CN109265486A - A kind of compound and its preparation method and application of the element of base containing ferrocene - Google Patents
A kind of compound and its preparation method and application of the element of base containing ferrocene Download PDFInfo
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- CN109265486A CN109265486A CN201811239145.1A CN201811239145A CN109265486A CN 109265486 A CN109265486 A CN 109265486A CN 201811239145 A CN201811239145 A CN 201811239145A CN 109265486 A CN109265486 A CN 109265486A
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- Prior art keywords
- unsubstituted
- substituted
- compound
- ferrocene
- alkyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 68
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 title claims abstract description 63
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 108020004414 DNA Proteins 0.000 claims description 38
- 125000001118 alkylidene group Chemical group 0.000 claims description 19
- 238000006467 substitution reaction Methods 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- -1 ferrocene Compound Chemical class 0.000 claims description 16
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 238000009396 hybridization Methods 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 238000004458 analytical method Methods 0.000 claims description 11
- 230000005518 electrochemistry Effects 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 108020004635 Complementary DNA Proteins 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 238000010804 cDNA synthesis Methods 0.000 claims description 9
- 239000002299 complementary DNA Substances 0.000 claims description 9
- 238000004365 square wave voltammetry Methods 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims description 2
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims description 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 2
- 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 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 150000001805 chlorine compounds Chemical class 0.000 claims description 2
- AXKUXUCZSNIGCK-UHFFFAOYSA-N chlorooxyphosphonamidous acid Chemical compound NP(O)OCl AXKUXUCZSNIGCK-UHFFFAOYSA-N 0.000 claims description 2
- 238000005516 engineering process Methods 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 238000007689 inspection Methods 0.000 claims 1
- 230000017260 vegetative to reproductive phase transition of meristem Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 60
- 239000002585 base Substances 0.000 description 56
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 38
- 239000000243 solution Substances 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 150000007523 nucleic acids Chemical class 0.000 description 15
- 108020004707 nucleic acids Proteins 0.000 description 12
- 102000039446 nucleic acids Human genes 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 7
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- JBWYRBLDOOOJEU-UHFFFAOYSA-N 1-[chloro-(4-methoxyphenyl)-phenylmethyl]-4-methoxybenzene Chemical compound C1=CC(OC)=CC=C1C(Cl)(C=1C=CC(OC)=CC=1)C1=CC=CC=C1 JBWYRBLDOOOJEU-UHFFFAOYSA-N 0.000 description 4
- 238000004679 31P NMR spectroscopy Methods 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- UIBHKZCMOPHOOT-UHFFFAOYSA-N NP(N)(=O)NCl Chemical compound NP(N)(=O)NCl UIBHKZCMOPHOOT-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 238000005292 vacuum distillation Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Substances CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 description 1
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- BMKQKXUVJOGVJC-UHFFFAOYSA-N C(C)(C)OC(C(C)C)OOCCCC Chemical compound C(C)(C)OC(C(C)C)OOCCCC BMKQKXUVJOGVJC-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 235000004237 Crocus Nutrition 0.000 description 1
- 241000596148 Crocus Species 0.000 description 1
- 229910017112 Fe—C Inorganic materials 0.000 description 1
- 229910017108 Fe—Fe Inorganic materials 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000007990 PIPES buffer Substances 0.000 description 1
- 101500027983 Rattus norvegicus Octadecaneuropeptide Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 241001625808 Trona Species 0.000 description 1
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- FUSJZTVOKYJFPI-UHFFFAOYSA-N cyclopentane;iron;5-methylcyclopenta-1,3-diene Chemical compound [Fe].[CH-]1[CH-][CH-][CH-][CH-]1.C[C-]1C=CC=C1 FUSJZTVOKYJFPI-UHFFFAOYSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000840 electrochemical analysis Methods 0.000 description 1
- 238000000835 electrochemical detection Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- COCAUCFPFHUGAA-MGNBDDOMSA-N n-[3-[(1s,7s)-5-amino-4-thia-6-azabicyclo[5.1.0]oct-5-en-7-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound C=1C=C(F)C([C@@]23N=C(SCC[C@@H]2C3)N)=CC=1NC(=O)C1=CC=C(Cl)C=N1 COCAUCFPFHUGAA-MGNBDDOMSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 125000004354 sulfur functional group Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- RJFSDTDWWBECIL-UHFFFAOYSA-N trifluoro(methyl)-$l^{4}-sulfane Chemical compound CS(F)(F)F RJFSDTDWWBECIL-UHFFFAOYSA-N 0.000 description 1
- 238000004832 voltammetry Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic Table
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/48—Systems using polarography, i.e. measuring changes in current under a slowly-varying voltage
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
Abstract
The invention discloses a kind of compound and its preparation method and application of element of base containing ferrocene, the structural formula of the compound of the element of base containing ferrocene is shown in formula I:
Description
Technical field
The present invention relates to biomedicine fields, compound and its preparation more particularly to a kind of element of base containing ferrocene
Methods and applications.
Background technique
Nucleic acid molecules are the carriers of hereditary information, and the hereditary information of nearly all life is stored within nucleic acid molecules on the earth
In.Since the ability of traditional natural base element (A/T/C/G/U) carrying encoded information is limited, more and more artificial base members
Element is developed, and imparts the function of nucleic acid molecules multiplicity, and in biology, medicine, nanotechnology and life science
Field has important researching value.
In recent years, ferrocene moleculeBecause its brilliant redox characteristic has been widely used in electrochemistry
In the research of sensor and functional nucleic acid nano material.In addition, researcher by a variety of chemical crosslinking modes successfully
Ferrocene molecule and nucleic acid molecules are combined together electrochemical sensor (the Barton J K constructed based on nucleic acid molecules
et al.Nature biotechnology,2003,21(10):1192-1199；Huazhong Y et al.Chemical
Society Reviews,2014,43(2):518-529.)。
However, the side of report being connected to ferrocene molecule by way of flexible alkyl chains or C-C key connection on DNA
Method is difficult to realize accurately detect the electric charge transfer interaction between DNA base.It is found by investigation, due to adjacent in b form dna
The distance between base is similar to ferrocene molecule Cp ring pore size, and ferrocene molecule can be used as nucleic acid backbone component.Cause
This, the present invention reports the compound for synthesizing a kind of element of base containing ferroceneAnd its system
Preparation Method, and ferrocene molecule is mixed by each base position of DNA by DNA solid phase synthesis technique and hybridizes thing to monitor nucleic acid
Part realizes the variation for quickly and accurately detecting mononucleotide level on an atomic scale.
