CN105440062A - Synthesizing method of voriconazole copper acetate complex with anti-bacterial activity - Google Patents
Synthesizing method of voriconazole copper acetate complex with anti-bacterial activity Download PDFInfo
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- CN105440062A CN105440062A CN201610010387.8A CN201610010387A CN105440062A CN 105440062 A CN105440062 A CN 105440062A CN 201610010387 A CN201610010387 A CN 201610010387A CN 105440062 A CN105440062 A CN 105440062A
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- BCEHBSKCWLPMDN-MGPLVRAMSA-N voriconazole Chemical compound C1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=NC=C1F BCEHBSKCWLPMDN-MGPLVRAMSA-N 0.000 title claims abstract description 20
- 229960004740 voriconazole Drugs 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 title claims abstract description 8
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 6
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 title claims abstract 4
- 230000002194 synthesizing effect Effects 0.000 title abstract 4
- 239000003960 organic solvent Substances 0.000 claims abstract 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract 3
- 241001673062 Achromobacter xylosoxidans Species 0.000 claims abstract 2
- 241001225321 Aspergillus fumigatus Species 0.000 claims abstract 2
- 241000228245 Aspergillus niger Species 0.000 claims abstract 2
- 244000063299 Bacillus subtilis Species 0.000 claims abstract 2
- 241000222122 Candida albicans Species 0.000 claims abstract 2
- 201000007336 Cryptococcosis Diseases 0.000 claims abstract 2
- 241000221204 Cryptococcus neoformans Species 0.000 claims abstract 2
- 241000222126 [Candida] glabrata Species 0.000 claims abstract 2
- 229940091771 aspergillus fumigatus Drugs 0.000 claims abstract 2
- 239000000022 bacteriostatic agent Substances 0.000 claims abstract 2
- 229940095731 candida albicans Drugs 0.000 claims abstract 2
- 208000032343 candida glabrata infection Diseases 0.000 claims abstract 2
- 239000000126 substance Substances 0.000 claims abstract 2
- 230000015572 biosynthetic process Effects 0.000 claims description 19
- 238000003786 synthesis reaction Methods 0.000 claims description 19
- 230000000845 anti-microbial effect Effects 0.000 claims description 14
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 claims description 9
- 229910052751 metal Inorganic materials 0.000 claims description 8
- 239000002184 metal Substances 0.000 claims description 8
- 238000010189 synthetic method Methods 0.000 claims description 6
- -1 tetracol phenixin Chemical compound 0.000 claims description 4
- 230000003385 bacteriostatic effect Effects 0.000 claims description 3
- 230000004071 biological effect Effects 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 claims 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims 1
- 241000235645 Pichia kudriavzevii Species 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 229960001701 chloroform Drugs 0.000 claims 1
- 239000010949 copper Substances 0.000 claims 1
- 239000012046 mixed solvent Substances 0.000 claims 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims 1
- 239000003921 oil Substances 0.000 claims 1
- 239000013078 crystal Substances 0.000 abstract description 8
- 238000002474 experimental method Methods 0.000 abstract description 2
- 238000002329 infrared spectrum Methods 0.000 abstract 2
- 241000228197 Aspergillus flavus Species 0.000 abstract 1
- 241001465318 Aspergillus terreus Species 0.000 abstract 1
- 235000014469 Bacillus subtilis Nutrition 0.000 abstract 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 238000011160 research Methods 0.000 description 7
- 239000002262 Schiff base Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 150000003852 triazoles Chemical class 0.000 description 3
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 2
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 2
- YBRVSVVVWCFQMG-UHFFFAOYSA-N 4,4'-diaminodiphenylmethane Chemical compound C1=CC(N)=CC=C1CC1=CC=C(N)C=C1 YBRVSVVVWCFQMG-UHFFFAOYSA-N 0.000 description 2
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 2
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 2
- 238000003889 chemical engineering Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 description 1
- BLSQLHNBWJLIBQ-OZXSUGGESA-N (2R,4S)-terconazole Chemical compound C1CN(C(C)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2N=CN=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 BLSQLHNBWJLIBQ-OZXSUGGESA-N 0.000 description 1
- CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 description 1
- XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 description 1
- FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 description 1
- LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 description 1
- CAHGCLMLTWQZNJ-UHFFFAOYSA-N Nerifoliol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C CAHGCLMLTWQZNJ-UHFFFAOYSA-N 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- QBSJHOGDIUQWTH-UHFFFAOYSA-N dihydrolanosterol Natural products CC(C)CCCC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 QBSJHOGDIUQWTH-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229940089256 fungistat Drugs 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical compound C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 description 1
- 229940058690 lanosterol Drugs 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- JJVNINGBHGBWJH-UHFFFAOYSA-N ortho-vanillin Chemical compound COC1=CC=CC(C=O)=C1O JJVNINGBHGBWJH-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/08—Copper compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a synthesizing method of a voriconazole copper acetate complex with anti-bacterial activity. The synthesizing method comprises the following steps of dissolving voriconazole (FZ) and copper acetate into a certain amount of water and organic solvent; then, transferring a reaction mixture into a flask, heating, lowering the temperature to the room temperature, filtering, stilling, separating a deep blue blocky target product, and using single-crystal X-rays to determine a crystal structure (refer to figure 1). A chemical formula is [Cu2(FZ)2(CH3COO)2(H2O)].2H2O, and the complex is absorbed by ultraviolet rays at 205nm and 255nm. Compared with the infrared spectrum of a ligand, the infrared spectrum of the complex 1 shows that a C-N bond of the complex 1 extends, shrinks, vibrates and moves with 10cm<-1>. The synthesizing method has the advantages that the experiment result shows that the complex has stronger anti-bacterial activity on achromobacter xylosoxidans, bacillus subtilis, candida albicans, candida drusei, candida glabrata, cryptococcus neoformans, aspergillus niger, aspergillus terreus, aspergillus fumigatus, aspergillus flavus and the like; the complex can be used as a good novel bacteriostatic agent product.
Description
Technical field
The invention belongs to inorganic chemistry, organic chemistry, biological chemistry and medicinal chemistry art, relate to the research of the synthesis of metal complexes, structure elucidation, ultraviolet, infrared and anti-microbial activity.
Background technology
Metal complexes has potential application at subjects such as environmental science, Materials science, life sciences.Metal complexes can store gas and divided gas flow (Y.He, W.Zhou, G.Qian, B.Chen, Chem.Soc.Rev.2014,43,5657-5678; Z.Zhang, Y.Zhao, Q.Gong, Z.Li, J.Li, Chem.Commun., 2013,49,653-661); The title complex of Zn (II) and Cd (II) can react (P.Li, S.Regati, R.J.Butcher, H.D.Arman by catalysis Biginelli effectively, Z.Chen, S.Xiang, B.Chen, C.G.Zhao, TetrahedronLett., 2011,52,6220-6222); The title complex of cuprous salt has special optical property (S.Hu, F.-Y.Yu, P.Zhang, D.-R.Lin, DaltonTrans., 2013,42,7731-7740).Therefore, design and development New function metal complexes still also exists challenge.
The research of the synthesis of nearest pharmaceutical complex, activity and structure activity relationship is subject to extensive concern, and achieve certain progress (Li Haixia, Chen Rong, Liu Yonggen. antibacterial metal title complex drug research As-Is analysis. Chinese Chinese materia medica academic periodical, 2010,28(12): 2580-2582).Cys contracting o-vanillin Cu (II) title complex, 4,4 '-diaminodiphenylmethane contracting o-vanillin schiff bases Cu (II) title complex and 4,4 '-diaminodiphenylmethane contracting o-vanillin schiff bases Fe (II) title complex to the inhibition of tumor cell proliferation better (Liu Shanbin. the synthesis of Novel transition metal complex, sign and applied research: [D]. Qingdao: Chemistry and Chemical Engineering College of Chinese Marine University, 2011); With the aminocompound of different structure and indoles-2, the 3-diketone serial schiff base compounds that has been Material synthesis, then obtain series metal title complex with this serial part.Research shows, [CdL
3(CH
3cOO)] H
2o (C1), [CoL
4(CH
3cOO)] 3H
2o (C3) and [ZnL
6(CH
3cOO)] 3H
2o (C5) propagation to human breast cancer cell have good restraining effect (Zhang Peng flies. the synthesis characterization of indoles-2,3-diones schiff bases complex and bioactivity research: [D]. Qingdao: Chemistry and Chemical Engineering College of Chinese Marine University, 2014).
