CN106928295B - One kind has anthraquinone glycoconjugate of cyclic structure and preparation method thereof and the application in environment measuring - Google Patents
One kind has anthraquinone glycoconjugate of cyclic structure and preparation method thereof and the application in environment measuring Download PDFInfo
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- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
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- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
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Abstract
Application the invention discloses a kind of anthraquinone glycoconjugate with cyclic structure and preparation method thereof and in environment measuring, belongs to the synthesis technical field of pharmaceutical intermediate and fluorescent probe molecule.Technical solution of the present invention main points are as follows:
Description
Technical field
The invention belongs to the synthesis technical fields of pharmaceutical intermediate and fluorescent probe molecule, and in particular to one kind has ring-type
Anthraquinone glycoconjugate of structure and preparation method thereof and the application in environment measuring.
Background technique
Metal ion and the fields such as life science, environmental science, medicine have it is inseparable contact, it is identified
It is the hot subject of chemistry, biology, clinical biochemical and the numerous research fields of environmentology with detection.Wherein fluorescence detection has
There are easy method, sensitivity and selectivity height and real-time, on-line checking may be implemented.Therefore, it is repaired on host molecule
Decorations fluorogen is quite paid attention to the research for constructing supermolecule fluorescence probe metal ion for identification.
Anthraquinone analog compound is big ring conjugated system, has planar structure, the moderate, photostability with fluorescence emission wavelengths
Good and high luminous efficiency and other features, more important is its fluorescence and UV absorption wavelength to be both present in visible region.Due to can be with
The anthraquinone derivative that complexation of metal ions, amino and hydroxyl replace is also widely used in analytical chemistry as chromophore.From
Anthraquinone derivative derived from hydroxy terminal and Action of Metal Ions are converted into complicated compound and have obtained extensively as chelating agent
Chemical activator.
1,2,3- triazole compound is a kind of with the active penta azacyclo compound of important biomolecule, is amido bond
Isostere, all than 1,2,4- triazole compound under the conditions ofs metabolic conversion, redox, soda acid and high temperature etc.
With higher stability.Huisgen 1,3- cycloaddition reaction between the azide and end alkynes of Cu (I) catalysis in recent years
With generate the disubstituted 1,2,3- triazole compound of 1,4- attract synthetic organic chemistry, polymer science, material science,
Biology and peptide attract attention.Potential drug based on 1,2,3- triazole compound includes anticarcinogen CAI and known nucleosides
Derivative TSAO is non-nucleoside reverse transcriptase inhibitor, these compounds all or in clinical test.1,2,3- tri-
Nitrogen azole compounds gradually come into the picture as the potential ligand that metal ion combines.Triazole is found by consulting literatures
Base optical probe usually have certain cation it is highly selective, while and ion combination it is relatively firm.But this kind of probe
Dissolubility is poor, it usually needs is detected in organic solvent.
Saccharide compound is because its own structure has the characteristics that hydroxyl, oxygen atom and chirality, simultaneously because carbohydrate point
Hypotoxicity, biofacies content height and the good solubility in water of son, therefore grinding for optical sensor is burnt about glycosyl chemistry
Study carefully becomes hot spot gradually.And glycosyl chemical probe is due to its good aqueous solubility and excellent biofacies content, it also will be in cell
Label and bio-imaging field have potential application.Currently, the chemical probe constructed using carbohydrate molecule as core skeleton,
Had the glycosyl chemical probe for largely connecting different optical notifications group be applied to detect each metal ion species, anion or
Person's small molecule.
Summary of the invention
The technical problem to be solved by the present invention is to provide a kind of anthraquinone glycoconjugate with cyclic structure and its preparation sides
Method, this method are devised a series of containing triazole using the water solubility of anthraquinone, the metal combination of triazole and saccharide compound
The anthraquinone analog compound of sulphur bridge cyclic structure, and fluorescence activity test is carried out to it, it can preferably be applied to ring as the result is shown
The detection of heavy metal ion in border.
The present invention adopts the following technical scheme that there is one kind the anthraquinone sugar of cyclic structure to be conjugated to solve above-mentioned technical problem
Object, it is characterised in that have the following structure:
A wherein integer of the n between 1-4.
