CN107325141A - A kind of fluorescence nucleosides and preparation method thereof - Google Patents

A kind of fluorescence nucleosides and preparation method thereof Download PDF

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Publication number
CN107325141A
CN107325141A CN201710477585.XA CN201710477585A CN107325141A CN 107325141 A CN107325141 A CN 107325141A CN 201710477585 A CN201710477585 A CN 201710477585A CN 107325141 A CN107325141 A CN 107325141A
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王利民
赵恺
姚峰
熊晶晶
田禾
韩建伟
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Hongene Biotechnology Ltd
East China University of Science and Technology
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Hongene Biotechnology Ltd
East China University of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C07H19/067—Pyrimidine radicals with ribosyl as the saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1018—Heterocyclic compounds
    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1044—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1018—Heterocyclic compounds
    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1088—Heterocyclic compounds characterised by ligands containing oxygen as the only heteroatom

Abstract

The present invention relates to a kind of fluorescence nucleosides and preparation method thereof.The fluorescence nucleosides is compound shown in formula 1.Compound shown in formula 1 is to be obtained by cumarin or derivatives thereof with the reaction of corresponding uridine compound.The present invention lays a good foundation for the research of nucleic acid.In formula 1, R is hydrogen, hydroxyl, C1~C4Alkoxy, orWherein, R1And R2It is respectively and independently selected from：H or C1~C4Alkyl in it is a kind of.