Voriconazole is a kind of New-type wide-spectrum antifungal drug in triazole class, can the demethylation of 14 α-sterol of Antifungi cytochrome P 450 mediated, thus the synthesis of Antifungi ergosterol.Voriconazole suppresses yeast also to kill some thread organism, compares saccharomycetic higher the affinity of the lanosterol 14 α-demethyl enzyme of mould, ergosterol can be made to synthesize and be obstructed completely, cause necrocytosis.Voriconazole is a heterocyclic organic ligands containing triazole ring, therefore synthesizes and the metal complexes that designs this kind of triazole ring has important research meaning.
Therefore synthesize and a kind ofly there is anti-microbial activity title complex and study its antibacterial character, for the suitability for industrialized production of this title complex and bacteriostatic activity application thereof provide foundation.
Summary of the invention
The present invention solves the problem of the shortcomings such as the synthesis cost of existing fungistat is high and anti-microbial activity is low, provide a kind of synthetic method with the voriconazole neutralized verdigris title complex of anti-microbial activity, this compound bacteriostatic activity is strong, its preparation method is simple, generated time is short, and raw material sources is sufficient and of many uses.This compound is a new compound, has no bibliographical information.
The invention provides a kind of synthetic method with anti-microbial activity title complex, and its structure, spectral quality, anti-microbial activity are studied.
Concrete synthesis step of the present invention.
The synthesis of embodiment one, title complex
By voriconazole (FZ) 0.035g(0.1mmol) and 0.019965g(0.1mmol) the water-soluble and methyl alcohol of neutralized verdigris mixed solution in, then transferred in flask by reaction solution and heat, temperature of reaction is 65 degree.Reaction solution is down to room temperature after reacting 10 minutes, moves in test tube.Mazarine bulk crystals 1 is obtained after 5 days.Products obtained therefrom 1 is determined its molecular structure through Advances in crystal X-ray diffraction analysis, sees Fig. 1.
The germ resistance of product 1 and part FZ is tested, its anti-microbial activity (MIC-
50, μ gmL
-1) in table one, two.
Above-mentioned a kind of synthetic method with the voriconazole neutralized verdigris title complex of anti-microbial activity, this compound can be used as excellent Antibiogics usage.
Beneficial effect of the present invention: the present invention is that a kind of voriconazole neutralized verdigris title complex with anti-microbial activity obtains under solvent-thermal process condition, preparation method's technique is simple, easy to operate, generated time is short, and productive rate is high, and reaction fast, sufficient raw, low production cost, the fault in material be synthesized is few, and degree of crystallinity is high.Experiment favorable reproducibility, environmental friendliness.This title complex has excellent potential application prospect in biological activity field, can be applied to antibacterial agent.
Accompanying drawing explanation
The crystalline structure figure of Fig. 1, compound 1.
The ultraviolet spectrogram of Fig. 2, compound 1.
The infrared spectrogram of Fig. 3, compound 1.
Embodiment
Be described in detail embodiments of the invention below, the present embodiment is implemented under premised on technical solution of the present invention, give detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.
The invention provides a kind of synthetic method of title complex, and the character such as its ultraviolet, infrared and anti-microbial activity are studied.
For achieving the above object, by voriconazole and the water-soluble and methyl alcohol of neutralized verdigris, then transferred in flask by reaction solution and heat, temperature of reaction is 65 degree.Reaction solution is down to room temperature after reacting 10 minutes, is moved in test tube by reaction solution.Mazarine bulk crystals 1 is obtained after 5 days.Products obtained therefrom 1 is determined its molecular structure through Advances in crystal X-ray diffraction analysis, sees Fig. 1.
Concrete synthesis step of the present invention is as follows.
The synthesis of embodiment one, product 1
By voriconazole (FZ) 0.035g(0.1mmol) and 0.019965g(0.1mmol) the water-soluble and methyl alcohol of neutralized verdigris mixed solution in, then reaction solution is transferred in flask and is heated, and temperature of reaction is 65 degree.Reaction solution is down to room temperature after reacting 10 minutes, and moves in test tube.Mazarine bulk crystals 1 is obtained after 5 days.Products obtained therefrom 1 is determined its molecular structure through Advances in crystal X-ray diffraction analysis, sees Fig. 1.
