J=8.4Hz,1H),6.70(d,J=2.2Hz,1H),6.58(d,J=2.4Hz,1H),6.25(dd,J=3.4,8.4Hz,1H),4.44-4.40(m,2H),1.00(s,9H),0.99(s,9H),0.98(s,9H),0.72(s,9H),0.26(s,3H),0.256(s,3H),0.22(s,6H),0.20(s,6H),0.03(s,3H),-0.12(s,3H);13CNMR(100MHz,CDCl3)δ172.6,165.9,165.6,165.3,159.4,157.6,156.3,149.6,148.6,146.6,137.7,133.21,133.18,130.1,130.08,129.8,129.7,128.6,128.4,128.36,128.3,128.1,110.8,109.3,103.7,100.6,77.3,77.0,76.7,71.9,71.6,69.5,68.0,61.8,25.9,25.7,25.6,18.7,18.6,18.5,18.3,-4.1,-4.19,-4.23,-4.30,-4.33。
实施例9
3,7,3',4'-四-O-叔丁基二甲基硅基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-半乳糖)槲皮素糖苷的制备
合成方法如实施例4所示:70%,(c1.5,CHCl3);1HNMR(400MHz,CDCl3)δ8.13(d,J=7.4Hz,2H),8.06(d,J=7.3Hz,2H),7.94(d,J=7.4Hz,2H),7.84(d,J=7.3Hz,2H),7.65-7.24(m,14H),6.88(d,J=8.4Hz,1H),6.70(d,J=2.2Hz,1H),6.58(d,J=2.4Hz,1H),6.25(dd,J=8.0,10.3Hz,1H),6.07(d,J=3.3Hz,1H),5.70(dd,J=3.4,10.4Hz,1H),5.65(d,J=7.9Hz,1H),4.66(dd,J=3.4,8.4Hz,1H),4.44-4.40(m,2H),1.00(s,9H),0.98(s,9H),0.74(s,9H),0.26(s,6H),0.23(s,6H),0.07(s,3H),-0.10(s,3H);13CNMR(100MHz,CDCl3)δ172.5,165.9,165.6,165.3,159.4,157.6,157.1,156.4,149.5,137.7,130.2,130.1,129.8,129.7,128.6,128.4,128.3,128.1,119.8,110.7,109.1,103.8,100.6,77.3,77.0,76.7,71.9,71.6,69.4,68.0,61.7,25.8,25.7,25.6,18.7,18.29,18.26,-3.9,-4.1,-4.31,-4.34,-4.4。
实施例10
3,7,4'-三-O-苄基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-半乳糖)山奈酚糖苷的制备
合成方法如实施例2所示:99%,(c1.8,CHCl3);1HNMR(400MHz,CDCl3)δ8.15(d,J=7.3Hz,2H),8.05(d,J=7.3Hz,2H),8.00(d,J=7.3Hz,2H),7.91(d,J=8.9Hz,2H),7.86(d,J=7.3Hz,2H),7.64-7.14(m,27H),6.98(d,J=9Hz,2H),6.95(d,J=2.3Hz,1H),6.68(d,J=2.3Hz,1H),6.34(dd,J=8.0,10.3Hz,1H),6.08(d,J=2.9Hz,1H),5.7(dd,J=3.4,10.4Hz,1H),5.60(d,J=8.0Hz,1H),5.11(s,2H),5.09(s,2H),4.71(dd,J=6.8,11.2Hz,1H),4.63(d,J=10.7Hz,1H),4.56(d,J=10.4Hz,1H),4.51-4.45(m,2H);13CNMR(100MHz,CDCl3)δ172.6,166.0,165.6,165.4,162.1,160.1,157.9,157.3,153.2,130.04,130.02,129.9,129.8,129.7,128.7,128.6,128.32,128.26,128.1,128.0,127.44,127.41,123.4,114.5,111.0,104.6,101.3,97.3,77.3,77.0,76.7,73.2,71.9,71.7,70.4,70.0,69.2,68.1,62.4。
实施例11
3,7,4'-三-O-己酰基-5-O-(2,3,4,6-四-O-苯甲酰基-β-D-半乳糖)山奈酚糖苷的制备
合成方法如实施例3所示:(c2.4,CHCl3);1HNMR(400MHz,CDCl3)δ8.13(d,J=7.3Hz,2H),8.01-7.97(m,4H),7.85(d,J=7.3Hz,2H),7.79(d,J=8.8Hz,2H),7.83-7.25(m,12H),7.20(d,J=8.8Hz,2H),7.12(d,J=2.1Hz,1H),7.03(d,J=2.0Hz,1H),6.27(dd,J=7.9,10.3Hz,1H),6.08(d,J=3.1Hz,1H),5.71(dd,J=3.4,10.4Hz,1H),5.56(d,J=7.9Hz,1H),4.68(dd,J=6.8,11.1Hz,1H),4.55-4.47(m,2H),2.59(t,J=7.4Hz,2H),2.44-2.37(m,4H),1.8-1.59(m,8H),1.41-1.26(m,12H),0.95-0.88(m,9H);13CNMR(100MHz,CDCl3)δ171.7,171.0,170.4,169.3,166.0,165.6,165.5,157.14,157.06,154.2,153.3,152.7,133.6,133.23,133.19,132.6,130.1,130.0,129.85,129.75,129.4,128.9,128.6,128.4,128.3,128.0,121.8,113.7,109.1,106.6,101.0,77.3,77.0,76.7,71.9,71.6,69.1,68.0,62.2,34.3,34.2,33.7,31.20,31.19,31.1,29.7,24.5,24.3,24.2,22.2,13.9。
