CN102491997A - Cholic acid-molybdenum polyoxometallate-cholic acid compound and synthetic method - Google Patents

Cholic acid-molybdenum polyoxometallate-cholic acid compound and synthetic method Download PDF

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CN102491997A
CN102491997A CN2011103776453A CN201110377645A CN102491997A CN 102491997 A CN102491997 A CN 102491997A CN 2011103776453 A CN2011103776453 A CN 2011103776453A CN 201110377645 A CN201110377645 A CN 201110377645A CN 102491997 A CN102491997 A CN 102491997A
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cholic acid
metal oxygen
molybdenum
oxygen hydrochlorate
molybdenum multi
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王维
杨海宽
苏明明
李秋月
胡敏标
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Nankai University
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Abstract

The invention provides a cholic acid-molybdenum polyoxometallate-cholic acid compound which has a chemical formula of [(n-Bu)4N]3{MnMo6O18[(OCH2) 3CNHCOC23H39O3] 2}. A synthetic method for the compound is as follows: based on the characteristic that chemical modification of cholic acid molecules is easy since a steroid ring of a cholic acid molecule has three hydroxyl groups and one carboxyl groups, an organic-inorganic hybridization method is used for chemical modification of molybdenum polyoxometallate so as to form the covalently linked cholic acid -molybdenum polyoxometallate-cholic acid compound. The compound has strong biological compatibility, high transport capacity, small toxic and side effects and potential targeting positioning effects and anticancer functions and has a potential application value in the fields of surfactants, bio-carriers, catalysts and the like; the synthetic method has the advantages of a simple process, mild conditions, a short reaction period, capacity of producing a high purity product and convenience in industrial production, popularization and application.