The preparation method of anthraquinone glycoconjugate of the present invention with cyclic structure, it is characterised in that specific steps
Are as follows:
(1) monosaccharide obtains full acetyl monosaccharide compounds one with acetic acid anhydride reactant in the presence of alkali, and wherein monosaccharide is grape
Sugar, galactolipin, mannose, acetylglucosamine, acetylamino galactosamine or 1,5-anhydroglucitol, alkali are sodium acetate, methanol
Sodium or pyridine；
(2) full acetyl monosaccharide compounds one react to obtain compound two with the bromo- 6- hexanol of 1- under the action of an acid, wherein acid
For hydrogen chloride gas, boron trifluoride ether solution, p-methyl benzenesulfonic acid, acetic acid, dibrominated zinc, silica or copper sulphate；
(3) compound two and reaction of sodium azide obtain compound three；
(4) compound three in the presence of alkali protect and react under alkaline condition with paratoluensulfonyl chloride by deacetylation
To compound four, wherein alkali is sodium methoxide, potassium carbonate, sodium hydroxide or potassium hydroxide；
(5) compound four and thioacetic acid nak response obtain compound five；
(6) anthraquinone reacts to obtain compound six with propargyl bromide；
(7) compound five reacts to obtain compound seven under the action of SODIUM ASCORBATE and mantoquita with compound six,
Middle mantoquita is cupric sulfate pentahydrate, cuprous iodide or stannous chloride；
(8) compound seven is through being deprotected the anthraquinone glycoconjugate for obtaining target product and having cyclic structure.
The preparation method of anthraquinone glycoconjugate of the present invention with cyclic structure, it is characterised in that specific steps
Are as follows:
The synthesis of (1) 1,2,3,4,6- five-O- acetyl group-β-D- glucopyranoses, by DEXTROSE ANHYDROUS in sodium acetate
It acts on lower and acetic anhydride and obtains five-O- acetyl group-β-D- glucopyranose of 1,2,3,4,6- in 140 DEG C of heating reflux reactions；
The synthesis of (2) 2,3,4,6- tetra--O- acetyl group-(6- bromine hexyl)-β-D- glucopyranoside, by 1,2,3,4,6-
Five-O- acetyl group-β-D- glucopyranoses withMethylene chloride is added in molecular sieve under nitrogen protection, add the bromo- 6- of 1- oneself
Boron trifluoride ether is added under ice bath, nitrogen protection and reacts to obtain tetra--O- acetyl group of 2,3,4,6--(6- bromine hexyl)-β-for alcohol
D- glucopyranoside；
The synthesis of (3) 2,3,4,6- tetra--O- acetyl group-(6- nitrine hexyl)-β-D- glucopyranoside, by 2,3,4,6-
Four-O- acetyl group-(6- bromine hexyl)-β-D- glucopyranoside is dissolved in N,N-dimethylformamide with sodium azide in 60 DEG C
Reaction obtains tetra--O- acetyl group of 2,3,4,6--(6- nitrine hexyl)-β-D- glucopyranoside；
(4) 2,3,4- tri--O- benzoyl -6-O- p-toluenesulfonyl (6- nitrine hexyl)-β-D- glucopyranoside
Synthesis, 2,3,4,6- tetra--O- acetyl group-(6- nitrine hexyl)-β-D- glucopyranoside is dissolved in methanol, methanol is passed through
It is 8-9 that sodium, which adjusts pH, and it is 7 that acidic resins are added after fully reacting and adjust pH, and the grease after filtration drying is dissolved in pyridine, and
The pyridine solution of paratoluensulfonyl chloride is added under condition of ice bath, adds 4-dimethylaminopyridine and reacts to obtain 2,3,4- tri--O-
Benzoyl -6-O- p-toluenesulfonyl (6- nitrine hexyl)-β-D- glucopyranoside；
The synthesis of (5) 2,3,4- tri--O- benzoyl -6- sulphur acetyl group (6- nitrine hexyl)-β-D- glucopyranosides,
2,3,4- tri--O- benzoyl -6-O- p-toluenesulfonyl (6- nitrine hexyl)-β-D- glucopyranoside is dissolved in acetone
It reacts to obtain tri--O- benzoyl -6- sulphur acetyl group (6- nitrine of 2,3,4- in 65 DEG C with thioacetic acid potassium and tetrabutylammonium iodide
Hexyl)-β-D- glucopyranoside；
The synthesis of (6) 1,8- bis--O- propargyls-anthraquinone, by 1,8- dihydroxy anthraquinone be dissolved in n,N-Dimethylformamide with
Potassium carbonate and bromo- 1 propine of 3- obtain bis--O- propargyl of 1,8--anthraquinone in room temperature reaction；