以上所述的实施例仅仅是对本发明的优选实施方式进行描述,并非对本发明的范围进行限定,在不脱离本发明设计精神的前提下,本领域普通技术人员对本发明的技术方案作出的各种变形和改进,均应落入本发明权利要求书确定的保护范围内。
Claims (9)
1.一种黄酮类化合物5-O-糖苷的制备方法,其特征在于,包含下列步骤:
将黄酮受体2和糖基炔酯给体3进行糖苷化反应,即可制得黄酮5-O-糖苷化产物1;
其中,R1为本领域常用的羟基保护基,所述的保护基较佳的为苄基(Bn),己酰基,叔丁基二甲基硅基(TBS);
R2为H或者OR’,其中R’为本领域常用的羟基保护基,所述的保护基较佳的为苄基(Bn),己酰基,叔丁基二甲基硅基(TBS);
R3为全保护的β-D-葡萄糖基、全保护的α-D-葡萄糖基、全保护的β-D-半乳糖基、全保护的α-D-半乳糖基、全保护的β-D-甘露糖基、全保护的α-D-甘露糖基、全保护的β-D-木糖基、全保护的α-D-木糖基、全保护的β-D-2-氨基葡萄糖基、全保护的α-D-2-氨基葡萄糖基、全保护的α-L-鼠李糖基、全保护的β-L-鼠李糖基、全保护的α-D-核糖基、全保护的β-D-核糖基、全保护的α-L-核糖基、全保护的β-L-核糖基、全保护的α-D-阿拉伯糖基、全保护的β-D-阿拉伯糖基、全保护的α-L-阿拉伯糖基、全保护的β-L-阿拉伯糖基、全保护的α-L-岩藻糖基、全保护的β-L-岩藻糖基、全保护的β-D-葡萄糖醛酸基、全保护的α-D-葡萄糖醛酸基、全保护的β-D-半乳糖醛酸基、或者全保护的α-D-半乳糖醛酸基;其中糖上的保护基为乙酰基、苯甲酰基或苄基;
R4表示未取代、单取代、二取代、三取代或四取代,R4为H、甲氧基、乙氧基、甲硫基、乙硫基、二甲氨基、二乙氨基、N3、CN、NO2基、三氟甲基和三氯甲基中的一种或多种;
R5为H、甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、环丙基、环丁基、环戊基、环己基、苯基、对甲氧基苯基、对硝基苯基、邻甲氧基苯基或邻硝基苯基。
2.根据权利要求1所述的一种黄酮类化合物5-O-糖苷的制备方法,其特征在于,所述的制备黄酮5-位氧苷1的糖苷化反应包含下列步骤:有机溶剂中,在干燥剂存在下,在惰性气体保护下,在亲炔基路易斯酸的作用下,将黄酮受体2和糖基炔酯给体3进行糖苷化反应,即可。
3.根据权利要求2所述的一种黄酮类化合物5-O-糖苷的制备方法,其特征在于,所述的制备黄酮5-位氧苷化合物1的反应中的有机溶剂为干燥的二氯甲烷、甲苯、硝基甲烷和乙腈中的一种或多种。
4.根据权利要求2所述的一种黄酮类化合物5-O-糖苷的制备方法,其特征在于,所述的制备黄酮5-位氧苷1的反应中的亲炔基路易斯酸为AuCl、AuCl3、AuLOTf、AuLNTf、HgOTf和PtCl2中的一种或多种,其中,L为本领域常规的膦配体三丁基膦、三乙基膦、三苯基膦或三金刚烷基膦中的一种或多种。
5.根据权利要求2所述的一种黄酮类化合物5-O-糖苷的制备方法,其特征在于,所述的制备黄酮5-位氧苷1的糖苷化反应中,所述的亲炔基路易斯酸的用量为糖基炔酯给体3的摩尔量的0.001~1倍,最佳为0.2倍。
6.根据权利要求2所述的一种黄酮类化合物5-O-糖苷的制备方法,其特征在于,所述的制备黄酮5-位氧苷1的糖苷化反应的温度为0~80℃,最佳为30℃;所述的制备黄酮5-位氧苷1的糖苷化反应的时间为2~6小时。
7.根据权利要求2所述的一种黄酮类化合物5-O-糖苷的制备方法,其特征在于,所述的制备黄酮5-位氧苷化合物1的糖苷化反应在干燥剂的存在下进行,干燥剂的用量为糖基炔酯给体3的摩尔量的1.0~4.0倍。
8.根据权利要求7所述的一种黄酮类化合物5-O-糖苷的制备方法,其特征在于,所述的干燥剂为分子筛、分子筛、分子筛、酸洗的分子筛、酸洗的分子筛、酸洗的分子筛、无水硫酸钠、无水硫酸钙、无水硫酸铜和无水硫酸镁中的一种或多种;干燥剂的用量为糖基炔酯给体3的摩尔量为2.0倍。
9.根据权利要求2所述的一种黄酮类化合物5-O-糖苷的制备方法,其特征在于,所述的糖基炔酯给体3由下列方法制得:将异头位裸露的糖基R3OH和炔酸4进行酯化反应,即可;
其中,各基团的定义均同权利要求1或2所述。
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CN106632518A (zh) * | 2017-01-17 | 2017-05-10 | 江西师范大学 | 一种鬼臼毒素4‑oh衍生物的制备方法 |
WO2021179530A1 (zh) * | 2020-03-12 | 2021-09-16 | 中国科学院植物研究所 | 一种黄酮苷类物质及其糖基转移酶基因在调控植物对杂草抗性中的应用 |
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