Description

A kind of fluorescence nucleosides and preparation method thereof
Technical field
The present invention relates to a kind of fluorescence nucleosides and preparation method thereof, specifically, it is related to one kind by cumarin or its derivative Uridine compound of thing modification and preparation method thereof.
Background technology
At present, to the research extremely scientist in terms of nucleic acid (DNA and RNA) folding, tertiary structure, identification and function Concern.Nucleosides with fluorescence can provide effective detection means for these researchs, and (such as fluorescence nucleosides is applied to monokaryon Nucleotide polymorphism detection, nucleic acid structure and Function detection and the detection of the microenvironment of nucleic acid etc..Document is shown in： J.Am.Chem.Soc.2003,125,9296-9297, Org.Lett.2002,4,2305-2308, Chem.Commun., 2013, 49,5684-5686, J.Org.Chem.2015,80,8561-8570. etc.).
There is the nucleosides with fluorescence in nature extremely rare.In other words, most nucleosides do not have in nature Standby fluorescence, this research to nucleic acid causes great inconvenience.Therefore, how to make the nucleosides for not possessing fluorescence originally that there is fluorescence As this area urgent problem to be solved, while being also the technical problem to be solved in the invention.
The content of the invention
It is an advantage of the invention to provide a kind of structure is novel and nucleosides with fluorescence.
Nucleosides of the present invention, is compound shown in formula 1：
In formula 1, R is hydrogen (H), hydroxyl (OH), C1~C4Alkoxy, or
Wherein, R1And R2It is respectively and independently selected from：H or C1~C4Alkyl in it is a kind of.
It is another object of the present invention to provide a kind of method of compound shown in formula 1, comprises the following steps：
(1) with cumarin or derivatives thereof (compound shown in formula 2) for initiation material, during as shown in formula 2 prepared by compound The step of mesosome A (compound shown in formula 3)；
(2) the step of compound prepares intermediate B (compound shown in formula 4) as shown in formula 3；
(3) the step of compound as shown in formula 4 prepares intermediate C (compound shown in formula 5)；With,
(4) compound is reacted with 5- ioduria glycosides as shown in formula 5, the step of obtaining object (compound shown in formula 1)；
Wherein, R definition with it is described previously identical.
Brief description of the drawings
Fig. 1 are compound 1a and compound 1b UV absorption spectrogram；
Fig. 2 are compound 1a and compound 1b fluorescence emission spectrum.
Embodiment
In a preferred technical scheme of the invention,
The method of compound, specifically includes following steps shown in the formula 1 that the present invention is provided：
(1) compound shown in formula 2, potassium hydrogen persulfate (OXONE), hydrogen bromide (HBr) aqueous solution and halogenated hydrocarbons (such as dichloromethane Alkane or chloroform etc.) it is placed in reactor, kept at least 6 hours in room temperature (15 DEG C~25 DEG C, similarly hereinafter) state, then to the reactor Middle addition triethylamine, then kept at least 12 hours in room temperature state, obtain intermediate A (compound shown in formula 3)；
(2) in the case where there is inert gas (such as argon gas) existence condition, by compound shown in formula 3, palladium bichloride, cuprous iodide, Triphenylphosphine, acetonitrile, trimethyl silicane ethyl-acetylene and triethylamine are placed in reactor, small in 30 DEG C~50 DEG C states holdings at least 12 When, obtain intermediate B (compound shown in formula 4)；
(3) compound, potassium carbonate and methanol shown in formula 4 are placed in reactor, kept at least 1 hour in room temperature state, Obtain intermediate C (compound shown in formula 5)；With,
(4) in the case where there is inert gas (such as argon gas) existence condition, by compound shown in formula 5, palladium bichloride, cuprous iodide, Triphenylphosphine, acetonitrile, 5- ioduria glycosides and triethylamine are placed in reactor, are kept at least 12 hours, obtained in 50 DEG C~70 DEG C states To object.
The present invention is further elaborated by the following examples, its purpose, which is only that, is best understood from present disclosure. Therefore, the cited case is not limited the scope of the invention.
Embodiment 1
(1) preparation of intermediate (compound shown in formula 3a)：