Summary of the invention
It is described to contain the present invention is directed to overcome the deficiencies of the prior art and provide a kind of compound of element of base containing ferrocene
The structural formula of the compound of ferrocene base element is shown in formula I:
Wherein, Z is selected from nothing, substituted or unsubstituted ribosyl, substituted or unsubstituted deoxyribosyl, other than ring type
Nothing, substituted or unsubstituted chiral or achirality propylene glycol structure；The substitution refers to be replaced by group chosen from the followings :-O-P
(NRdRe)-O- (substituted or unsubstituted C1-C6 alkylidene)-CN ,-(C1-C6 alkylidene)-O-C (RfRgRh)；Wherein, in-O-P
(NRdRe) R in-O- (substituted or unsubstituted C1-C6 alkylidene)-CNdAnd ReIt may be the same or different, RdAnd ReSeparately select
From C1-C6 alkyl, C1-C6 alkoxy；The substitution described in the substituted or unsubstituted C1-C6 alkylidene refers to by following base
Group replaces: C1-C6 alkyl, C1-C6 alkoxy, halogen；In-(C1-C6 alkylidene)-O-C (RfRgRh) in Rf、Rg、RhIt can be identical
Or different, Rf、Rg、RhIt is separately selected from substituted or unsubstituted phenyl, described in the substituted or unsubstituted phenyl
Substitution refer to and replaced by substituent group chosen from the followings: C1-C6 alkyl, C1-C6 alkoxy；
L is the unit for connecting ferrocene and Z structure, including alkyl chain, PEG, OEG, the structure containing carbonyl (- C=O), is contained
N, the heteroatomic C1-C6 alkyl such as S, O；
R is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted
It is C3-C6 naphthenic base, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, substituted or unsubstituted
Heteroatomic C1-C6 Heterocyclylalkyl ,-(C=O) phenyl of N, O, S are selected from containing 1-3, it is substituted or unsubstituted to be selected from containing 1-3
N, the heteroatomic C1-C6 Heterocyclylalkyl of O, S；Substituted or unsubstituted heteroatomic aromatic rings or heterocycle containing N, O, S,
In, the substitution, which refers to, to be optionally substituted by halogen.
Preferably, in the compound, Z is had the following structure :-R1-O-P(NRdRe)-O- (substituted or unsubstituted C1-
C6 alkylidene)-CN, wherein R1Selected from the substituted or unsubstituted heteroatomic C1-C6 heterocycle alkane for being selected from N, O, S containing 1-3
Base, substituted or unsubstituted C3-C6 naphthenic base, substituted or unsubstituted C1-C6 alkylidene, substituted or unsubstituted C2-C12 are sub-
Alkenyl, substituted or unsubstituted C2-C12 alkynylene, substituted or unsubstituted C6-C10 aryl, it is substituted or unsubstituted contain 1-3
A heteroatomic C5-C10 heteroaryl selected from N, O, S；The substitution refers to selected from the substitution of following substituent group :-(C1-C6 alkylene
Base)-O-C (RfRgRh), wherein Rf、Rg、RhIt may be the same or different, Rf、Rg、RhSeparately it is selected from substituted or unsubstituted benzene
Base, substitution refers to described in substituted or unsubstituted phenyl is replaced by substituent group chosen from the followings: C1-C6 alkyl, C1-C6 alcoxyl
Base；RdAnd ReIt may be the same or different, RdAnd ReSeparately selected from substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted
C1-C6 alkoxy；Substitution refers to described in the substituted or unsubstituted C1-C6 alkylidene is replaced by following group: C1-C6
Alkyl, C1-C6 alkoxy, halogen.
Preferably, the R1For the substituted C3-C6 Heterocyclylalkyl containing 1 hetero atom O, the substitution refers to by following group
Replace :-(C1-C6 alkylidene)-O- (4,4'- dual-methoxy trityl)；And/or RdAnd ReIt is identical, and be isopropyl.
Preferably, the RaAnd RbIt may be the same or different, RaAnd RbSeparately be selected from the group: H ,-(C=O) phenyl,
C1-C3 alkyl, C1-C3 halogenated alkyl.
Preferably, the compound is selected from compound S2, S3, S4, S8, S9, S10, S12, S13, S14, S18, S19,
S20:
The preparation method technology path of the compound of the above-mentioned element of base containing ferrocene is as follows:
The method comprises the concrete steps that:
(1) by ferrocene analog derivativeWithReaction, obtains the compound of the element of base containing ferrocene；
(2) by step (1) products therefrom and 4, the reaction of 4 '-dimethoxytrityl chlorides obtains the member of base containing ferrocene
The compound of element；
(3) step (2) products therefrom is reacted with chloro phosphoramidite, obtains the compound of the element of base containing ferrocene.
The compound of the element of base containing ferrocene can be used for preparing that the DNA containing the compound is single-stranded or double-stranded, RNA is mono-
Chain or double-stranded material and combinations thereof substance.When the DNA and different complementary DNA hybridization act on, it is double monitoring can be passed through
Chain melts the variation of the mutation analysis mononucleotide level of chain temperature.
The compound of the element of base containing ferrocene can be used for preparing differentiation traditional natural base (A/T/C/G) in DNA
Detect preparation.It is the charge mobility for detecting the DNA by electrochemistry square wave voltammetry and being acted on from different complementary DNA hybridizations
Variation realize that the variation of quickly analysis mononucleotide level passes through when the DNA is from different complementary DNA hybridization effect
Change in location of the electrochemistry square wave voltammetry detection discovery ferrocene molecule in DNA determines the variation of charge mobility, real
The now quickly variation of analysis mononucleotide level.
The compound of the element of base containing ferrocene can be used for preparing macromolecular material.The macromolecular material is selected from
(but being not limited to) nucleic acid, polypeptide, polymer.
The present inventor does not have found report of the ferrocene as hydrophobic bases by investigation extensively.Therefore by depth grinding
Study carefully, has developed the compound of the serial base element containing ferrocene, complete the present invention.This hair is for the first time using ferrocene as alkali
Base element is introduced into any base position in DNA/RNA, by electrochemistry square wave voltammetry detect the DNA from it is different mutual
The variation of quickly analysis mononucleotide level is realized in the variation for mending the charge mobility of DNA hybridization effect.In addition, additionally providing one
Kind macromolecular material, the macromolecular material is comprising compound described in first aspect present invention or as described in first aspect present invention
Compound is built-up.
Compared with prior art, the present invention has following major advantage:
(1) compound structure is optimal, is work perfectly well as monomer synthesis in any base position in DNA/RNA.
(2) compound has redox characteristic, can be used for the variation of Electrochemical Detection analysis mononucleotide level.
Detailed description of the invention
Fig. 1 is that the DNA passes through electrochemistry square wave voltammetry detection variation diagram；
Fig. 2 is detected and is realized by electrochemistry square wave voltammetry when the DNA is acted on from different complementary DNA hybridizations
The quickly variation diagram of analysis mononucleotide level.
