CN102627267A - Fullerene polysaccharide derivative and its preparation method - Google Patents
Fullerene polysaccharide derivative and its preparation method Download PDFInfo
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- CN102627267A CN102627267A CN201210077694XA CN201210077694A CN102627267A CN 102627267 A CN102627267 A CN 102627267A CN 201210077694X A CN201210077694X A CN 201210077694XA CN 201210077694 A CN201210077694 A CN 201210077694A CN 102627267 A CN102627267 A CN 102627267A
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- soccerballene
- fullerene
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Abstract
The invention provides a fullerene polysaccharide derivative and its preparation method. The method comprises: adding 2-azidoethyl-2, 3, 4, 6-tetra-O-acetyl-beta-D-glucopyranoside and fullerene in a mole ratio of 1:1, dissolving them with chlorobenzene, conducting shading stirring for 12h at a temperature of 140DEG C and under inert gas protection; carrying out reduced pressure distillation so as to obtain tawny powder; dissolving the obtained tawny powder in a mixed solvent of chloroform and methanol that are in a ratio of 1:1, adding sodium methoxide until the pH reaches 9, and performing stirring for 30min under a temperature of 60DEG C; implementing neutralization with 25% acetic acid, then standing the mixture under refrigeration; and conducting filtration, then carrying out washing with methanol as well as vacuum drying, thus obtain the fullerene polysaccharide derivative. With fullerene and glucose as raw materials, the method of the invention synthesizes the fullerene polysaccharide derivative with nontoxicity to human bodies and good biological compatibility. The unique cancer cell-killing capability of the derivative can substantially improve the medical treatment level of mankind in treating bladder cancers.
Description
Technical field
What the present invention relates to is a kind of organic polymer material.The present invention also relates to a kind of preparation method of organic polymer material.Specifically be a kind of novel soccerballene polysaccharide derivates and preparation method.
Background technology
Soccerballene is the 4th kind of crystal habit of finding in 1985 of carbon after diamond, graphite and Linear Carbon (carbyne).It has good machinery, light, electricity, chemical property, is one of a kind of type material that receives much concern, and its performance has obtained using widely at Aeronautics and Astronautics, electron device, chemical field.In addition; The researchist finds that it also has some functions of medicine; Virus drugs scholar Si Xin Nagy (R.F.Schinazi) and his colleagues like medical college of U.S. Atlanta Ai Moli (Emory) university find; Fullerene ball has lethal effect to a kind of critical HIV (AIDS) viral enzyme, does not give birth to cell and do not injure the place.Though at present fullerene ball can't be as a kind of useful medicine, this will be a fullerene ball in biologically first Application; And scientist thinks that soccerballene will provide potential and interesting clue for the research cancer therapy drug.And discover that soccerballene under certain wavelength laser irradiation, can produce the effectively singlet oxygen of kill cancer cell.
Cancer is as the first healthy killer of harm humans, and the mankind's life has been brought maximum threat.In order to improve people's health level, effectively treating some malignant tumours is that people expect.Wherein, bladder cancer is as a kind of disease of internal organs canceration, and annual all have people up to ten thousand to lose one's life because of the diffusion of bladder cancer.The early treatment of bladder cancer can thousands of people's life offers an opportunity in order to save in the world.Minimum to the human injury when laser therapy is considered to treat cancer, a kind of therapy that efficient is higher is used very extensive recently clinically.The medicine that is used at present the laser therapy method abroad has photofrin (Photofrin), talaporfin sodium (Laserphyrin; Talaporfin Na) etc.; They can produce singlet oxygen under laser radiation, kill cancer cell is effectively treated and alleviated malignant tumours such as esophagus cancer, intestinal cancer.But their ubiquities are not high to the internal organs selectivity, in vivo the residence time long, to the spinoff of human body skin, only be applicable to the destruction of surperficial cancer cells, problems such as darkroom life for a long time.