Cumarin (0.73g, 5mmol) and Oxone (3.7g, 6mmol) are added in Schlenk bottles, argon gas protection, are added DCM dissolves (20mL), adds 2N HBr (5.5mL, 11mm01) aqueous solution, reaction solution is changed into rufous turbid solution.Room temperature is anti- Answer after 6h, then triethylamine (2.1mL, 15mmol) be slowly added dropwise, red before this during addition to disappear, can then emerge a large amount of bubbles, Solution colour is changed into green, last to be changed into micro- rubescent color again, and TLC tracking reactions (PE/EA=10: 1, v/v) to raw material point disappear, With dichloromethane extractive reaction liquid (30mL × 3), organic layer merge after with being spin-dried for after anhydrous sodium sulfate drying, crude product purified by silica gel Column chromatography purifies (leacheate：PE-PE/EA=10: 1, v/v), leacheate is collected, 0.59g white solid products are obtained after being spin-dried for (compound shown in formula 3a), yield 52.1%
1H NMR (400MHz, CDCl3)δ：8.12 (s, 1H), 7.58 (td, J=8.0Hz, 1.6Hz, 1H), 7.47 (dd, J =8.0Hz, 1.6Hz), 7.37-7.30 (m, 2H)
13C NMR (100MHz, CDCl3)δ：157.1,153.2,144.5,132.1,127.2,125.0,119.3, 116.8,111.8.
HRMS(ESI)calcd for C9H6BrO2 +([M+H]+)：224.9546, Found：224.9551.
(2) preparation of intermediate (compound shown in formula 4a)：
Under argon gas protection, compound (0.75g, 3.33mmol) shown in formula 3a, palladium bichloride (47.2mg, 0.26mmol), Cuprous iodide (49.5mg, 0.26mmol), triphenylphosphine (136.4mg, 0.52mmol) is dissolved in MeCN (30mL), under agitation Triethylamine (1.4mL, 10mmol) and trimethyl acetenyl silicon (0.56mL, 4mmol) are added, 30 DEG C~45 DEG C are then heated to Reaction, TLC tracking reactions (PE/EA=20: 1) to raw material point disappear, and are spin-dried for reaction solution, add 30mL EA and 30mL water, Extracted with EA (30mL × 3), merge organic layer, it is organic with anhydrous sodium sulfate drying after being washed with saturated common salt (30mL × 1) Layer purifies (leacheate with silica gel column chromatography after being spin-dried for：PE/EA=20: 1, v/v), obtain 0.66g yellow solids (formula 4a shownization Compound), yield 81.4%.
1H NMR (400MHz, CDCl3)δ：7.92 (s, 1H), 7.56-7.51 (m, 1H), 7.46 (dd, J=7.6Hz, 1.6Hz, 1H), 7.34-7.27 (m, 2H), 0.28 (s, 9H)
13C NMR (100MHz, CDCl3)δ：159.5,153.7,146.2,132.5,128.0,125.0,119.0, 117.1,113.1,102.4,98.3, -0.01.
HRMS(ESI)calcd for C14H15SiO2 +([M+H]+)：243.0836, Found：243.0851.
(3) preparation of intermediate (compound shown in formula 5a)：
Compound (0.27g, 1.11mmol) shown in formula 4a is dissolved in 25mL methanol, 30.8mg (0.22mmol) carbon is added Sour potassium, is stirred at room temperature after reaction 1h, is spin-dried for solvent, crude product purified by silica gel column chromatography purifying (leacheate：PE/EA=10: 1, V/v), 0.17g yellow solid products (compound shown in formula 5a), yield 89.9% are obtained.
1H NMR (400MHz, CDCl3)δ：7.96 (s, 1H), 7.59-7.54 (m, 1H), 7.49 (dd, J=7.6Hz, 1.2Hz, 1H), 7.35-7.30 (m, 1H), 3.39 (s, 1H)
13C NMR (100MHz, CDCl3)δ：159.4,153.5,146.6,132.7,127.9,125.0,118.5, 116.9,111.9,83.8,29.7.
HRMS(ESI)calcd for C11H7O2 +([M+H]+)：171.0441, Found：171.0455.
(4) preparation of target compound (compound shown in formula 1a)：
Under argon gas protection, by compound (0.13g, 0.764mmol) shown in formula 5a, palladium bichloride (10.8mg, 0.061mmol), cuprous iodide (11.6mg, 0.061mmol), triphenylphosphine (32.0mg, 0.122mmol) is dissolved in 7mL acetonitriles In, triethylamine (0.32mL, 2.29mmol) and 5- ioduria glycosides (0.28g, 0.764mmol) are added under agitation, are then heated To 50 DEG C~60 DEG C reactions, TLC tracking reactions (DCM/MeOH=10: 1) to raw material point are disappeared, and are spin-dried for reaction solution, and residue is used Silica gel column chromatography purifies (leacheate：DCM-DCM/MeOH=10: 1), 199mg target compounds (compound shown in formula 1a), production Rate 63.4%.
1H NMR (400MHz, DMSO-d6)δ：9.07 (s, 1H), 8.52 (s, 1H), 7.94 (d, J=6.4Hz, 1H), 7.68-7.64 (m, 1H), 7.46-7.39 (m, 3H), 5.85 (d, J=1.6Hz, 1H), 5.64 (s, 1H), 5.32 (s, 1H), (d, J=11.2Hz, the 1H) of 5.10 (s, 1H), 4.04-4.00 (m, 3H), 3.86 (d, J=11.2Hz, 1H), 3.69
13C NMR (100MHz, DMSO-d6)δ：160.5,152.8,150.3,149.6,146.0,145.1,131.5, 128.8,128.5,124.9,118.7,116.2,111.4,88.2,87.6,84.7,73.9,69.3,60.1,45.6.
HRMS(ESI)calcd for C20H17N2O8 +([M+H]+)：413.0979, Found：413.0990.
Embodiment 2
(1) preparation of intermediate (compound shown in formula 2b)：
4- diethylin salicylide (1.06g, 5.5mmol), diethyl malonate (1.7mL, 11mmol) and piperidines (0.7mL) is dissolved in 20mL ethanol, is heated to 80 DEG C of back flow reactions, and TLC tracking reaction to raw material point disappears, and is spin-dried for reaction solution, Residue is dissolved with 12mL acetic acid and 12mL concentrated hydrochloric acids, is then heated to 120 DEG C of back flow reactions, and reaction solution is in brownish black, reaction After 16 hours, cooling pours into reaction solution in 80mL frozen water, adds 2M NaOH aqueous solution regulation pH=5, it is seen that have a large amount of Solid is separated out, and is atropurpureus solid after precipitation.Filtering, filter cake is washed with water after the solid drying twice, obtained, obtains 1.13g purple Black solid product (compound shown in formula 2b), yield 94.2%.