Specific embodiment
" halogen " refers to F, Cl, Br and I." C1-C6 alkyl " refers to the alkyl of the linear chain or branched chain including 1-6 carbon atom,
Such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl group, tert-butyl or similar group." C1-C6 alkoxy " includes 1-6
The alkoxy of the linear chain or branched chain of a carbon atom.Such as methoxyl group, ethyoxyl, propoxyl group, isopropoxy, butoxy, isobutyl oxygen
Base, tert-butoxy or similar group." alkyl " includes saturation or unsaturation, straight chain, branch, cricoid 1-10 carbon atom
Full carbon alkyl or in which the alkyl that is replaced by hetero atoms such as oxygen, nitrogen, sulphur of 1-3 carbon atom, and by 1 or 1 or more
The aralkyl of carbon atom connection.In addition, the alkyl is unsubstituted or substituted." aryl " includes condensed or non-condensed
Aryl, usually contains 6-30 carbon atom, and representative aryl includes the heteroatomic fragrance such as phenyl, naphthalene or oxygen-containing, nitrogen, sulphur
Group." DMTr " refers to 4,4'- dual-methoxy trityl.
In the following examples, the experimental methods for specific conditions are not specified, usually according to normal condition such as Sambrook et al.,
Molecular cloning: described in laboratory manual (New York:Cold SpringHarbor Laboratory Press, 1989)
Condition, or according to the normal condition proposed by manufacturer.Unless otherwise stated, otherwise percentage and number are calculated by weight.
The synthesis of 1 compound S4 of embodiment
Compound carboxyl ferrocene S1 (1g, 4.34mmol) is dissolved in anhydrous DMF, by n,N-diisopropylethylamine-DIPEA
After (0.84g, 6.51mmol) and benzotriazole -1- tetramethyl hexafluorophosphoric acid ester-HBTU (1.64g, 4.34mmol) activation, with
After S-3- amino -1,2-PD (0.39g, 4.34mmol) condensation is reacted at room temperature 3 hours, rotation removes solvent, silica gel column chromatography
(methylene chloride: methanol=95:5, Rf=0.3) purifying obtains Chinese red compound S2 (yield: 95%)
1H NMR (400MHz, DMSO-d6): 7.84 (t, J=5.2Hz, 1H), 4.93-4.8 (m, 3H), 4.65 (s, 1H),
4.33(s,2H),4.18(s,5H),3.64(m,1H),3.42-3.18(m,4H)；
13C NMR (100MHz, DMSO-d6): 170.27 (C=O), 76.94 (ipso Cp), 71.27,70.42,69.85,
68.70,64.31,53.89,42.89.MS(ESI-)m/z 303[M+e-]+.
4,4 '-bi-methoxy trityl group chlorine are added in the anhydrous pyridine solution of compound S2 (1g, 3.30mmol)
The dichloromethane solution of (DMTrCl, 1.34g, 3.96mmol) is restored to and reacted at room temperature after stirring 30 minutes under condition of ice bath
Night.Vacuum distillation removes pyridine, crude product column chromatography for separation (ethyl acetate: petroleum ether: triethylamine=35:65:1, Rf=0.5)
Obtain compound S3 (yield: 60%).
1H NMR(CD3CN, 400MHz): 7.47 (d, 2H, J=8Hz), 7.38-7.26 (m, 6H), 7.23-7.17 (m,
1H), 6.85 (d, 4H, J=8Hz), 6.72 (t, 1H), 4.63 (s, 2H), 4.31 (s, 2H), 4.13 (s, 1H) 4.08 (s, 5H),
3.88(m,1H)3.73(s,6H),3.48(m,1H),3.33(m,1H),3.07(m,2H)；
13C NMR (DMSO-d6,100MHz): 169.92 (C=O), 158.49 (ipso dmt), 145.68 (ipso Ar),
136.36(ipso Ar),136.31(ipso Ar),130.28(CH-Ar),130.25(CH-Ar),128.27(CH-Ar),
128.23(CH-Ar),127.03(CH-Ar),113.60(CH-Ar),85.68(ipso-cp),77.07,70.29,69.79,
69.48,68.66,66.52,55.49,45.94,43.56.MS(ESI)m/z 628.2[M+Na]+.
Compound S3 (1g, 1.65mmol) is dissolved in anhydrous methylene chloride (15mL), under condition of ice bath, is sequentially added into two
Diisopropylethylamine (0.43g, 3.30mmol), chloro phosphoramide (0.47g, 1.98mmol).After addition, reaction solution liter
To room temperature, the reaction was continued 1 hour, and 20mL methylene chloride is then added.Solution is respectively with saturation NaHCO3Solution and salt are washed simultaneously
Dry with anhydrous sodium sulfate, rotation is except after solvent, crude product column chromatographs (ethyl acetate: petroleum ether: triethylamine=20:80:1, Rf=
0.5) yellow solid compound S4 (isomers, yield: 75%) are obtained.
1H NMR (400MHz, CDCl3): 7.49 (d, 2H, J=7.6Hz), 7.37-7.35 (d, 4H, J=8.4Hz),
7.31-7.18 (m, 3H), 6.84-6.79 (m, 4H), 6.23 (t, 0.59H, J=5.2Hz), 6.03 (t, 0.31H, J=
5.2Hz),4.61(s,0.63H),4.53(s,1.23H),4.28(s,2H),4.11-4.11(s,5.57H),3.89-3.81(m,
1.38H), 3.74-3.48 (m, 10.74H), 3.32-3.26 (m, 2H), 2.6 (t, 1.25H, J=6.2Hz), 2.45 (t,
0.67H, J=6.2Hz), 2.1 (s, 1H), 1.29-1.12 (m, 12H)；
13C NMR(100MHz,CDCl3):170.09,158.51,144.74,135.86,130.10,128.01,
127.48,126.40,117.69,113.17,86.24,72.51,72.36,70.29,70.13,69.66,68.50,68.27,
67.87,67.55,64.88,64.57,60.35,58.45,58.28,58.10,55.18,24.68,21.02,20.40,
20.25,14.19.MS(ESI)m/z 828.30[M+Na]+.
31P NMR(202MHz,CDCl3)δ149.40(s).