(7) synthesis of the anthraquinone glycoconjugate with protecting group, by 2,3,4- tri--O- benzoyl -6- sulphur acetyl group (6-
Nitrine hexyl)-β-D- glucopyranoside and bis--O- propargyl of 1,8--anthraquinone be dissolved in SODIUM ASCORBATE and cupric sulfate pentahydrate
Under the action of be protected from light in 55 DEG C under the conditions of reaction obtain the anthraquinone glycoconjugate with protecting group；
(8) synthesis of the anthraquinone glycoconjugate with cyclic structure, by the anthraquinone glycoconjugate with protecting group through remove-insurance
Shield obtains the anthraquinone glycoconjugate that target product has cyclic structure, and wherein protecting group is acetyl group, benzoyl or benzyl, takes off
The condition of acetyl or benzoyl base is the condition of debenzylation under the action of sodium methoxide, potassium carbonate, triethylamine or sodium hydroxide
For under the action of hydrogen/palladium carbon or hydrogen/palladium dydroxide.
The preparation method of anthraquinone glycoconjugate of the present invention with cyclic structure, it is characterised in that in synthesis process
Reaction equation are as follows:
Wherein R3For Ac, Bz or Bn.
Application of the anthraquinone glycoconjugate of the present invention with cyclic structure in environment measuring, this has cyclic annular knot
The anthraquinone glycoconjugate of structure is used for as fluorescence probe in neutral DMF-H2It realizes in O system to Cr3+Quantitative detection.
Compared with the prior art, the invention has the following beneficial effects: operation of the present invention is easy, reaction condition is mild, used
Reagent is industrial common agents, is suitble to a large amount of preparations of industrialization；Synthetic route is succinct, can be dissipated by changing some monosaccharide
Formula obtains anthraquinone glycoconjugate largely with cyclic structure, and carries out fluorescence activity test to it, this has as the result is shown
The anthraquinone glycoconjugate of cyclic structure can preferably be applied to the detection of heavy metal ion in environment.
Specific embodiment
Above content of the invention is described in further details by the following examples, but this should not be interpreted as to this
The range for inventing above-mentioned theme is only limitted to embodiment below, and all technologies realized based on above content of the present invention belong to this hair
Bright range.
Embodiment
1, the embodiment of the present invention (by taking compound A as above as an example) presented below:
(1) synthesis of five-O- acetyl group-β-D- glucopyranose 1 of 1,2,3,4,6-
Take DEXTROSE ANHYDROUS (20g, 0.111mol) and sodium acetate (4.552g, 0.056mol) in 250mL round-bottomed flask,
Acetic anhydride (105mL, 1.11mol) is added and is heated to reflux stirring 2h in 140 DEG C.Reaction pours into 300mL ice water after being cooled to room temperature
In, reaction solution is filtered after product is largely precipitated, filter cake is washed with massive laundering to neutrality, and vacuum drying can obtain white solid
1,2,3,4,6- five-O- acetyl group-β-D- glucopyranose 1 (39.3g, 98%) of compound.
(2) synthesis of tetra--O- acetyl group of 2,3,4,6--(6- bromine hexyl)-β-D- glucopyranoside 2
Take five-O- acetyl group-β-D- glucopyranose 1 (2g) of 1,2,3,4,6- and appropriateMolecular sieve is in round-bottomed flask
In, methylene chloride is added under nitrogen protection, is stirring evenly and then adding into the bromo- 6- hexanol 0.74mL of 1- and is dripped under ice bath, nitrogen protection
Add boron trifluoride ether 2.5mL, ice bath is removed after 1h to reacting at room temperature, after TLC monitors raw material fully reacting, adds water to terminate anti-
It answers, after being diluted with q. s. methylene chloride, with saturation NaHCO3It is about 7 that solution, which adjusts pH, methylene chloride extraction, saturated common salt washing
Wash anhydrous Na2SO4It dries, filters, is concentrated, 2,3,4,6- tetra--O- acetyl of compound as white solid can be obtained in pillar layer separation
Base-(6- bromine hexyl)-β-D- glucopyranoside 2 (990.3mg, 43%).
