CN102746346B - Fullerene monosaccharide derivative using carbon atoms as connection points and preparation method thereof - Google Patents
Fullerene monosaccharide derivative using carbon atoms as connection points and preparation method thereof Download PDFInfo
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- CN102746346B CN102746346B CN201210224689.7A CN201210224689A CN102746346B CN 102746346 B CN102746346 B CN 102746346B CN 201210224689 A CN201210224689 A CN 201210224689A CN 102746346 B CN102746346 B CN 102746346B
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- glucose
- soccerballene
- fullerene
- acetyl
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- -1 Fullerene monosaccharide derivative Chemical class 0.000 title claims abstract description 27
- 229910003472 fullerene Inorganic materials 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 125000004432 carbon atom Chemical group C* 0.000 title abstract 3
- 238000003756 stirring Methods 0.000 claims abstract description 34
- XMWRBQBLMFGWIX-UHFFFAOYSA-N C60 fullerene Chemical compound C12=C3C(C4=C56)=C7C8=C5C5=C9C%10=C6C6=C4C1=C1C4=C6C6=C%10C%10=C9C9=C%11C5=C8C5=C8C7=C3C3=C7C2=C1C1=C2C4=C6C4=C%10C6=C9C9=C%11C5=C5C8=C3C3=C7C1=C1C2=C4C6=C2C9=C5C3=C12 XMWRBQBLMFGWIX-UHFFFAOYSA-N 0.000 claims abstract description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 22
- HXBYBCASAVUYKF-GVYWOMJSSA-N (4r,5s,6r,7r)-4,5,6,7,8-pentahydroxyoctane-2,3-dione Chemical compound CC(=O)C(=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO HXBYBCASAVUYKF-GVYWOMJSSA-N 0.000 claims abstract description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000010438 heat treatment Methods 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 239000012046 mixed solvent Substances 0.000 claims abstract description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 14
- 150000001721 carbon Chemical group 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 10
- 239000012346 acetyl chloride Substances 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 229960000583 acetic acid Drugs 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 238000004821 distillation Methods 0.000 claims description 7
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 6
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- 238000002425 crystallisation Methods 0.000 claims description 6
- 230000008025 crystallization Effects 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 238000000967 suction filtration Methods 0.000 claims description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 238000009835 boiling Methods 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 238000010926 purge Methods 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- QWRMAKBIFINJGH-UHFFFAOYSA-N CCCC.BrCC(=O)O Chemical compound CCCC.BrCC(=O)O QWRMAKBIFINJGH-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- DPAXDKFCBLGMIZ-IBEHDNSVSA-N [(2r,3r,4s,5r,6r)-3,4,5-triacetyloxy-6-(2-azidoethoxy)oxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@H]1O[C@@H](OCCN=[N+]=[N-])[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O DPAXDKFCBLGMIZ-IBEHDNSVSA-N 0.000 claims description 3
- IEOLRPPTIGNUNP-RKQHYHRCSA-N [(2r,3r,4s,5r,6r)-3,4,5-triacetyloxy-6-hydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@H]1O[C@@H](O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O IEOLRPPTIGNUNP-RKQHYHRCSA-N 0.000 claims description 3
- 230000005587 bubbling Effects 0.000 claims description 3
- 239000012230 colorless oil Substances 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 238000006386 neutralization reaction Methods 0.000 claims description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical class [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- BMFFEYWVZKHJPO-IBEHDNSVSA-N [(2R,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(2-azidoethyl)-6-hydroxyoxan-2-yl]methyl acetate Chemical compound N(=[N+]=[N-])CC[C@]1(O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H](O1)COC(C)=O BMFFEYWVZKHJPO-IBEHDNSVSA-N 0.000 claims description 2
- 229940040526 anhydrous sodium acetate Drugs 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 239000012362 glacial acetic acid Substances 0.000 claims description 2
- 239000012044 organic layer Substances 0.000 claims description 2
- 238000001556 precipitation Methods 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- 206010005003 Bladder cancer Diseases 0.000 abstract description 7
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 abstract description 7