The above embodiment only have expressed embodiments of the present invention; it describes comparatively concrete and detailed; but therefore can not be interpreted as the restriction to the scope of the claims of the present invention; in every case the technical scheme adopting the form of equivalent replacement or equivalent transformation to obtain, all should drop within protection scope of the present invention.
Claims (8)
1. have a synthetic method for the voriconazole neutralized verdigris title complex of anti-microbial activity, this title complex can be used as excellent antibacterial medicine,
It is characterized in that:
(1) synthesis of embodiment one, title complex 1
A certain proportion of voriconazole (FZ) and neutralized verdigris are dissolved in a certain amount of water and organic solvent, then solution is transferred in flask, be down to room temperature after having heated, filter, leave standstill, separate out the target product 1 of mazarine bulk and determine its crystalline structure
(2) biological activity of embodiment two, metal acetate copper complex
Its anti-microbial activity measuring process: get after appropriate product 1 and part FZ be dissolved in suitable solvent for some time at moderate temperatures, measure its anti-microbial activity.
2. the synthesis of the title complex according to claims 1 and purposes, is characterized in that the chemical formula of described title complex is [Cu
2(FZ)
2(CH
3cOO)
2(H
2o)] 2H
2o.
3. the synthesis of the title complex according to claims 1 and purposes, is characterized in that selected temperature range is from room temperature to 100 degrees Celsius.
4. the synthesis of the title complex according to claims 1 and purposes, is characterized in that heat-up time was from 5 minutes to 30 minutes.
5. the synthesis of the title complex according to claims 1 and purposes, it is characterized in that selected organic solvent to be carbon atom quantity be single solvent or the mixed solvent of the unit alcohol of 1-10, acetone, ethyl acetate, dimethyl sulfoxide (DMSO), DMF, methylene dichloride, trichloromethane, tetracol phenixin, Nitromethane 99Min., tetrahydrofuran (THF), N-Methyl pyrrolidone, sherwood oil, benzene, toluene.
6. the synthesis of the title complex according to claims 1 and purposes, is characterized in that the ratio of water and organic solvent is 1:0.1 ~ 1:15.
7. the synthesis of the title complex according to claims 1 and purposes, is characterized in that the ratio of voriconazole (FZ) and cupric nitrate is 1:0.1 ~ 1:5.
8. the synthesis of the title complex according to claims 1 and purposes, it is characterized in that such title complex Achromobacter xylosoxidans, Bacillus subtilus, Candida albicans, candida krusei, Candida glabrata, Cryptococcus neoformans, aspergillus niger, terreus, Aspergillus fumigatus, flavus etc. have strong bacteriostatic activity, this title complex can be used as excellent new bacteriostatic agent product.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610010387.8A CN105440062A (en) | 2016-01-08 | 2016-01-08 | Synthesizing method of voriconazole copper acetate complex with anti-bacterial activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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| WO1999010017A1 (en) * | 1997-08-26 | 1999-03-04 | Board Of Regents, The University Of Texas System | Chelators in combination with biocides: treatment of microbially induced biofilm and corrosion |
| CN105622642A (en) * | 2016-01-09 | 2016-06-01 | 齐鲁工业大学 | Voriconazole copper nitrate complex with bacteriostatic activity and preparation method thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999010017A1 (en) * | 1997-08-26 | 1999-03-04 | Board Of Regents, The University Of Texas System | Chelators in combination with biocides: treatment of microbially induced biofilm and corrosion |
| CN105622642A (en) * | 2016-01-09 | 2016-06-01 | 齐鲁工业大学 | Voriconazole copper nitrate complex with bacteriostatic activity and preparation method thereof |
Non-Patent Citations (2)
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| JUSTYNA NAGAJ ET AL.: ""The Cu(II)-fluconazole complex revisited. Part I: Structural characteristics of the system"", 《JOURNAL OF INORGANIC BIOCHEMISTRY》 * |
| ZABEK, ADAM ET AL.: ""Activity of fluconazole and its Cu(II) complex towards Candida species"", 《MED CHEM RES》 * |
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