1H NMR(CDCl3, 400MHz) and δ 5.20 (t, J=9.6Hz, 1H), 5.09 (t, J=9.6Hz, 1H), 4.98 (dd, J
=9.6,8.0Hz, 1H), 4.49 (d, J=8.0Hz, 1H), 4.26 (dd, J=12.4,4.8Hz, 1H), 4.13 (dd, J=
12.4,2.4Hz, 1H), 3.87 (dt, J=9.6,6.4Hz 1H), 3.70-3.67 (m, 1H), 3.50-3.45 (m, 1H), 3.40
(t, J=6.8Hz, 2H), 2.09 (s, 3H), 2.04 (s, 3H), 2.02 (s, 3H), 2.01 (s, 3H), 1.89-1.79 (m, 2H),
1.62-1.53(m,2H),1.48-1.40(m,2H),1.38-1.32(m,2H).13C NMR(CDCl3,400MHz)δ170.9,
170.5,169.6,169.4,100.9,73.0,71.9,71.4,70.1,68.5,62.1,33.9,32.75,29.3,27.9,
25.1,20.9,20.8,20.8,20.8。
(3) synthesis of tetra--O- acetyl group of 2,3,4,6--(6- nitrine hexyl)-β-D- glucopyranoside 3
Take tetra--O- acetyl group of 2,3,4,6--(6- bromine hexyl)-β-D- glucopyranoside 2 (400mg) in round-bottomed flask
In, it is dissolved with n,N-Dimethylformamide (DMF), sodium azide 306mg is added, in 60 DEG C of heating stirrings.It is anti-that TLC monitors raw material
It is cooled to room temperature after answering completely, 20mL distilled water is added, water washing, anhydrous Na are distilled in ethyl acetate extraction2SO4It dries, filters,
Concentration, carrying out separation with column chromatography can be obtained 2,3,4,6- tetra--O- acetyl group of compound as white solid-(6- nitrine hexyl)-
β-D- glucopyranoside 3 (330mg, 93%).
1H NMR(CDCl3, 400MHz) and δ 5.20 (t, J=9.6Hz, 1H), 5.08 (t, J=9.6Hz, 1H), 4.98 (dd, J
=9.4,8.2Hz, 1H), 4.48 (d, J=7.6Hz, 1H), 4.26 (dd, J=12.4,4.4Hz, 1H), 4.13 (dd, J=
12.4,2.4Hz, 1H), 3.90-3.84 (m, 1H), 3.70-3.66 (m, 1H), 3.50-3.43 (m, 1H), 3.25 (t, J=
6.8Hz,2H),2.08(s,3H),2.03(s,3H),2.02(s,3H),2.00(s,3H),1.60-1.55(m,4H),1.40-
1.32(m,4H).13C NMR(CDCl3,400MHz)δ170.9,170.5,169.6,169.5,100.9,72.9,71.9,71.4,
70.1,68.5,62.1,51.5,29.4,28.9,26.5,25.5,20.9,20.8,20.8,20.8。
(4) 2,3,4- tri--O- benzoyl -6-O- p-toluenesulfonyl (6- nitrine hexyl)-β-D- glucopyranoside 4
Synthesis
Take tetra--O- acetyl group of 2,3,4,6--(6- nitrine hexyl)-β-D- glucopyranoside 3 (415mg) in round-bottomed flask
Middle to be dissolved with methanol, it is 8-9 that the sodium methoxide solution that 1mol/L is added, which adjusts pH, is stirred at room temperature.Raw material reacts after TLC monitors 0.5h
Completely, it is about 7 that acidic resins, which are added, and adjust pH, filtering, is spin-dried for doing in next step after being dried in vacuo after filtrate.After taking vacuum drying
Grease in a round bottom flask, be slowly added under ice bath after pyridinium dissolution paratoluensulfonyl chloride pyridine solution (550mg,
2.874mmol), 4-dimethylaminopyridine (DMAP, 88mg) is added, is stirred at room temperature.After TLC monitors raw material fully reacting, ice
Bath is lower to be added dropwise 0.66mL chlorobenzoyl chloride, is stirred at room temperature to fully reacting.It is spin-dried for pyridine, carrying out separation with column chromatography can be obtained nothing
Color oily compounds 2,3,4- tri--O- benzoyl -6-O- p-toluenesulfonyl (6- nitrine hexyl)-β-D- glucopyranose
Glycosides 4 (626mg, 93%).