- 201000005112 urinary bladder cancer Diseases 0.000 abstract description 7
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 abstract 1
- AITBHTAFQQYBHP-UHFFFAOYSA-N benzene;pyridine Chemical compound C1=CC=CC=C1.C1=CC=NC=C1 AITBHTAFQQYBHP-UHFFFAOYSA-N 0.000 abstract 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 abstract 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 abstract 1
- 229960002442 glucosamine Drugs 0.000 abstract 1
- 230000003472 neutralizing effect Effects 0.000 abstract 1
- 231100000956 nontoxicity Toxicity 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- VSEIDZLLWQQJGK-CHOZPQDDSA-N CCC1=C(C)C2=N\C\1=C/C1=C(C)C(C(O)=O)=C(N1)\C(CC(=O)N[C@@H](CC(O)=O)C(O)=O)=C1/N=C(/C=C3\N/C(=C\2)C(C=C)=C3C)[C@@H](C)[C@@H]1CCC(O)=O Chemical compound CCC1=C(C)C2=N\C\1=C/C1=C(C)C(C(O)=O)=C(N1)\C(CC(=O)N[C@@H](CC(O)=O)C(O)=O)=C1/N=C(/C=C3\N/C(=C\2)C(C=C)=C3C)[C@@H](C)[C@@H]1CCC(O)=O VSEIDZLLWQQJGK-CHOZPQDDSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 229950010924 talaporfin Drugs 0.000 description 3
- 210000001835 viscera Anatomy 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 2
- 238000002647 laser therapy Methods 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229920000620 organic polymer Polymers 0.000 description 2
- 229940109328 photofrin Drugs 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 206010034972 Photosensitivity reaction Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- LOTCVJJDZFMQGB-UHFFFAOYSA-N [N].[O].[S] Chemical compound [N].[O].[S] LOTCVJJDZFMQGB-UHFFFAOYSA-N 0.000 description 1
- WYTGDNHDOZPMIW-RCBQFDQVSA-N alstonine Natural products C1=CC2=C3C=CC=CC3=NC2=C2N1C[C@H]1[C@H](C)OC=C(C(=O)OC)[C@H]1C2 WYTGDNHDOZPMIW-RCBQFDQVSA-N 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003118 drug derivative Substances 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- VRLIPUYDFBXWCH-UHFFFAOYSA-N hydridocarbon(.) Chemical compound [CH] VRLIPUYDFBXWCH-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000005501 phase interface Effects 0.000 description 1
- 230000036211 photosensitivity Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000010801 sewage sludge Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
Abstract
The invention provides a fullerene monosaccharide derivative using carbon atoms as connection points and a preparation method thereof. The method comprises steps of: dissolving fullerene acetyl chloride derivative and acetylated glucosamine ethyl hydrochloride in a molar ratio of 1:1 in pyridine benzene; stirring for 12 hours while heating at 60 DEG C to obtain fullerene acetyl glucose; drying in vacuum and dissolving in a mixed solvent containing methanol and chloroform in a ratio of 1:1; adding sodium methoxide and stirring for 30 minutes; neutralizing by acetic acid; and removing the solvent to obtain the fullerene monosaccharide derivative using carbon atoms as connection points. The fullerene monosaccharide derivative provided by the invention has good selectivity on bladder and no toxicity to human, and can efficiently generate singlet oxygenin under laser irradiation; therefore, the fullerene monosaccharide derivative has high expectations in effective treatment of bladder cancer.
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 a kind of take carbon atom as soccerballene monosaccharide derivatives and the preparation method of tie point.
Background technology
Soccerballene is the 4th kind of crystal habit of carbon after diamond, graphite and Linear Carbon (carbyne) found in 1985.It has excellent machinery, optical, electrical, chemical property, and be one of a kind of type material received much concern, its performance is widely used at Aeronautics and Astronautics, electron device, chemical field.In addition, researchist finds that it also has some functions of medicine, as virus drugs scholar Si Xin Nagy (R.F.Schinazi) of U.S.'s Atlanta Ai Moli (Emory) University Medical College and his colleagues find, fullerene ball is to the critical HIV(acquired immune deficiency syndrome (AIDS) of one) viral enzyme has lethal effect, and do not injure the raw cell in place.Although fullerene ball can't as a kind of useful medicine at present, this will be that fullerene ball is in first Application biologically; And scientist thinks, soccerballene provides potential and interesting clue by for Effect of Anti cancer drug.And research finds that soccerballene is under certain wavelength laser irradiates, and can produce the singlet oxygen that effectively can kill cancer cells.