The synthesis of 2 compound S10 of embodiment
Chloro- 3, the 5- bis- of compound methylol ferrocene S5 (1g, 4.63mmol), 1- is de- to chlorobenzoyl oxygroup -2-
Oxygen-D-ribose S6 (1.79g, 4.17mmol), anhydrous Cs2CO3(2.60g, 7.87mmol) is dissolved in anhydrous methylene chloride, and room temperature is stirred
Mix overnight, rotation remove solvent, silica gel column chromatography (methylene chloride: methanol=95:5) purifying obtain Chinese red compound S7 (yield:
80%)
1H NMR(400MHz,CDCl3) δ 7.99-7.91 (m, 4H), 7.43-7.37 (m, 4H), 5.55 (t, J=7.0Hz,
1H), 5.17 (q, J=7.0Hz, 1H), 4.92 (q, J=7.0Hz, 1H), 4.57 (s, 1H), 4.53-4.43 (m, 2H), 4.24
(dd, J=12.3,7.0Hz, 1H), 2.52 (dt, J=12.4,7.0Hz, 1H), 2.27 (dt, J=12.4,7.0Hz, 1H)；
13C NMR(100MHz,CDCl3)δ166.48,166.04,139.87,131.29,130.59,129.17,
129.15,126.84,103.66,81.30,75.20,65.42,64.70,38.95.
Under the conditions of ice bath inert gas shielding, 1M sodium methoxide is added dropwise in the methanol solution of compound S7 (1g, 1.64mmol)
Methanol solution, reaction solution, which is warming up to, to be stirred overnight at room temperature, and rotation removes solvent, silica gel column chromatography (methylene chloride: methanol=95:5)
Purifying obtains Chinese red compound S8 (yield: 95%)
1H NMR(400MHz,CDCl3) δ 5.55 (t, J=7.0Hz, 1H), 4.57 (s, 1H), 4.45 (s, 1H), 3.99 (q,
J=7.0Hz, 1H), 3.85 (qd, J=7.0,5.0Hz, 1H), 3.77 (ddd, J=12.4,7.0,5.5Hz, 1H), 3.52
(ddd, J=12.5,7.0,5.5Hz, 1H), 2.25 (dt, J=12.4,7.0Hz, 1H), 2.00 (dt, J=12.4,7.0Hz,
1H), 1.56 (d, J=5.0Hz, 1H), 1.40 (t, J=5.5Hz, 1H)；
13C NMR(100MHz,CDCl3)δ103.28,87.05,72.54,65.42,63.56,41.95.
4,4 '-bi-methoxy trityl group chlorine are added in the anhydrous pyridine solution of compound S8 (1g, 3.01mmol)
The dichloromethane solution of (DMTrCl, 1.34g, 3.96mmol) is restored to and reacted at room temperature after stirring 30 minutes under condition of ice bath
Night.Vacuum distillation removes pyridine, crude product column chromatography for separation (ethyl acetate: petroleum ether: triethylamine=35:65:1, Rf=0.5)
Obtain compound S9 (yield: 60%).
1H NMR(400MHz,CDCl3)δ7.49–7.43(m,1H),7.35–7.25(m,4H),6.88–6.82(m,2H),
5.55 (t, J=7.0Hz, 1H), 4.57 (s, 0H), 4.45 (s, 0H), 4.19 (q, J=7.0Hz, 1H), 3.85 (qd, J=7.0,
5.0Hz, 1H), 3.80 (s, 3H), 3.60 (dd, J=12.5,7.0Hz, 1H), 3.35 (dd, J=12.4,7.0Hz, 1H), 2.25
(dt, J=12.4,7.0Hz, 1H), 2.00 (dt, J=12.4,7.0Hz, 1H), 1.56 (d, J=5.0Hz, 1H)
13C NMR(100MHz,CDCl3)δ158.66,142.93,135.37,135.35,127.60,113.38,
103.28,87.00,84.92,71.76,65.42,63.83,55.35,41.95.
Compound S9 (0.6g, 0.95mmol) is dissolved in anhydrous methylene chloride (15mL), under condition of ice bath, is sequentially added into
Diisopropyl ethyl amine (0.43g, 3.30mmol), chloro phosphoramide (1.35g, 5.7mmol).After addition, reaction solution
Being raised to room temperature, the reaction was continued 1 hour, and 20mL methylene chloride is then added.Solution is respectively with saturation NaHCO3Solution and salt are washed
And it is dry with anhydrous sodium sulfate, rotation is except after solvent, crude product column chromatographs (ethyl acetate: petroleum ether: triethylamine=20:80:1, Rf
=0.5) yellow solid compound S10 (isomers, yield: 75%) are obtained.
1H NMR(400MHz,CDCl3) δ 7.50-7.42 (m, 3H), 7.35-7.25 (m, 4H), 5.55 (t, J=7.0Hz,
0H), 4.19 (q, J=7.0Hz, 0H), 3.95-3.80 (m, 2H), 3.60 (dd, J=12.4,7.0Hz, 0H), 3.35 (dd, J=
12.4,7.0Hz, 0H), 2.83 (p, J=6.8Hz, 1H), 2.60 (td, J=7.1,1.0Hz, 1H), 2.25 (dt, J=12.4,
7.0Hz, 0H), 2.00 (dt, J=12.4,7.0Hz, 0H), 1.09 (dd, J=25.0,6.8Hz, 6H)
13C NMR(100MHz,CDCl3)δ158.96,144.10,135.49,129.38,128.45,128.32,
128.06,118.60,118.55,113.50,103.73,87.42,81.74,81.70,76.00,75.92,65.12,59.09,
59.02,56.08,44.63,44.53,39.38,39.33,22.96,22.91.
31P NMR(202MHz,CDCl3)δ149.40(s).
The synthesis of 3 compound S14 of embodiment
Be added dropwise under paratoluensulfonyl chloride (6.18g, 31.748mmol) condition of ice bath acetone carboxylic glycerol (4.00g,
In anhydrous pyridine (50.0ml) solution 30.236mmol).Reaction mixture, which is warmed to room temperature, to be stirred overnight.Be removed under reduced pressure must,
Ethyl acetate (50ml) dilution, successively uses 1M HCl (2x 150ml), is saturated NaHCO3(100ml) and saturated salt solution
(200ml) washs the drying of anhydrous sodium sulfate, give light yellow oil.Crude product column chromatography (10-30% ethyl acetate/just oneself
Alkane), obtain the acetone carboxylic glycerol 8.54g (yield 98.6%) that colorless oil (R)-methanesulfonic acid replaces.
[α]D 20=-4.75 ° (c1.0, EtOH) (lit. [α]D 20=-4.6 ° (c 13.0, EtOH))
FT-IR(thin film)vmax(cm-1):3073,2987,2937,2891,1598,1495,1455,1368,
1257,1213,1190,1177,1096,1055,979,829,788,665,555.1H NMR(600MHz,CDCl3,25℃)δ
(ppm)1.31(s,3H,CH3-2),1.34(s,3H,CH3), 2.45 (s, 3H, ArCH), 3.76 (dd, J=5.1and 8.8Hz,
1H,CH2), 3.98 (dd, J=6.0and 10.2Hz, 1H, CH2), 4.01 (dd, J=5.6and 10.3Hz, 1H, CH2),4.03
(dd, J=6.2and 8.8Hz 1H, CH2),4.28(m,1H,CH),7.35(m,2H,arom H),7.79(m,2H,arom
H).