1H NMR(CDCl3,400MHz)δ7.96-7.91(m,2H),7.88-7.82(m,2H),7.81-7.77(m,2H),
7.72 (d, J=8.4Hz, 2H), 7.56-7.49 (m, 2H), 7.44-7.35 (m, 5H), 7.30-7.24 (m, 2H), 7.22 (d, J
=8.0Hz, 2H), 5.83 (t, J=9.6Hz, 1H), 5.43 (dd, J=10.0,8.0Hz, 1H), 5.36 (t, J=9.6Hz,
1H), 4.75 (d, J=8.0Hz, 1H), 4.24-4.15 (m, 2H), 4.08-4.03 (m, 1H), 3.89 (dt, J=9.6,6.0Hz,
1H), 3.51-3.48 (m, 1H), 3.08 (t, J=6.8Hz, 2H), 2.37 (s, 3H), 1.57-1.46 (m, 2H), 1.37-1.31
(m,2H),1.26-1.18(m,4H).13C NMR(CDCl3,400MHz)δ165.8,165.3,165.0,145.1,133.7,
133.4,133.4,132.3,129.9,129.8,129.3,128.8,128.6,128.5,128.4,128.1,101.1,72.7,
72.3,71.7,70.2,69.5,68.4,51.3,29.3,28.7,26.4,25.5,21.8。
(5) synthesis of 2,3,4- tri--O- benzoyl -6- sulphur acetyl group (6- nitrine hexyl)-β-D- glucopyranoside 5
Take 2,3,4- tri--O- benzoyl -6-O- p-toluenesulfonyl (6- nitrine hexyl)-β-D- glucopyranoside 4
(600mg) in a round bottom flask, thioacetic acid potassium 362mg and tetrabutylammonium iodide 30mg is added in acetone solution, flows back in 65 DEG C
Stirring.After TLC monitors raw material fully reacting, it is cooled to room temperature, is spin-dried for acetone, yellow oily chemical combination can be obtained in pillar layer separation
Object 2,3,4- tri--O- benzoyl -6- sulphur acetyl group (6- nitrine hexyl)-β-D- glucopyranoside 5 (500mg, 96%).
1H NMR(CDCl3, 400MHz) and δ 7.99-7.91 (m, 4H), 7.82 (d, J=7.6Hz, 2H), 7.52 (t, J=
7.2Hz, 2H), 7.43-7.36 (m, 5H), 7.27 (t, J=7.6Hz, 2H), 5.83 (t, J=9.6Hz, 1H), 5.51-5.42
(m, 2H), 4.75 (d, J=8.0Hz, 1H), 3.95-3.89 (M, 2H), 3.54 (dt, J=9.6,6.4Hz, 1H), 3.45 (dd, J
=14.4,2.8Hz, 1H), 3.11-3.03 (m, 3H), 2.34 (s, 3H), 1.59-1.49 (m, 2H), 1.39-1.30 (m, 2H),
1.27-1.20(m,4H).13C NMR(CDCl3,400MHz)δ194.8,165.9,165.6,165.1,133.5,133.3,
133.3,129.9,129.8,129.8,129.4,129.0,128.9,128.5,128.5,128.4,101.2,73.5,72.9,
72.0,71.9,70.1,51.3,30.7,30.5,29.3,28.7,26.4,25.5。
(6) bis--O- propargyl of 1,8--anthraquinone 6 synthesis
Take 1.8- dihydroxy anthraquinone (2.013g) in a round bottom flask, carbon is added in n,N-Dimethylformamide (DMF) dissolution
It is stirred at room temperature after the sour bromo- 1- propine 2.6mL of potassium 5.96g and 3-, after TLC monitors raw material fully reacting, with saturated ammonium chloride tune Ph
After about 7, water washing, anhydrous Na are distilled in methylene chloride extraction2SO4It dries, filters, is concentrated, column chromatography, which carries out separation, to be obtained
To yellow solid compound 1, bis--O- propargyl of 8--anthraquinone 6 (1.84g, 80%).