Cancer, as the first killer of harm humans health, brings maximum threat to the life of the mankind.In order to improve the health level of people, effectively some malignant tumours for the treatment of are that people expected.Wherein, bladder cancer, as a kind of disease of internal organs canceration, has people up to ten thousand to lose one's life because of the diffusion of bladder cancer every year.The early treatment of bladder cancer, can offer an opportunity for the life saving thousands of people in the world.Minimum to human injury when laser therapy is considered to Therapeutic cancer, a kind of therapy that efficiency is higher, applies widely recently clinically.Photofrin (Photofrin), Talaporfin Sodium (Laserphyrin is had abroad at present for the medicine of laser therapy method, Talaporfin Na) etc., they can produce singlet oxygen under laser radiation, kill cancer cells, effectively treat and alleviate the malignant tumour such as esophagus cancer, intestinal cancer.But their ubiquities are not high to internal organs selectivity, in vivo the residence time long, to the side effect of human body skin, the problem such as destruction, for a long time darkroom life being only applicable to surperficial cancer cells.
In order to photosensitive medicine can be made effectively to combine with cancer cells, reach the object of Therapeutic cancer, its medicine should possess: 1, good water-soluble; 2, to object internal organs, there is good selectivity; 3, there is certain residence time in human body; Even if the condition that 4 larger dosages also have no side effect to human body or side effect is slight.And to bladder, there is good selectivity according to soccerballene and the principle of singlet oxygen can be produced under laser irradiation condition, researchist also once prepared the fullerene derivate (as: polyoxyethylene deriv of soccerballene for the treatment of bladder cancer, Polyethylenglycol), but they are mostly because biocompatibility is poor or have some other side effects, also do not reach desirable effect till now, and cause affecting the popularization of soccerballene drug derivative and the result for the treatment of for some cancer.
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 take carbon atom as the soccerballene monosaccharide derivatives of tie point.The present invention also aims to provide a kind of richness to take carbon atom as the preparation method of the soccerballene monosaccharide derivatives of tie point.
The object of the present invention is achieved like this:
Of the present invention is that the soccerballene monosaccharide derivatives of tie point has following structure with carbon atom:
Of the present invention to take carbon atom as the preparation method of the soccerballene monosaccharide derivatives of tie point be: be dissolved in pyridine by soccerballene Acetyl Chloride 98Min. derivative, acetyl glucose aminoethyl hydrochloride; stir 12 hours under 60 DEG C of heating conditions; obtain soccerballene acetyl glucose; after vacuum-drying; be dissolved in the mixed solvent of methyl alcohol/chloroform=1:1; adding after sodium methylate stirs 30 minutes, with acetic acid neutralization, take carbon atom as the soccerballene monosaccharide derivatives of tie point except obtaining rich after desolventizing.
Of the present invention is that the preparation method of the soccerballene monosaccharide derivatives of tie point can also comprise with carbon atom:
1, described soccerballene Acetyl Chloride 98Min. derivative is adopted and is prepared with the following method: be dissolved in acetone by bromoacetic acid butane and dimethyl thioether, stirs 24 hours at ambient temperature, filters rear washing with acetone, obtain Me
2sCO
2 tbu Bromide white powder; By Me
2sCO
2 tbu Bromide is dissolved in methylene dichloride, and while stirring under condition of ice bath, dropping unsaturated carbonate potassium solution and volume by volume concentration are the NaOH solution of 50%, stir 10 minutes, continues to stir 20 minutes at room temperature, adds CaH after being removed by clear liquor
2, until not bubbling, dry, cross and filter to remove CaH
2, after underpressure distillation, obtain Me
2sCO
2 tbu salt colorless oil;
By Dissolving fullerene in methane, respectively with Me
2sCO
2 tbu salt, trifluoroacetic acid, thionyl chloride are reacted, and obtain the dark brown powder of soccerballene Acetyl Chloride 98Min. derivative.