13C NMR(100MHz,CDCl3)δ(ppm):21.54(Ar-CH3),25.05(CH3),26.53(CH3),66.05
(C),69.44(C),72.82(C),109.93(C),127.88(2C,arom C),129.83(2C,arom C),132.55
(arom C),144.99(arom C).HRMS(ESI):calcd.for C13H18O5NaS[M+Na]+309.07672；found
309.0762.Chiral HPLC:Chiralpak 1A,5pm,250x 4.6mm column,hexanes/2-propanol/
Methanol 97:2:1 (v/v/v), 1.0ml/min, Rt=24.20 (99.94%)
(R) the acetone carboxylic glycerol (2.03g, 7.1mmol) that-methanesulfonic acid replaces is dissolved in dimethyl acid imide (3mL), and 3mL is folded
Sodium nitride (1.27g, 19.5mmol) aqueous solution is added dropwise to above-mentioned solution.80 DEG C are heated overnight.It is down to 0 DEG C after reaction, adds
Enter saturated sodium carbonate (50mL).Ether (2 × 50mL) extraction, is washed (50mL).Anhydrous sodium sulfate, which dries, filters, rotates to obtain yellow
Grease (800mg, 72%) is not required to purifying and is directly used in reaction in next step.
Contain the acetonitrile solution of azido compound (0.234g, 1mmol) and alkynyl ferrocene 1 (0.21g, 1mmol) to 8mL
In, diisopropyl ethyl amine (0.323g, 2.5mmol) and cuprous iodide (0.019g, 0.1mmol) is added.Reaction mixture room
Temperature lower stirring 7 hours.Ethyl acetate (30mL) extraction, saturated salt solution (15ml) washing, is filtered, revolving, crude product column chromatography
Obtain 355mg crocus solid S11 (yield: 88%).Rf(40% ethyl acetate: hexane, 0.3)；
1H NMR (400MHz, CDCl3)δ7.59(s,1H,HTriazole),4.76(s,1H,CH2O),4.69(s,1H,
CH2O),4.59–4.42(m,3H,CHO,HCp),4.29(s,2H,HCp),4.15–4.08(m,6H,CH2N,HCp 0),3.76(dd,
J11/49Hz,J21/45.7Hz,1H,CH2N),1.41(s,3H,Me),1.36(s,3H,Me)；
13C NMR(100MHz,CDCl3)δ120.2,110.1,75.6,74.1,69.5,68.6,66.7,66.5,66.4,
51.9,26.7,25.2.
Above compound S11 is hydrolyzed 1 hour in the aqueous solution of acetic acid and is obtained corresponding ferrocene propylene glycol compound
S12 (yield: 99%).Rf(75% ethyl acetate: n-hexane, 0.25)；
1H NMR (300MHz, CDCl3)δ7.56(s,1H,HTriazole),4.70–4.47(m,3H,CH2N,HCp),4.39–
4.30(m,3H,CH2N,HCp),4.19–4.00(m,6H,CHOH,HCp 0),3.73–3.61(m,2H,CH2OH)；
13C NMR(75MHz,CDCl3)δ146.6,120.7,75.2,70.5,69.7,68.9,66.8,63.7,52.8；IR
(Neat):3358,2924,2854,1589,1105,1045,810cm；
HRMS m/z:Calcd for C15H17FeN3O2(M+Na+):350.0568,found:350.0569；[α]D 20=
14.0(c 0.5,MeOH).
4,4 '-bi-methoxy trityl group chlorine are added in the anhydrous pyridine solution of compound S12 (1g, 3.01mmol)
The dichloromethane solution of (DMTrCl, 1.34g, 3.96mmol) is restored to and reacted at room temperature after stirring 30 minutes under condition of ice bath
Night.Vacuum distillation removes pyridine, crude product column chromatography for separation (ethyl acetate: petroleum ether: triethylamine=35:65:1, Rf=0.5)
Obtain compound S13 (yield: 60%).
1H NMR(400MHz,CDCl3)δ8.66(s,1H),7.50–7.42(m,2H),7.35–7.25(m,7H),6.88–
6.82 (m, 4H), 3.98 (dd, J=12.0,6.7Hz, 1H), 3.80 (pd, J=6.8,4.9Hz, 1H), 3.80 (s, 6H), 3.73
(dd, J=12.1,6.9Hz, 1H), 3.62 (dd, J=12.3,6.9Hz, 1H), 3.38 (dd, J=12.4,6.9Hz, 1H),
2.57 (d, J=4.9Hz, 1H)
13C NMR(100MHz,CDCl3)δ167.89,158.66,146.02,143.77,135.37,127.60,
113.38,85.98,68.27,64.61,64.42,55.35,51.89,50.92.
Compound S13 (0.6g, 0.95mmol) is dissolved in anhydrous methylene chloride (15mL), under condition of ice bath, is successively added respectively
Enter diisopropyl ethyl amine (0.43g, 3.30mmol), chloro phosphoramide (1.35g, 5.7mmol).After addition, reaction
Liquid is raised to room temperature, and the reaction was continued 1 hour, and 20mL methylene chloride is then added.Solution is respectively with saturation NaHCO3Solution and saline solution
It washes and dry with anhydrous sodium sulfate, after rotation removes solvent, crude product column chromatography (ethyl acetate: petroleum ether: triethylamine=20:80:1,
Rf=0.5) yellow solid compound S14 (isomers, yield: 75%) are obtained.
1H NMR(400MHz,CDCl3)δ7.50–7.42(m,2H),7.35–7.22(m,7H),6.88–6.82(m,4H),
4.02-3.85 (m, 3H), 3.80 (s, 6H), 3.86-3.69 (m, 2H), 3.62 (dd, J=12.4,6.9Hz, 1H), 3.38 (dd,
J=12.4,6.9Hz, 1H), 2.83 (hept, J=6.8Hz, 2H), 2.60 (td, J=7.0,1.0Hz, 2H), 1.09 (dd, J=
25.0,6.8Hz,12H).
13C NMR(100MHz,CDCl3)δ167.89,158.66,146.02,143.77,135.45,135.41,
135.37,127.60,113.39,85.98,64.42,55.35,50.92.
31P NMR(202MHz,CDCl3)δ149.40(s).