For photosensitive medicine is combined with cancer cells effectively; Its medicine reaches the purpose of treatment cancer, even if should possess 1, good water-solubility 2, the purpose internal organs are had good selectivity 3, in human body, have the big condition that dosage also has no side effect to human body or spinoff is slight of certain residence time 4.And bladder is had good selectivity and under laser irradiation condition, can produce the principle of singlet oxygen according to soccerballene; The researchist also once prepared the fullerene derivate (as: polyoxyethylene deriv of soccerballene of treating bladder cancer; Polyethylenglycol); But their relatively poor or some other spinoffs because of biocompatibility mostly also do not reach the ideal effect till now, and cause influencing the popularization of soccerballene drug derivative.
Summary of the invention
The object of the present invention is to provide that a kind of not only to have had good biocompatibility but also had what under laser irradiation condition, produce singlet oxygen be the soccerballene polysaccharide derivates of tie point with the nitrogen-atoms.The present invention also aims to provide the preparation method of soccerballene polysaccharide derivates.
The objective of the invention is to realize like this:
Soccerballene carbohydrate derivative of the present invention has following structure:
Soccerballene carbohydrate derivative of the present invention prepares in such a way:
In the container that is provided with whisking appliance, prolong, TM, add 2-azidoethyl-2,3; 4,6-four-O-acetyl-β-D-glucopyranoside, soccerballene add 2-azidoethyl-2; 3,4, the mol ratio of 6-four-O-acetyl-β-D-glucopyranoside, soccerballene is 1: 1; It is dissolved in the chlorobenzene, and shading was stirred 12 hours under 140 ℃ (oil bath heating), argon shield condition.(developing solution: toluene/vinyl acetic monomer=2: 1), after the existence of affirmation resultant, underpressure distillation obtains crude product with TLC (ripple layer chromatography) tracking.After with developing solution unreacted soccerballene being separated, obtained dark brown powder 1.
The mixed solvent dissolving of products therefrom 1 usefulness chloroform/methanol=1/1 adds sodium methylate and reaches 9 until pH, stirs and continues and heated (60 ℃) 30 minutes.With in 25% acetic acid and after, be statically placed in the refrigerator.Filter with film filter, use methanol wash again, vacuum-drying gets product 2.
Soccerballene carbohydrate derivative molecular weight characterization of the present invention utilizes liquid chromatography-flight time mass spectrum combined instrument (U.S. 1200-6210 of Agilent company type), mass range m/z:50-12,000; Quality precision:＜2ppm, fastest sweep speed: 40spectra/s, resolving power (FWHM):＞13; 000, full scan sensitivity: column sample injection 10pg serpentine, s/n＞30: 1; Full scan sensitivity: analyze holoprotein, 20fmol, dynamicrange: 104; Interface: can connect capillary column, micro-column and common chromatographic column can connect capillary electrophoresis system; Chip liquid phase interface, data acquisition scheme: analog/digital conversion (ACD), environment is to the stability of mass axes:＜0.25ppm/ ℃.
Each component concentration test of soccerballene carbohydrate derivative of the present invention utilizes elemental analyser (the organic hydrocarbon nitrogen oxygen sulphur analyser of U.S. CE-440 type), operator scheme: CHN, CNS; N, S, O; Measurement range: C:0.002-50mg abs. (or100%), H:0.001-30mg abs. (or 100%), N:0.001-10mg abs. (or 100%); S:0.003-50mg abs. (or100%); Standard deviation :≤0.1%, sample is claimed appearance: 0.001～500mg, sampler: 64 full-automatic samplers.
The photosensitivity of soccerballene the carbohydrate derivative of the present invention and chromosomal heteroploidy of human body cell toxicity, tumour cell measured utilize flow cytometer (U.S. company BD FACSCalibur) detects.
Soccerballene carbohydrate derivative of the present invention and bladder have good selectivity, to human non-toxic, and under laser irradiation condition, can produce singlet oxygen, Gu have very high expected value aspect effective treatment of bladder cancer.
The present invention is a raw material with soccerballene, glucose, has synthesized human non-toxic property, the good soccerballene carbohydrate derivative of biocompatibility, and the ability of the kill cancer cell that it is unique is with the medical level that improves human treatment's bladder cancer greatly.