2, described acetyl glucose aminoethyl hydrochloride is adopted and is prepared with the following method: in the container being provided with agitator, prolong, thermometer, adds 2-azidoethyl-2,3,4,6-tetra--O-acetyl-β-D-glucopyranoside, chloroform, PtO
2, pass into hydrogen at ambient temperature 3 days, filter PtO
2, obtain acetyl glucose aminoethyl hydrochloride salt as white powder.
Soccerballene monosaccharide derivatives molecular weight characterization of the present invention utilizes sewage sludge combined instrument (U.S. Agilent company 1200-6210 type), mass range m/z:50-12,000, Mass accuracy: <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: 10
4, 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/ DEG C.
The test of soccerballene monosaccharide derivatives of the present invention each component concentration utilizes elemental analyser (the organic hydrocarbon nitrogen oxygen sulphur content analyzer of U.S. CE-440 type), operator scheme: CHN, CNS, N, S, O, measurement range: C:0.002-50mg abs. (or 100%), 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 samples: 0.001 ~ 500mg, sampler: 64 full-automatic samplers.
The photosensitivity of soccerballene monosaccharide derivatives of the present invention and human body cell toxicity, the chromosomal heteroploidy of tumour cell are measured and utilize flow cytometer (U.S. company BD, FACSCalibur) to detect.
Soccerballene carbohydrate derivative of the present invention and bladder have good selectivity, to human non-toxic, and can high efficiency generation singlet oxygen under laser irradiation condition, Gu there is very high expected value in effective treatment of bladder cancer.
The present invention is with soccerballene, glucose for raw material, and synthesized human non-toxic's property, the good soccerballene monosaccharide derivatives of biocompatibility, the ability of killing cancer cells of its uniqueness, will improve the medical level of human treatment's bladder cancer greatly.
Embodiment
Soccerballene monosaccharide derivatives of the present invention is prepared in such a way:
1, the preparation of soccerballene Acetyl Chloride 98Min. derivative:
1) bromoacetic acid butane (19.5g, 0.10mol) and dimethyl thioether (6.21g, 0.10mol) are dissolved in 50mL acetone, stir 24 hours at ambient temperature.Filter rear washing with acetone, obtain Me
2sCO
2 tbu Bromide (white powder (16.8g, 0.095mol); By Me
2sCO
2 tbu Bromide (100mg, 0.56mmol) is dissolved in 5mL methylene dichloride, while stirring, drips unsaturated carbonate potassium solution 0.34mL and 50%NaOH solution 25 μ L, stirs 10 minutes under condition of ice bath, continues to stir 20 minutes at room temperature.CaH is added after being removed by clear liquor
2, until not bubbling, dry, filter this system, remove CaH
2, after underpressure distillation, obtain Me
2sCO
2 tbu salt colorless oil (180mg).
This reaction process can represent with following formula:
2) by Dissolving fullerene in methane, respectively with Me
2sCO
2 tbu salt, trifluoroacetic acid, thionyl chloride are reacted, and obtain the dark brown powder of soccerballene Acetyl Chloride 98Min. derivative ([60] fullerene acetyl chloride).
This reaction process can represent with following formula:
2, the preparation of acetyl glucose aminoethyl hydrochloride:
1) synthesis of 1,2,3,4,6-five-O-ethanoyl-β-D-Glucose
In sodium acetate, anhydrous (25.2g, 0.307mol), add 350ml Glacial acetic acid, be heated to 140 DEG C, under the condition of boiling, slowly add 50.0gD-glucose.After adding, continue to be heated to boiling, until reaction terminates, place room temperature cooling.Reaction solution is injected into above 1 liter of ice cube, generates dark brown precipitation after 4 hours in stirring.Rinse to there is no acetic acid taste, drying under reduced pressure with water after suction filtration.The material obtained adds 400mL ethanol, heats while stirring and makes it dissolve.Add after gac fully stirs, suction filtration while hot, removing gac.The solution that obtains continues heating, naturally cooling after evaporating solvent to general quantity, finally puts to refrigerator and makes its crystallization.By after the crystallization suction filtration that obtains, use a small amount of washing with alcohol, drying under reduced pressure, obtain white solid (67.8g).