1H NMR(CDCl3, 400MHz) and δ 7.92 (dd, J=7.6,0.8Hz, 2H), 7.67 (t, J=8.0Hz, 2H), 7.50
(dd, J=8.4,0.8Hz, 2H), 4.94 (s, 2H), 4.94 (s, 2H), 2.55 (t, J=2.4Hz, 2H).
(7) synthesis of the anthraquinone glycoconjugate 7 with protecting group
Take 2,3,4- tri--O- benzoyl -6- sulphur acetyl group (6- nitrine hexyl)-β-D- glucopyranoside 5 (136mg)
In a round bottom flask with 1,8-, bis--O- propargyl-anthraquinone 6 (30.3mg), the H for being 1:1 with volume ratio2The mixed solvent of O and THF
30 μ of L-AA sodium salt of cupric sulfate pentahydrate 3.6mg and 1mol/L is added in 55 DEG C of heating stirrings under the conditions of being protected from light in dissolution
L, TLC monitor raw material 2,3,4- tri--O- benzoyl -6- sulphur acetyl group (6- nitrine hexyl)-β-D- glucopyranoside 5 and 1,
After bis--O- propargyl of 8- -6 fully reacting of anthraquinone, distilled water is added, water washing, anhydrous Na are distilled in ethyl acetate extraction2SO4It is dry
It is dry, it filters, concentration, column chromatography, which carries out separation, can be obtained the anthraquinone glycoconjugate 7 that yellow solid compound has protecting group
(150mg, 96%).
1H NMR(CDCl3, 600MHz) and δ 7.95 (d, J=7.6Hz, 4H), 7.92 (d, J=7.6Hz, 4H), 7.85 (d, J
=7.6Hz, 2H), 7.79 (d, J=7.6Hz, 4H), 7.71 (s, 2H), 7.60 (d, J=7.8Hz, 2H), 7.54-7.50 (m,
4H), 7.46 (t, J=7.2Hz, 2H), 7.43-7.37 (m, 6H), 7.34 (t, J=7.8Hz, 4H), 7.26 (t, J=5.2Hz,
4H), 5.81 (t, J=9.6Hz, 2H), 5.49-5.41 (m, 8H), 4.74 (d, J=7.8Hz, 2H), 4.14 (t, J=7.2Hz,
4H), 3.97-3.82 (m, 4H), 3.57-3.48 (m, 2H), 3.43 (dd, J=14.2,2.8Hz, 2H), 3.07 (dd, J=
14.4,7.8Hz,2H),2.32(s,6H),1.65-1.59(m,4H),1.53-1.40(m,4H),1.24-1.20(m,4H),
1.17-1.13(m,4H).13C NMR(CDCl3,600MHz)δ194.7,192.7,183.7,182.7,165.8,165.6,
165.1,158.0,143.8,134.9,134.1,133.5,133.4,133.3,129.9,129.8,129.8,129.4,
129.1,128.9,128.5,128.5,128.4,125.0,123.3,121.1,120.1,101.2,73.5,72.9,72.1,
71.9,69.9,64.1,50.2,30.7,30.5,30.1,29.2,26.1,25.4。
(8) synthesis of the anthraquinone glycoconjugate 8 with cyclic structure
It takes the anthraquinone glycoconjugate 7 (34mg) with protecting group in a round bottom flask, is dissolved with methanol, add the first of 1mol/L
It is 10, after raw material fully reacting is stirred at room temperature that sodium alkoxide, which adjusts pH, and it is about 7 that acidic resins tune pH, which is added, and vacuum filter is spin-dried for filtrate
Obtain yellow solid.Methylene chloride washing finally obtains the anthraquinone glycoconjugate 8 that target product yellow solid has cyclic structure
(17.5mg, 95%).