Embodiment
For example the present invention is done more detailed description below:
1,2,3,4,6-five-O-ethanoyl-β-D-glucose synthetic
(25.2g, 0.307mol) the middle 350ml Glacial acetic acid that adds is heated to 140 ℃, under system ebullient condition, adds 50.0gD-glucose slowly toward sodium acetate, anhydrous.After adding finishes, continue to be heated to boiling, finish, place the room temperature cooling until reaction.Reaction solution is injected into 1 liter above the ice cube, after stirring 4 hours, generates dark brown deposition.Wash to not having acetic acid flavor, drying under reduced pressure with sleeping behind the suction filtration.The material that obtains adds 400mL ethanol, and heating while stirring makes its dissolving.After the adding gac fully stirred, suction filtration was removed gac while hot.The solution that obtains continues heating, and naturally cooling after evaporating solvent to the general quantity is put at last to refrigerator and made its crystallization.Behind the crystallization suction filtration that obtains, with the small amount of ethanol washing, drying under reduced pressure obtains white solid (67.8g).
2-bromotrifluoromethane 2,3,4,6-four-O-ethanoyl-β-D-glucose synthetic
With 1,2,3,4; (9.48g 24.8mmol) is dissolved in the 100mL methylene dichloride 6-five-O-ethanoyl-β-D-glucose, adds two-bromoethanol (3.10g; 24.8mmol), under argon shield, in ice bath, slowly drip boron trifluoride ethyl ether complex (BF while stirring
3OEt
2, 10mL 79.3mmol), continues in ice bath, to stir after one hour the room temperature shading and stirred 12 hours.With the organic layer that obtains in order to water, saturated NaHCO
3The order washing of the aqueous solution, the saturated NaCl aqueous solution.Use anhydrous Na
2SO
4After removing moisture, obtain yellow oily resultant (10.2g) through filtration, underpressure distillation.
2-azidoethyl 2,3,4,6-four-O-ethanoyl-β-D-glucose synthetic
With 2-bromotrifluoromethane 2,3,4,6-four-O-ethanoyl-β-D-glucose (2.5g, 5.49mmol) be dissolved in N (DMF, 30mL) in, under condition of ice bath, add sodium azide (NaN3,3.57g, 54.8mmol) after, under 80 ℃ of heating conditions, stirred 12 hours.With reaction solution with ethyl acetate extraction after, in order to water, saturated NaHCO
3The order washing of the aqueous solution, the saturated NaCl aqueous solution.Use anhydrous Na
2SO
4After removing moisture, obtain the yellow oily resultant through filtration, underpressure distillation.It being dissolved in a spot of methylene dichloride, is that poor solvent carries out recrystallization with ethanol again, obtains lurid crystallization (0.941g).
With the nitrogen-atoms soccerballene glucose-derivative synthetic of tie point
In the container that is provided with whisking appliance, prolong, TM, add 2-azidoethyl-2,3; 4,6-four-O-acetyl-β-D-glucopyranoside, soccerballene add 2-azidoethyl-2; 3,4, the mol ratio of 6-four-O-acetyl-β-D-glucopyranoside, soccerballene is 1: 1; It is dissolved in the 100ml chlorobenzene, and shading was stirred 12 hours under 140 ℃ (oil bath heating), argon shield condition.(developing solution: toluene/vinyl acetic monomer=2: 1), after the existence of affirmation resultant, underpressure distillation obtains crude product with TLC (ripple layer chromatography) tracking.After with developing solution unreacted soccerballene being separated, obtained dark brown powder 1.ESI-TOF?MS(m/z)＝[M+Na]
+calcd.for?C
76H
23O
10N，1132.12；found，1132.01.Anal.Calcd.for?C
76H
23O
10N:C，82.24；H，2.09；N，1.26.Found:C，82.26；H，2.36；N，0.94
The mixed solvent dissolving of the dark brown powder of products therefrom 1 usefulness chloroform/methanol=1/1 adds sodium methylate and reaches 9 until pH, stirs and continues and heated (60 ℃) 30 minutes.With in 25% acetic acid and after, be statically placed in the refrigerator.Filter with film filter, use methanol wash again, vacuum-drying gets product 2.