2) synthesis of 2-bromotrifluoromethane 2,3,4,6-tetra--O-ethanoyl-β-D-Glucose
By 1,2,3; 4; 6-five-O-ethanoyl-β-D-Glucose (9.48g, 24.8mmol) is dissolved in 100mL methylene dichloride, adds two-bromoethanol (3.10g; 24.8mmol); under argon shield, in ice bath, slowly drip boron trifluoride ethyl ether complex (BF3OEt2,10mL while stirring; 79.3mmol), continue in ice bath, stir room temperature shading after a hour and stir 12 hours.By the organic layer that obtains in order to water, saturated NaHCO
3the sequential purge of the aqueous solution, the saturated NaCl aqueous solution.Use anhydrous Na
2sO
4after removing moisture, after filtration, underpressure distillation obtains yellow oily resultant (10.2g).
3) synthesis of 2-azidoethyl 2,3,4,6-tetra--O-ethanoyl-β-D-Glucose
By 2-bromotrifluoromethane 2,3,4,6-tetra--O-ethanoyl-β-D-Glucose (2.5g; 5.49mmol) be dissolved in dimethyl formamide (DMF, 30mL), under condition of ice bath, add sodium azide (NaN3; 3.57g, 54.8mmol) after, stir 12 hours under 80 DEG C of heating conditions.After reaction solution is extracted with ethyl acetate, in order to water, saturated NaHCO
3the sequential purge of the aqueous solution, the saturated NaCl aqueous solution.Use anhydrous Na
2sO
4after removing moisture, after filtration, underpressure distillation obtains yellow oily resultant.Be dissolved in a small amount of methylene dichloride again, be that poor solvent carries out recrystallization with ethanol, obtain lurid crystallization (0.941g).
4) acetyl glucose aminoethyl hydrochloride
To in the container being provided with agitator, prolong, thermometer, add 2-azidoethyl-2,3,4,6-tetra--O-acetyl-β-D-glucopyranoside, chloroform, PtO
2, pass into hydrogen at ambient temperature 3 days, filter PtO
2, obtain acetyl glucose aminoethyl hydrochloride salt as white powder.
The preparation of acetyl glucose aminoethyl hydrochloride can represent with following formula:
3, take carbon atom as the synthesis of soccerballene monosaccharide derivatives of tie point
The soccerballene Acetyl Chloride 98Min. derivative obtained, acetyl glucose aminoethyl hydrochloride are dissolved in pyridine; stir 12 hours under 60 DEG C of heating conditions; obtain soccerballene acetyl glucose; after vacuum-drying; be dissolved in the mixed solvent of methyl alcohol/chloroform=1:1; add after sodium methylate stirs 30 minutes, with acetic acid neutralization, except obtaining soccerballene monosaccharide derivatives after desolventizing.
This reaction process can represent with following formula:
Claims (3)
1. one kind take carbon atom as the preparation method of the soccerballene monosaccharide derivatives of tie point; it is characterized in that: be that soccerballene Acetyl Chloride 98Min. derivative, the acetyl glucose aminoethyl hydrochloride of 1:1 is dissolved in pyridine by mol ratio; stir 12 hours under 60 DEG C of heating conditions; obtain soccerballene acetyl glucose; after vacuum-drying; be dissolved in the mixed solvent of methyl alcohol/chloroform=1:1; add after sodium methylate stirs 30 minutes; with acetic acid neutralization, except obtaining taking carbon atom as the soccerballene monosaccharide derivatives of tie point after desolventizing.