1H NMR(DMSO,600MHz)δ8.49(s,2H),8.23(s,2H),7.75-7.67(m,4H),5.41(s,4H),
5.33 (s, 4H), 5.15 (s, 2H), 4.38-4.33 (m, 4H), 4.12 (d, J=7.8Hz, 2H), 3.71-3.66 (m, 2H),
3.34-3.26 (m, 4H), 3.19-3.13 (m, 4H), 2.96 (dd, J=16.8,8.4Hz, 4H), 2.79 (dd, J=13.2,
9.6Hz,2H),1.86-1.72(m,4H),1.51-1.41(m,4H),1.33-1.26(m,4H),1.24-1.17(m,4H).13C
NMR(DMSO,600MHz)δ183.1,181.0,166.3,166.3,157.5,157.4,142.5,142.3,134.2,134.1,
124.7,124.5,124.1,124.0,121.2,121.0,118.9,118.8,103.0,102.9,76.5,76.4,74.3,
74.1,73.5,73.5,73.2,73.1,68.7,68.6,63.0,62.5,49.4,48.6,29.8,29.7,29.1,25.7,
25.6,25.0,24.9.ESI(+)-HRMS(m/z):[M+Na]+calcd.for C44H56N6O14S2979.3188, found
979.3172)。
Other anthraquinone triazole cyclic analogs can synthesize acquisition by the above design route.
2, acquired part of compounds structure
Series one:
Series two:
Series three:
3, the fluorescence activity data analysis of part of compounds Preliminary Determination
The present embodiment is with ultraviolet and fluorescence to anthraquinone glycoconjugate I, II and III system with cyclic structure of all synthesis
The compound of column is characterized.The results show that in neutral DMF-H2Cr is added in O system3+The fluorescence of probe molecule can be made strong
Degree greatly enhances, especially I-4, I-8, II-6, II-7, III-2 and III-6, the fluorescence intensity change and Cr of system3+Concentration exists
1×10-4-1×10-6It is in a linear relationship within the scope of mol/L, therefore the anthraquinone glycoconjugate with cyclic structure synthesized can be with
It realizes in DMF-H2To Cr in O system3+Quantitative detection.
Embodiment above describes basic principles and main features of the invention and advantage, the technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (4)
1. the anthraquinone glycoconjugate that one kind has cyclic structure, it is characterised in that have the following structure:
A wherein integer of the n between 1-4.
2. a kind of preparation method of the anthraquinone glycoconjugate described in claim 1 with cyclic structure, it is characterised in that specific
Step are as follows:
(1) monosaccharide obtains full acetyl monosaccharide compounds one with acetic acid anhydride reactant in the presence of alkali, and wherein monosaccharide is glucose, alkali
For sodium acetate, sodium methoxide or pyridine；
(2) full acetyl monosaccharide compounds one react to obtain compound two with the bromo- 6- hexanol of 1- under the action of an acid, wherein acid is salt
Acid gas, boron trifluoride ether solution, p-methyl benzenesulfonic acid, acetic acid, dibrominated zinc, silica or copper sulphate；
(3) compound two and reaction of sodium azide obtain compound three；
(4) compound three in the presence of alkali deacetylation protection and under alkaline condition with paratoluensulfonyl chloride reaction
Object four is closed, wherein alkali is sodium methoxide, potassium carbonate, sodium hydroxide or potassium hydroxide；
(5) compound four and thioacetic acid nak response obtain compound five；
(6) anthraquinone reacts to obtain compound six with propargyl bromide；
(7) compound five reacts to obtain compound seven under the action of SODIUM ASCORBATE and mantoquita with compound six, wherein copper
Salt is cupric sulfate pentahydrate, cuprous iodide or stannous chloride；
(8) compound seven is through being deprotected the anthraquinone glycoconjugate for obtaining target product and having cyclic structure；
Wherein, as shown in Equation 1, as shown in Equation 2, compound three is as shown in Equation 3, compound four such as formula 4 for compound two for compound one
Shown, as shown in Equation 5, as shown in Equation 6, compound seven as shown in Equation 7, has the anthraquinone of cyclic structure to compound six to compound five
Glycoconjugate is as shown in Equation 8；
Wherein R3For Bz, n=4.