1H NMR (400MHz, CDCl3)δ：7.53 (d, J=9.6Hz, 1H), 7.24 (d, J=8.8Hz, 1H), 6.56 (dd, J=8.8Hz, 2.8Hz, 1H), 6.49 (d, J=2.8Hz, 1H), 6.03 (d, J=9.6Hz), 3.41 (q, J=7.2Hz, 4H), 1.21 (t, J=7.2Hz, 6H)
(2) preparation of intermediate (compound shown in formula 3b)：
Compound (1.13g, 5.2mmol) shown in formula 2b is dissolved in 20mL acetic acid, and solution is in rufous.Under agitation dropwise The μ L (5.2mmol) of bromine 266 are added, there is white solid precipitation immediately.Filtered after reaction 3h is stirred at room temperature, obtained filter cake second Nitrile washs (20mL × 3), and 1.49g white solid products (compound shown in formula 3b), yield 96.9%. are obtained after drying
1H NMR (400MHz, DMSO-d6)δ：8.34 (s, 1H), 7.43 (d, J=8.8Hz, 1H), 6.73 (dd, J= 8.8Hz, 2.4Hz, 1H), 6.55 (d, J=2.4Hz), 3.42 (q, J=6.8Hz, 4H), 1.11 (t, J=6.8Hz, 6H)
13C NMR (100MHz, DMSO-d6)δ：157.3,155.6,150.6,145.6,128.9,109.5,108.4, 101.2,96.4,44.2,12.2.
HRMS(ESI)calcd for C13H15BrNO2 +([M+H]+)：296.0281, Found：296.0291.
(3) preparation of intermediate (compound shown in formula 4b)：
Under argon gas protection, compound (1.49g, 5.0mmol), PdCl shown in formula 3b2(44.3mg, 0.25mmol), CuI (47.6mg, 0.25mmol), PPh3(131.2mg, 0.5mmol) is dissolved in MeCN (40mL), and triethylamine is added under agitation (1.4mL, 10mmol) and trimethyl acetenyl silicon (1.4mL, 10mmol), is then heated to 45 DEG C~50 DEG C reactions, TLC tracking React (PE/EA=5: 1) to raw material point to disappear, be spin-dried for reaction solution, be subsequently added into after the dissolving of 40mL EA and 40mL water, extracted with EA Take (40mL × 3), merge organic layer, (40mL × 1) uses anhydrous sodium sulfate drying after being washed with saturated common salt, and silica gel is used after being spin-dried for Column chromatography purifies (leacheate：PE/EA=20: 1-2: 1, v/v), obtain 1.15g yellow-brown solids product (chemical combination shown in formula 4b Thing), yield 72.7%.
1H NMR (400MHz, CDCl3)δ：7.75 (s, 1H), 7.21 (d, J=8.8Hz, 1H), 6.56 (d, J=8.8Hz, 1H), (s, the 9H) of 6.46 (s, 1H), 3.41 (q, J=7.2Hz, 4H), 1.21 (t, J=7.2Hz, 6H), 0.25
13C NMR (100MHz, CDCl3)δ：160.9,156.4,151.2,146.7,129.0,109.2,108.2, 104.5,99.6,98.7,97.3,45.0,12.5,0.0.
HRMS(ESI)calcd for C18H24SiNO2 +([M+H]+)：314.1571, Found：314.1577.
(4) preparation of intermediate (compound shown in formula 5b)：
Compound (1.15g, 3.67mmol) shown in formula 4b is dissolved in 35mL methanol, 101mg (0.73mmol) carbon is added Sour potassium, is stirred at room temperature reaction 16h, TLC tracking reaction and is disappeared to raw material point, be spin-dried for reaction solution, residue silica gel column layer Analyse (leacheate：PE/EA=10: 1-5: 1) purify, obtain 0.56g orange solid products (compound shown in formula 5b), yield 62.8%.
1H NMR (400MHz, CDCl3)δ：7.76 (s, 1H), 7.22 (d, J=8.8Hz, 1H), 6.58 (dd, J=8.8Hz, 2.4Hz, 1H), 6.44 (d, J=2.4Hz, 1H), 3.42 (q, J=7.2Hz, 4H), 3.26 (s, 1H), 1.21 (t, 7.2Hz, 6H).
13C NMR (100MHz, CDCl3)δ：161.2,156.4,151.4,147.0,129.1,109.3,108.0, 103.3,97.2,81.1,78.6,45.0,12.4.
HRMS(ESI)calcd for C15H16NO2 +([M+H]+)：242.1181, Found：242.1185.
(5) preparation of target compound (compound shown in formula 1b)：
Compound (0.556g, 2.3mmol) shown in formula 5b, 5- ioduria glycosides (0.853g, 2.3mmol), PdCl2(20.4mg, 0.12mmol), CuI (21.9mg, 0.12mmol) and PPh3(60.3mg, 0.23mmol) is dissolved in 23mL acetonitriles, under agitation Triethylamine 0.96mL (6.9mmol) is added, 60 DEG C~70 DEG C reaction 24h is then heated to, is spin-dried for solvent, residue silica gel Column chromatography purifies (leacheate：DCM/MeOH=10: 1, v/v), obtain 316.7mg brown solid (target compounds：Formula 1b Shown compound), yield 28.5%.
1H NMR (400MHz, DMSO-d6)δ：8.95 (s, 1H), 8.28 (s, 1H), 7.64 (d, J=8.8Hz, 1H), 7.12 (s, 1H), 6.76 (dd, J=8.8Hz, 2.4Hz, 1H), 6.56 (d, J=2.4Hz), 5.86 (d, J=2.0Hz, 1H), 5.60 (d, J=4.4Hz, 1H), 5.29 (t, J=5.2Hz, 1H), 5.07 (d, J=5.6Hz, 1H), 4.03-3.97 (m, 3H), 3.88- (t, J=6.8Hz, the 6H) of 3.83 (m, 1H), 3.70-3.66 (m, 1H), 3.45 (q, J=6.8Hz, 4H), 1.14
13C NMR (100MHz, DMSO-d6)δ：170.6,158.0,155.6,154.0,151.3,149.4,138.4, 138.1,130.6,109.8,107.7,107.1,107.0,101.6,96.1,91.5,84.1,74.8,68.0,59.6,44.2, 12.3.
HRMS(ESI)calcd for C24H26N3O8 +([M+H]+)：484.1714, Found：484.1720.
Embodiment 3
Ultraviolet and fluorometric investigation
In 10mL volumetric flasks, compound 1a and compound 1b are configured to 1 × 10 respectively-3Mol/L solution, solvent is Dioxane, is then diluted to 1 × 10 in cuvette-5Carry out absorbing the survey with fluorescence spectrum after mol/L solution 2mL Examination.When testing fluorescence, excited using the maximum absorption wavelength of compound, as a result see Fig. 1 and Fig. 2.
As shown in Figure 1：Compound 1a uv-absorption maximum wavelength is 380nm, compound 1b maximal ultraviolet absorption ripple A length of 433nm.
As shown in Figure 2, compound 1a maximum emission wavelength is 448nm, compound 1b maximum fluorescence emission ripple A length of 479nm, shows that compound 1a and compound 1b have good photoluminescent property.