The synthesis of 4 compound S20 of embodiment
Trifluoro methylsulphur is separately added into methylene chloride (1mL) solution of compounds methyl ferrocene methanol (0.5mmol)
Sour aluminium (2.4mg, 5 μm of ol) and diethylene glycol (DEG), above-mentioned solution stir 30 minutes at room temperature.Na is added2CO3 (5%, 0.5mL) is quenched,
Methylene chloride extraction.Anhydrous magnesium sulfate dries, filters, concentrated solvent.Column chromatographs (hexamethylene: ethyl acetate=9:1-1:1) and obtains
Light yellow oil [1- [2- (2- hydroxyl-oxethyl) ethyoxyl] ethyl] ferrocene S16 (1g, 4.63mmol)
1H NMR(CDCl3, 400MHz) and d 1.57 (d, J=6.5Hz, 3H, CH3),2.51(br s,1H,OH),3.50–
3.65(m,6H,CH2), 3.65-3.75 (m, 2H, CH2), 4.10-4.25 (m, 9H, Fc), 4.37 (q, J=6.5Hz, 1H)；
13C NMR(CDCl3,101MHz)d 20.4,61.9,66.3,67.2,68.2,69.1 70.6,72.5,74.2,
89.3.HRMS m/z calcd for C16H22FeO3:318.0918.Found:318.0922.
Anal.Calcd for C16H22FeO3:C,60.40；H,6.97.Found:C,60.33,H,6.52.
Compound S16 [1- [2- (2- hydroxyl-oxethyl) ethyoxyl] ethyl] ferrocene (1g, 4.63mmol), 1- chloro- 3,
5- bis- is to chlorobenzoyl oxygroup -2-deoxy-D-ribose S6 (1.79g, 4.17mmol), anhydrous Cs2CO3(2.60g,
It 7.87mmol) is dissolved in anhydrous methylene chloride, is stirred overnight at room temperature, revolves and removes solvent, silica gel column chromatography (methylene chloride: methanol=95:
5) purifying obtains Chinese red compound S17 (yield: 80%)
Under the conditions of ice bath inert gas shielding, 1M sodium methoxide is added dropwise in the methanol solution of compound S17 (1g, 1.64mmol)
Methanol solution, reaction solution, which is warming up to, to be stirred overnight at room temperature, rotation remove solvent, silica gel column chromatography (methylene chloride: methanol=95:
5) purifying obtains Chinese red compound S18 (yield: 95%)
1H NMR(400MHz,CDCl3) δ 7.99-7.91 (m, 3H), 7.43-7.37 (m, 3H), 5.55 (t, J=7.0Hz,
1H), 5.17 (q, J=7.0Hz, 1H), 4.92 (q, J=7.0Hz, 1H), 4.68 (q, J=6.9Hz, 1H), 4.49 (dd, J=
12.3,7.0Hz, 1H), 4.24 (dd, J=12.3,7.0Hz, 1H), 3.64-3.44 (m, 6H), 2.52 (dt, J=12.4,
7.0Hz, 1H), 2.27 (dt, J=12.4,7.0Hz, 1H), 1.49 (d, J=6.9Hz, 2H)
13C NMR(100MHz,CDCl3)δ103.48,87.05,75.80,72.54,70.07,67.91,65.91,
63.56,41.95,24.44.
4,4 '-bi-methoxy trityl group chlorine are added in the anhydrous pyridine solution of compound S18 (1g, 3.01mmol)
The dichloromethane solution of (DMTrCl, 1.34g, 3.96mmol) is restored to and reacted at room temperature after stirring 30 minutes under condition of ice bath
Night.Vacuum distillation removes pyridine, crude product column chromatography for separation (ethyl acetate: petroleum ether: triethylamine=35:65:1, Rf=0.5)
Obtain compound S19 (yield: 60%).
1H NMR(400MHz,CDCl3)δ7.49–7.43(m,2H),7.35–7.26(m,7H),6.88–6.82(m,4H),
5.55 (t, J=7.0Hz, 1H), 4.68 (q, J=6.9Hz, 1H), 4.19 (q, J=7.0Hz, 1H), 3.85 (qd, J=7.0,
5.0Hz, 1H), 3.80 (s, 5H), 3.64-3.44 (m, 9H), 3.35 (dd, J=12.4,7.0Hz, 1H), 2.25 (dt, J=
12.4,7.0Hz, 1H), 2.00 (dt, J=12.4,7.0Hz, 1H), 1.56 (d, J=5.0Hz, 1H), 1.49 (d, J=6.9Hz,
3H).
13C NMR(100MHz,CDCl3)δ158.66,142.93,135.37,127.60,113.39,103.48,86.99,
84.92,75.80,71.76,70.07,67.91,65.91,63.83,55.35,41.95,24.44.
Compound S19 (0.6g, 0.95mmol) is dissolved in anhydrous methylene chloride (15mL), under condition of ice bath, is successively added respectively
Enter diisopropyl ethyl amine (0.43g, 3.30mmol), chloro phosphoramide (1.35g, 5.7mmol).After addition, reaction
Liquid is raised to room temperature, and the reaction was continued 1 hour, and 20mL methylene chloride is then added.Solution is respectively with saturation NaHCO3Solution and saline solution
It washes and dry with anhydrous sodium sulfate, after rotation removes solvent, crude product column chromatography (ethyl acetate: petroleum ether: triethylamine=20:80:1,
Rf=0.5) yellow solid compound S20 (isomers, yield: 75%) are obtained.
1H NMR(400MHz,CDCl3)δ7.50–7.42(m,2H),7.35–7.26(m,7H),6.88–6.82(m,4H),
5.55 (t, J=7.0Hz, 1H), 4.68 (q, J=6.9Hz, 1H), 4.19 (q, J=7.0Hz, 1H), 3.95-3.80 (m, 5H),
3.80 (s, 4H), 3.64-3.44 (m, 9H), 2.83 (hept, J=6.8Hz, 2H), 2.60 (td, J=7.0,1.0Hz, 2H),
2.25 (dt, J=12.4,7.0Hz, 1H), 2.00 (dt, J=12.4,7.0Hz, 1H), 1.49 (d, J=6.9Hz, 3H), 1.09
(dd, J=25.0,6.8Hz, 12H)
13C NMR(100MHz,CDCl3)δ158.66,142.93,135.36,127.60,118.02,113.39,
103.67,86.99,70.07,67.91,65.92,63.79,55.35,24.44.
31P NMR(202MHz,CDCl3)δ149.40(s).
The synthesis of the nucleic acid of 5 element of base containing ferrocene of embodiment, characterization
For the property for illustrating ferrocene base element well, reference frame is provided for the use of this kind of new material, it is necessary
Characterization it is critically important.We have designed and synthesized the nucleic acid of the serial element of base containing ferrocene, they may be from different complementations
DNA hybridization acts on forming intermolecular duplex structure, and the DNA and different complementations can be detected by electrochemistry square wave voltammetry
The variation of quickly analysis mononucleotide level is realized in the variation of the charge mobility of DNA hybridization effect.