2. according to claim 1 take carbon atom as the preparation method of the soccerballene monosaccharide derivatives of tie point, it is characterized in that described soccerballene Acetyl Chloride 98Min. derivative is adopted to prepare with the following method: bromoacetic acid butane and dimethyl thioether are dissolved in acetone, stir 24 hours at ambient temperature, filter rear washing with acetone, obtain Me
2sCO
2 tbu Bromide white powder; By Me
2sCO
2 tbu Bromide is dissolved in methylene dichloride, and while stirring under condition of ice bath, dropping unsaturated carbonate potassium solution and volume by volume concentration are the NaOH solution of 50%, stir 10 minutes, continues to stir 20 minutes at room temperature, adds CaH after being removed by clear liquor
2, until not bubbling, dry, cross and filter to remove CaH
2, after underpressure distillation, obtain Me
2sCO
2 tbu salt colorless oil;
By Dissolving fullerene in toluene, respectively with Me
2sCO
2 tbu salt, trifluoroacetic acid, thionyl chloride are reacted, and obtain the dark brown powder of soccerballene Acetyl Chloride 98Min. derivative.
3. according to claim 1 and 2 take carbon atom as the preparation method of the soccerballene monosaccharide derivatives of tie point, it is characterized in that described acetyl glucose aminoethyl hydrochloride is adopted and prepares with the following method:
1) synthesis of 1,2,3,4,6-five-O-ethanoyl-β-D-Glucose
Toward 25.2g, 350ml Glacial acetic acid is added in 0.307mol sodium acetate, anhydrous, be heated to 140 DEG C, under the condition of boiling, slowly 50.0gD-glucose is added, after adding, continue to be heated to boiling, until reaction terminates, placement room temperature cools, reaction solution is injected into above 1 liter of ice cube, dark brown precipitation is generated after 4 hours in stirring, rinse to there is no acetic acid taste with water after suction filtration, drying under reduced pressure, the material obtained adds 400mL ethanol, heat while stirring and make it dissolve, add after gac fully stirs, the solution that suction filtration obtains while hot continues heating, naturally cooling after evaporating solvent, finally put to refrigerator and make its crystallization, by after the crystallization suction filtration that obtains, use a small amount of washing with alcohol, drying under reduced pressure, obtain white solid,
2) synthesis of 2-bromotrifluoromethane 2,3,4,6-tetra--O-ethanoyl-β-D-Glucose
By 9.48g, 24.8mmol 1; 2; 3,4,6-five-O-ethanoyl-β-D-Glucose is dissolved in 100mL methylene dichloride; add 3.10g; 24.8mmol two-bromoethanol, under argon shield, in ice bath, slowly drip 10mL, 79.3mmol boron trifluoride ethyl ether complex while stirring; continue in ice bath, stir room temperature shading after a hour and stir 12 hours, by the organic layer that obtains in order to water, saturated NaHCO
3the sequential purge of the aqueous solution, the saturated NaCl aqueous solution, uses anhydrous Na
2sO
4after removing moisture, after filtration, underpressure distillation obtains yellow oily resultant;
3) synthesis of 2-azidoethyl 2,3,4,6-tetra--O-ethanoyl-β-D-Glucose
By 2.5g; 5.49mmol 2-bromotrifluoromethane 2; 3; 4; 6-tetra--O-ethanoyl-β-D-Glucose is dissolved in 30mL dimethyl formamide, after adding 3.57g, 54.8mmol sodium azide, stirs 12 hours under 80 DEG C of heating conditions under condition of ice bath; after reaction solution is extracted with ethyl acetate, in order to water, saturated NaHCO
3the sequential purge of the aqueous solution, the saturated NaCl aqueous solution, uses anhydrous Na
2sO
4after removing moisture, after filtration, underpressure distillation obtains yellow oily resultant, then is dissolved in methylene dichloride, is that poor solvent carries out recrystallization, obtains lurid crystallization with ethanol;
4) acetyl glucose aminoethyl hydrochloride
To in the container being provided with agitator, prolong, thermometer, add 2-azidoethyl-2,3,4,6-tetra--O-acetyl-β-D-glucopyranoside, chloroform, PtO
2, pass into hydrogen at ambient temperature 3 days, filter PtO
2, obtain acetyl glucose aminoethyl hydrochloride salt as white powder.
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