Claims (8)

1. a kind of fluorescence nucleosides, it is compound shown in formula 1：
In formula 1, R is hydrogen, hydroxyl, C1~C4Alkoxy, or
Wherein, R1And R2It is respectively and independently selected from：H or C1~C4Alkyl in it is a kind of.
2. a kind of method for preparing fluorescence nucleosides described in claim 1, it is characterised in that methods described comprises the following steps：
(1) using compound shown in formula 2 as initiation material, as shown in formula 2 shown in preparation of compounds of formula 3 the step of compound；
(2) as shown in formula 3 shown in preparation of compounds of formula 4 the step of compound；
(3) as shown in formula 4 shown in preparation of compounds of formula 5 the step of compound；With,
(4) compound is reacted with 5- ioduria glycosides as shown in formula 5, the step of obtaining object；
Wherein, R definition is identical with described in claim 1.
3. method as claimed in claim 2, it is characterised in that wherein, the step (1) specifically includes following steps：
Compound, potassium hydrogen persulfate, aqueous solution of hydrogen bromide and halogenated hydrocarbons are placed in reactor shown in formula 2, are kept in room temperature state At least 6 hours, then triethylamine is added into the reactor, then kept at least 12 hours in room temperature state, obtain chemical combination shown in formula 3 Thing.
4. method as claimed in claim 3, it is characterised in that wherein described halogenated hydrocarbons is dichloromethane or chloroform.
5. method as claimed in claim 2, it is characterised in that wherein, the step (2) specifically includes following steps：
In the case where there is inert gas existence condition, by compound, palladium bichloride, cuprous iodide, triphenylphosphine, acetonitrile, front three shown in formula 3 Base silicon substrate acetylene and triethylamine are placed in reactor, are kept at least 12 hours in 30 DEG C~50 DEG C states, are obtained chemical combination shown in formula 4 Thing.
6. method as claimed in claim 2, it is characterised in that wherein, the step (3) specifically includes following steps：
Compound, potassium carbonate and methanol shown in formula 4 are placed in reactor, is kept at least 1 hour in room temperature state, obtains formula 5 Shown compound.
7. method as claimed in claim 2, it is characterised in that wherein, the step (4) specifically includes following steps：
In the case where there is inert gas existence condition, by compound shown in formula 5, palladium bichloride, cuprous iodide, triphenylphosphine, acetonitrile, 5- iodine Uridine and triethylamine are placed in reactor, are kept at least 12 hours in 50 DEG C~70 DEG C states, are obtained object.
8. such as the methods described of claim 5 or 7, it is characterised in that wherein, the inert gas is argon gas.
CN201710477585.XA 2017-06-21 2017-06-21 A kind of fluorescence nucleosides and preparation method thereof Pending CN107325141A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103484106A (en) * 2013-09-05 2014-01-01 上海交通大学 Four-color fluorescence labeling reversible terminal and use thereof in DNA (Deoxyribonucleic Acid) sequencing
CN106699826A (en) * 2016-12-20 2017-05-24 江南大学 Nucleoside derivative and preparation method thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103484106A (en) * 2013-09-05 2014-01-01 上海交通大学 Four-color fluorescence labeling reversible terminal and use thereof in DNA (Deoxyribonucleic Acid) sequencing
CN106699826A (en) * 2016-12-20 2017-05-24 江南大学 Nucleoside derivative and preparation method thereof

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Application publication date: 20171107