Device information: the synthesis of nucleic acid is using ABI 394DNA/RNA synthesizer, and the test of fusing point is by equipped with SYBR
The real time PCR instrument (7500, Applied Biosystems) of green probe is completed, and electro-chemical test is by CHI760B electrification
Learn work station (Shanghai Chen Hua Instrument Ltd.) completion.
The sequence of associated nucleic acid is as shown in table 1:
Table 1
| ODNs | Sequence table |
| a1 | 5’-FeGGACTCTCTCAATG-3’(SEQ ID NO.1) |
| a2 | 5’-TGFeACTCTCTCAATG-3’(SEQ ID NO.2) |
| a3 | 5’-TGGACTCFeCTCAATG-3’(SEQ ID NO.3) |
| a4 | 5’-TGGACTCTCTCAFeTG-3’(SEQ ID NO.4) |
| a5 | 5’-CATTGAGFeGAGTCCA-3’(SEQ ID NO.5) |
In table 1, Fe represents the corresponding ferrocene base element obtained from compound synthesis.Because of ferrocene base element
Equally there is redox characteristic, when above-mentioned DNA and different complementary DNA hybridization act on, can be melted by monitoring double-strand
The variation of the mutation analysis mononucleotide level of chain temperature；Or by electrochemistry square wave voltammetry detect above-mentioned DNA from it is different
Complementary DNA hybridization effect charge mobility variation realize quickly analysis mononucleotide level variation.
Above-mentioned nucleic acid is to be synthesized with solid phase synthetic instrument, post-process deprotection, HPLC purification process to get to corresponding core
Acid product.
The thermodynamic stability test result of associated nucleic acid hybridization is as shown in table 2:
Table 2
| Entry | N-N | Tm(℃) |
| 1 | Fe-A | 56.8 |
| 2 | Fe-T | 51 |
| 3 | Fe-G | 50 |
| 4 | Fe-C | 52.7 |
| 5 | Fe-Fe | 52 |
| 6 | A-T | 60.9 |
Condition: 1 μM of DNA, 100mM NaCl, 10mM MgCl2,10mM PIPES, pH 7.0.
Nucleic acid sequence used: 5 '-TGGACTCNCTCAATG-3 ' (SEQ ID NO.6), the meaning of N are shown in Table a left side for 2 the 2nd column
Bian Lie；
3 '-ACCTGAGNGAGTTAC-5 ' (SEQ ID NO.7), the meaning of N are shown in Table the right-hand column of 2 the 2nd column；
The melting temperature of DNA double chain refers to that double-strand separately becomes single-stranded critical-temperature in the solution.Above-mentioned test result
Prove, ferrocene base element of Fe can with trona base element A (entry 1), T (entry 2), G (entry 3), C (entry 4) and
Base-pair is formed with ferrocene base element of Fe itself (entry 5), and forms duplex structure in turn.With natural Base comparison
The conjugate planes of (entry 6), this ferrocene base element of Fe are slightly smaller, therefore judge from fusing point, and this double-strand is unstable and two
The pairing situation of luxuriant iron base element of Fe and various natural bases is not exclusively.
In addition, as can be seen from Figure 2: when the DNA is acted on from different complementary DNA hybridizations, passing through electrochemistry square wave
Change in location of the voltammetry detection discovery ferrocene molecule in DNA determines the variation of charge mobility；Under certain condition,
Different interactions shows the variation of different electrochemical signals between ferrocene base element of Fe and natural base
To realize the variation of quickly analysis mononucleotide level.
SEQUENCE LISTING
<110>Hunan University
<120>a kind of compound and its preparation method and application of the element of base containing ferrocene
<160> 7
<170> PatentIn version 3.3
<210> 1
<211> 14
<212> DNA
<213>artificial synthesized
<220>
<221> misc_feature
<222>(1) ... (1)
<223>5 ' the first bit bases of end are ferrocene modified base
<400> 1
ggactctctc aatg 14
<210> 2
<211> 14
<212> DNA
<213>artificial synthesized
<220>
<221> misc_feature
<222>(2) ... (3)
<223>5 ' end seconds or third bit base are ferrocene modified base
<400> 2
tgactctctc aatg 14
<210> 3
<211> 14
<212> DNA
<213>artificial synthesized
<220>
<221> misc_feature
<222>(7) ... (8)
<223>5 ' the 7th, ends or the 8th bit base are ferrocene modified base
<400> 3
tggactcctc aatg 14
<210> 4
<211> 14
<212> DNA
<213>artificial synthesized
<220>
<221> misc_feature
<222>(12) ... (13)
<223>5 ' the 12nd, ends or the 13rd bit base are ferrocene modified base
<400> 4
tggactctct catg 14
<210> 5
<211> 14
<212> DNA
<213>artificial synthesized
<220>
<221> misc_feature
<222>(7) ... (8)
<223>5 ' the 7th, ends or the 8th bit base are ferrocene modified base
<400> 5
cattgaggag tcca 14
<210> 6
<211> 15
<212> DNA
<213>artificial synthesized
<220>
<221> misc_feature
<222> (8)..(8)
<223>n is a, c, g, t or ferrocene
<400> 6
tggactcnct caatg 15
<210> 7
<211> 15
<212> DNA
<213>artificial synthesized
<220>
<221> misc_feature
<222> (8)..(8)
<223>n is a, c, g, t or ferrocene
<400> 7
acctgagnga gttac 15
Claims (10)
1. a kind of compound of the element of base containing ferrocene, which is characterized in that the compound of the element of base containing ferrocene
Structural formula is shown in formula I:
Wherein, Z is selected from nothing, the nothing of substituted or unsubstituted ribosyl, substituted or unsubstituted deoxyribosyl, other than ring type, takes
Generation or unsubstituted chiral or achirality propylene glycol structure；The substitution refers to be replaced by group chosen from the followings :-O-P (NRdRe)-
O- (substituted or unsubstituted C1-C6 alkylidene)-CN ,-(C1-C6 alkylidene)-O-C (RfRgRh)；Wherein, in-O-P (NRdRe)-
R in O- (substituted or unsubstituted C1-C6 alkylidene)-CNdAnd ReIt may be the same or different, RdAnd ReSeparately it is selected from C1-C6
Alkyl, C1-C6 alkoxy；The substitution described in the substituted or unsubstituted C1-C6 alkylidene refers to be replaced by following group:
C1-C6 alkyl, C1-C6 alkoxy, halogen；In-(C1-C6 alkylidene)-O-C (RfRgRh) in Rf、Rg、RhIt may be the same or different,
Rf、Rg、RhSeparately it is selected from substituted or unsubstituted phenyl, the substitution described in the substituted or unsubstituted phenyl
Finger is replaced by substituent group chosen from the followings: C1-C6 alkyl, C1-C6 alkoxy；
L is the unit for connecting ferrocene and Z structure, including alkyl chain, PEG, OEG, the structure containing carbonyl (- C=O), contains N, S, O
Etc. heteroatomic C1-C6 alkyl；
R is H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-
C6 naphthenic base, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, it is substituted or unsubstituted contain 1-
3 are selected from heteroatomic C1-C6 Heterocyclylalkyl ,-(C=O) phenyl of N, O, S, it is substituted or unsubstituted containing 1-3 selected from N, O,
The heteroatomic C1-C6 Heterocyclylalkyl of S；Substituted or unsubstituted heteroatomic aromatic rings or heterocycle containing N, O, S, wherein institute
It states substitution and refers to and be optionally substituted by halogen.