3. the preparation method of the anthraquinone glycoconjugate according to claim 2 with cyclic structure, it is characterised in that specific
Step are as follows:
The synthesis of (1) 1,2,3,4,6- five-O- acetyl group-β-D- glucopyranoses, by DEXTROSE ANHYDROUS sodium acetate effect
Lower and acetic anhydride obtains five-O- acetyl group-β-D- glucopyranose of 1,2,3,4,6- in 140 DEG C of heating reflux reactions；
The synthesis of (2) 2,3,4,6- tetra--O- acetyl group -1-O- (6- bromine hexyl)-β-D- glucopyranoside, by 1,2,3,4,6-
Five-O- acetyl group-β-D- glucopyranoses withMethylene chloride is added in molecular sieve under nitrogen protection, add the bromo- 6- of 1- oneself
Alcohol be added under ice bath, nitrogen protection boron trifluoride ether react to obtain tetra--O- acetyl group -1-O- of 2,3,4,6- (6- bromine oneself
Base)-β-D- glucopyranoside；
The synthesis of (3) 2,3,4,6- tetra--O- acetyl group -1-O- (6- nitrine hexyl)-β-D- glucopyranoside, by 2,3,4,6-
Four-O- acetyl group -1-O- (6- bromine hexyl)-β-D- glucopyranoside be dissolved in N,N-dimethylformamide with sodium azide in
60 DEG C of reactions obtain 2,3,4,6- tetra--O- acetyl group -1-O- (6- nitrine hexyl)-β-D- glucopyranoside；
(4) 2,3,4- tri--O- benzoyl -6-O- p-toluenesulfonyl -1-O- (6- nitrine hexyl)-β-D- glucopyranoside
Synthesis, 2,3,4,6- tetra--O- acetyl group -1-O- (6- nitrine hexyl)-β-D- glucopyranoside is dissolved in methanol, is passed through
It is 8-9 that sodium methoxide, which adjusts pH, and it is 7 that acidic resins are added after fully reacting and adjust pH, and the grease after filtration drying is dissolved in pyridine,
And the pyridine solution of paratoluensulfonyl chloride is added under condition of ice bath, it adds 4-dimethylaminopyridine and reacts to obtain 2,3,4-
Three-O- benzoyl -6-O- p-toluenesulfonyl -1-O- (6- nitrine hexyl)-β-D- glucopyranosides；
(5) conjunction of 2,3,4- tri--O- benzoyl -6- sulphur acetyl group -1-O- (6- nitrine hexyl)-β-D- glucopyranoside
At 2,3,4- tri--O- benzoyl -6-O- p-toluenesulfonyl -1-O- (6- nitrine hexyl)-β-D- glucopyranosides are molten
It reacts to obtain tri--O- benzoyl -6- sulphur acetyl of 2,3,4- in 65 DEG C with thioacetic acid potassium and tetrabutylammonium iodide in acetone
Base -1-O- (6- nitrine hexyl)-β-D- glucopyranoside；
The synthesis of (6) 1,8- bis--O- propargyls-anthraquinone, is dissolved in n,N-Dimethylformamide and carbonic acid for 1,8- dihydroxy anthraquinone
Potassium and bromo- 1 propine of 3- obtain bis--O- propargyl of 1,8--anthraquinone in room temperature reaction；
(7) synthesis of the anthraquinone glycoconjugate with protecting group, by 2,3,4- tri--O- benzoyl -6- sulphur acetyl group -1-O-
(6- nitrine hexyl)-β-D- glucopyranoside and bis--O- propargyl of 1,8--anthraquinone are dissolved in SODIUM ASCORBATE and five water sulfuric acid
Reaction obtains the anthraquinone glycoconjugate with protecting group under the conditions of being protected from light under the action of copper in 55 DEG C；
(8) synthesis of the anthraquinone glycoconjugate with cyclic structure, by the anthraquinone glycoconjugate with protecting group through being deprotected
To target product have cyclic structure anthraquinone glycoconjugate, wherein protecting group be acetyl or benzoyl base, deacetylation or
The condition of benzoyl is under the action of sodium methoxide, potassium carbonate, triethylamine or sodium hydroxide；
Reaction equation are as follows:
Wherein R3For Bz, n=4.
4. application of the anthraquinone glycoconjugate according to claim 1 with cyclic structure in environment measuring, feature
Be: the anthraquinone glycoconjugate with cyclic structure is used for as fluorescence probe in neutral DMF-H2Realization pair in O system
Cr3+Quantitative detection.
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| Anthraquinonyl glycoside facilitates the standardization of graphene electrodes for the impedance detection of lectins;Bi-Wen Zhu et al.;《Chemistry Central Journal》;20141125;第8卷;第1-6页 * |
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