Product 2 is carried out the examination of infrared spectrum result can be found out, removes in the IR spectrum behind the ethanoyl not observe original ester group stretching vibration peak, the substitute is the absorption peak of hydroxyl origin, and what can confirm to obtain is purpose product 2.IR(KBr，cm
-1)：3429，2978，1645，1472，1024，527。
Claims (3)
1. soccerballene carbohydrate derivative is characterized in that having following structure:
2. the preparation method of a soccerballene carbohydrate derivative is characterized in that:
1) in container, add mol ratio and be 1: 1 2-azidoethyl-2,3,4,6-four-O-acetyl-β-D-glucopyranoside and soccerballene will dissolve with chlorobenzene, and the shading stirring is 12 hours under 140 ℃, protection of inert gas condition; Underpressure distillation obtains dark brown powder;
2) the dark brown powder of gained is used chloroform: the mixed solvent dissolving of methyl alcohol=1: 1 adds sodium methylate and reaches under 9,60 ℃ of temperature until pH and stirred 30 minutes; With in 25% acetic acid and after, be statically placed in refrigeration; Filter, use methanol wash again, vacuum-drying obtains the soccerballene polysaccharide derivates.
3. the preparation method of soccerballene polysaccharide derivates according to claim 2 is characterized in that: said rare gas element is an argon gas.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104877034A (en) * | 2015-05-08 | 2015-09-02 | 长春理工大学 | Fullerene cellulose derivative used as chiral stationary phase material and preparation method of fullerene cellulose derivative |
| CN107551272A (en) * | 2017-10-18 | 2018-01-09 | 北京福纳康生物技术有限公司 | N fullerene aminoacid derivates nano particle is preparing the application of illumination condition medicaments for treating tumors under and medicine |
| CN107602647A (en) * | 2017-09-04 | 2018-01-19 | 深圳市聚华太科技有限公司 | A kind of full acetylated glucosan derivative of C70 fullerenes and its application as anode material of lithium battery |
| CN107602646A (en) * | 2017-09-04 | 2018-01-19 | 深圳市聚华太科技有限公司 | A kind of full acetylated glucosan derivative of C60 fullerenes and its application as anode material of lithium battery |
| CN114773411A (en) * | 2022-05-09 | 2022-07-22 | 内蒙古大学 | Synthesis method of lactose fullerene antitumor lead compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6844429B2 (en) * | 2001-01-19 | 2005-01-18 | San-Ei Gen F.F.I. | Fullerene derivative and composition comprising the same |
-
2012
- 2012-03-22 CN CN201210077694XA patent/CN102627267A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6844429B2 (en) * | 2001-01-19 | 2005-01-18 | San-Ei Gen F.F.I. | Fullerene derivative and composition comprising the same |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104877034A (en) * | 2015-05-08 | 2015-09-02 | 长春理工大学 | Fullerene cellulose derivative used as chiral stationary phase material and preparation method of fullerene cellulose derivative |
| CN104877034B (en) * | 2015-05-08 | 2017-04-05 | 长春理工大学 | Fullerene fiber as chiral stationary phase material element derivant and preparation method thereof |
| CN107602647A (en) * | 2017-09-04 | 2018-01-19 | 深圳市聚华太科技有限公司 | A kind of full acetylated glucosan derivative of C70 fullerenes and its application as anode material of lithium battery |
| CN107602646A (en) * | 2017-09-04 | 2018-01-19 | 深圳市聚华太科技有限公司 | A kind of full acetylated glucosan derivative of C60 fullerenes and its application as anode material of lithium battery |
| CN107551272A (en) * | 2017-10-18 | 2018-01-09 | 北京福纳康生物技术有限公司 | N fullerene aminoacid derivates nano particle is preparing the application of illumination condition medicaments for treating tumors under and medicine |
| CN114773411A (en) * | 2022-05-09 | 2022-07-22 | 内蒙古大学 | Synthesis method of lactose fullerene antitumor lead compound |
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Application publication date: 20120808 |