2. the compound of the element of base containing ferrocene as described in claim 1, which is characterized in that in the compound, Z has
Such as flowering structure :-R1-O-P(NRdRe)-O- (substituted or unsubstituted C1-C6 alkylidene)-CN, wherein R1It does not take selected from substitution or
The heteroatomic C1-C6 Heterocyclylalkyls containing 1-3 selected from N, O, S in generation, substituted or unsubstituted C3-C6 naphthenic base, replace or
Unsubstituted C1-C6 alkylidene, substituted or unsubstituted C2-C12 alkynylene, takes substituted or unsubstituted C2-C12 alkenylene
Generation or unsubstituted C6-C10 aryl, the substituted or unsubstituted heteroatomic C5-C10 heteroaryl that N, O, S are selected from containing 1-3；
The substitution refers to selected from the substitution of following substituent group :-(C1-C6 alkylidene)-O-C (RfRgRh), wherein Rf、Rg、RhCan it is identical or
Difference, Rf、Rg、RhIt is separately selected from substituted or unsubstituted phenyl, replaces described in substituted or unsubstituted phenyl and refers to
Replaced by substituent group chosen from the followings: C1-C6 alkyl, C1-C6 alkoxy；RdAnd ReIt may be the same or different, RdAnd ReIndependently
Ground is selected from substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy；Described substituted or unsubstituted
Substitution refers to described in C1-C6 alkylidene is replaced by following group: C1-C6 alkyl, C1-C6 alkoxy, halogen.
3. the compound of the element of base containing ferrocene as claimed in claim 2, which is characterized in that the R1Contain 1 for substituted
The C3-C6 Heterocyclylalkyl of hetero atom O, the substitution refers to be replaced by following group :-(C1-C6 alkylidene)-O- (4,4'- bis- methoxies
Base trityl)；And/or RdAnd ReIt is identical, and be isopropyl.
4. the compound of the element of base containing ferrocene as described in claim 1, which is characterized in that the RaAnd RbCan it is identical or
Difference, RaAnd RbIt is separately selected from the group: H ,-(C=O) phenyl, C1-C3 alkyl, C1-C3 halogenated alkyl.
5. the compound of the element of base containing ferrocene as described in claim 1, which is characterized in that the compound is selected from chemical combination
Object S2, S3, S4, S8, S9, S10, S12, S13, S14, S18, S19, S20:
6. the preparation method of the compound of the element of base containing ferrocene as described in any one of claim 1 to 5, which is characterized in that
The technology path of the method is as follows:
The method comprises the concrete steps that:
(1) by ferrocene analog derivativeReaction, obtains the compound of the element of base containing ferrocene；
(2) by step (1) products therefrom and 4, the reaction of 4 '-dimethoxytrityl chlorides obtains the element of base containing ferrocene
Compound；
(3) step (2) products therefrom is reacted with chloro phosphoramidite, obtains the compound of the element of base containing ferrocene.
7. the compound of the element of base containing ferrocene is single-stranded or double in DNA of the preparation containing the compound as described in claim 1 to 5
Application in chain, RNA single strand or double-stranded material and combinations thereof substance.
8. the compound of the element of base containing ferrocene distinguishes the inspection of traditional natural base in preparation DNA as described in claim 1 to 5
Survey the application in preparation.
9. application as claimed in claim 8, which is characterized in that the application is by described in the detection of electrochemistry square wave voltammetry
The variation of quickly analysis mononucleotide level is realized in the variation for the charge mobility that DNA is acted on from different complementary DNA hybridizations, when
When the DNA is acted on from different complementary DNA hybridizations, discovery ferrocene molecule is detected in DNA by electrochemistry square wave voltammetry
In change in location determine the variation of charge mobility.
10. the compound of the element of base containing ferrocene is preparing the application in macromolecular material as described in claim 1 to 5.
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| CN111956809A (en) * | 2020-08-21 | 2020-11-20 | 湖南大学 | Nucleic acid biological medicine, preparation method thereof and application thereof in tumor treatment |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1477331A (en) * | 1974-02-05 | 1977-06-22 | Fisons Ltd | Ferrocene derivatives |
| US20030143556A1 (en) * | 2001-04-03 | 2003-07-31 | Gary Blackburn | Nucleic acid reactions using labels with different redox potentials |
-
2018
- 2018-10-23 CN CN201811239145.1A patent/CN109265486A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1477331A (en) * | 1974-02-05 | 1977-06-22 | Fisons Ltd | Ferrocene derivatives |
| US20030143556A1 (en) * | 2001-04-03 | 2003-07-31 | Gary Blackburn | Nucleic acid reactions using labels with different redox potentials |
Non-Patent Citations (5)
| Title |
|---|
| HUY V. NGUYEN ET AL.: "A ferrocene nucleic acid oligomer as an organometallic structural mimic of DNA", 《CHEM. COMMUN.》 * |
| RITA MAZZONI ET AL.: "Iron-Catalyzed Ferrocenylmethanol OH Substitution by S,N,P,and C Nucleophiles", 《EUR. J. INORG. CHEM.》 * |
| SURESH UDHAVRAO SHISODIA ET AL.: "New examples of template catalysis based processes: glycerol-like units as efficient promoters for dehydrative nucleophilic substitutions of ferrocenylmethanol", 《TETRAHEDRON LETTERS》 * |
| V. SAI SUDHIR ET AL.: "Click chemistry inspired synthesis of ferrocene amino acids and other derivatives", 《TETRAHEDRON》 * |
| WALTHER G. JARY ET AL.: "Asymmetric dihydroxylation reactions leading to novel chiral ferrocene derivatives", 《TETRAHEDRON: ASYMMETRY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111956809A (en) * | 2020-08-21 | 2020-11-20 | 湖南大学 | Nucleic acid biological medicine, preparation method thereof and application thereof in tumor treatment |
| CN111956809B (en) * | 2020-08-21 | 2022-11-01 | 湖南大学 | Nucleic acid biological medicine, preparation method thereof and application thereof in tumor treatment |
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