Description

A kind of cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds and compound method
Technical field
The present invention relates to the synthetic technology of hybrid inorganic-organic macromolecular cpd, particularly a kind of cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds and compound method.
Background technology
Polyoxometallate is the one type of negatively charged ion unit molecule cluster compound with definite structure that is formed through oxygen coordination bridging by the early transition metal atom, serves as main representative with elements such as vanadium, molybdenum, tungsten wherein.At biology, medical science and pharmaceutical field, people know that very early polyoxometallate can make the vegeto-alkali deposition, make protein condenses.Toxicologic study, the prudence of the separation of medicine, evaluation, chemical toxicant identify and the analysis of biomaterial in, polyoxometallate is used as precipitation agent, oxygenant and developer widely.In recent years, polyoxometallate is used in polypeptied chain, protein, enzyme catalysis and the photosynthetic biological study, and it makes the pharmaceutical chemistry develop rapidly of polyoxometallate in pharmaceutical chemical significant application value and excellent development prospect.The biological activity of polyoxometallate mainly comprises the following aspects: anti-tumor activity, antiviral activity and the anti-AIDS cytotoxic activity of the height of enzyme function being selected inhibition, vivo and vitro.
Polyoxometallate is because possess above-mentioned various advantages, and its correlative study has attracted the numerous scholars' in field such as chemistry, biology, medical science common concern.Yet, up to now till because the stronger toxicity of polyoxometallate itself, also do not have polyoxometallate to be used as medicine and be used for clinically, its great toxicity has also limited its progressively development aspect biological, medical simultaneously.
Cholic acid is the abundantest a kind of of content in human four kinds of main bile acides, is the one type of biologically active existing in the human body and the amphipathic molecule (wetting ability and oleophilicity) of biocompatibility.Cholic acid is in liver cell, to be raw material synthetic under the enzyme catalysis condition with the SUV; Be the main mode of hepatic clearance SUV, treatment plays an important role to reducing cholesterol, and cholic acid is drained in the duodenum with bile simultaneously; As one of integral part of Digestive system; In intestines, help greasy hydrolysis and absorption, can promote digestion and absorption to lipid material and liposoluble vitamin, some cholic acid also has antispastic, is good for the stomach, reduces in the blood effect such as cholesterol content in addition.1996, Dayal prepared a series of cholic acid conjugates through the chemical synthesis that cholic acid compounds and taurine compound form amido linkage, had promoted the application of this exogenous cholic acid compounds aspect the treatment hepatobiliary system disease; 1998, Boos etc. reported under dehydrating agent DCC and catalyzer DMAP condition, have prepared the hydroxy esterification polymerisable monomer of methylacrylic acid and Methyl cholate or Septochol methyl esters, the SUV in the alternative adsorbent solution of final imprinted polymer; 2004, Mukhopadhyay and Maitra summarized the application of bile acide compounds at aspects such as physiological function, pathology and pharmacology, for example can promote the dissolving and the absorption of liposoluble vitamin, keep SUV homeostasis etc.
The present invention utilizes cholic acid, adopts the method for hybrid inorganic-organic, and molybdenum multi-metal oxygen hydrochlorate is carried out chemical modification, has synthesized the hydridization molecule cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid that in existing report, does not have.Purpose is through being the specific natural aglucon of endogenic liver cell by cholic acid, having bio-compatibility preferably, the organ specificity of height and a higher turn-over capacity; With the cholic acid is targeting vector; Give the target positioning action function of the molybdenum multi-metal oxygen hydrochlorate target molecule of potential drug characteristic; Not only can realize the target property of medicine; Reduce toxic side effect, the receptivity of cancer therapy drug and organ are had important potential using value to the selectivity of medicine improving vitals such as liver.
Summary of the invention
The objective of the invention is to above-mentioned technical Analysis, provide that a kind of bio-compatibility is strong, transportcapacity is high, toxic side effect is low, have the cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds and the compound method of potential target positioning action and anti-cancer function.
Technical scheme of the present invention:
A kind of cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds, its chemical formula is:
[(n-Bu) 4N] 3{MnMo 6O 18[(OCH 2) 3CNHCOC 23H 39O 3] 2}。
The compound method of a kind of said cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds, step is following:
1) with 2-oxyethyl group-1-ethoxy carbonic acyl radical-1, the 2-EEDQ joins in the acetonitrile solvent, under the reflux conditions, adds the cholic acid reaction after 30-45 minute, adds [(n-Bu) 4N] 3{ MnMo 6O 18[(OCH 2) 3CNH 2] 2, refluxed 36 hours, obtain reaction solution;
2) above-mentioned reaction solution is cooled to room temperature; Reaction solution is concentrated after-filtration, and filtrating is precipitated in THF, the product behind the suction filtration is dissolved in the acetonitrile solvent again; After in ether steam, slowly precipitating 2-4 days; Separate out orange solids, the product behind the suction filtration is dry, promptly get said cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds.
Said 2-oxyethyl group-1-ethoxy carbonic acyl radical-1, the amount ratio of 2-EEDQ and acetonitrile solvent is 2.0-3.0/1mL.
Said 2-oxyethyl group-1-ethoxy carbonic acyl radical-1,2-EEDQ, cholic acid and [(n-Bu) 4N] 3{ MnMo 6O 18[(OCH 2) 3CNH 2] 2Mol ratio be 10.5-19.5: 7.0-13.0: 1.0.
Concentration ratio before and after said filtrating concentrates is 1: 15-20, filtrating is 1 with the volume ratio of THF: 25-30.
The product behind the said suction filtration and the amount ratio of acetonitrile solvent are 65-75mg/1mL.
The synthetic route of said cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds is represented as follows:
Figure BDA0000112366420000031
Advantage of the present invention is: utilize on the cyclopentanoperhydro-phenanthrene of cholic acid molecule and be connected with three hydroxyls and a carboxyl, the characteristics that are easy to carry out chemically modified adopt the method for hybrid inorganic-organic, and molybdenum multi-metal oxygen hydrochlorate is carried out chemical modification, through cholic acid with [(n-Bu) 4N] 3{ MnMo 6O 18[(OCH 2) 3CNH 2] 2Reaction, synthesising biological is compatible strong, transportcapacity is high, toxic side effect is low, have the cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid hydridization molecule of potential target positioning action and anti-cancer function; This synthetic method craft is simple, mild condition, reaction time is short, product purity is high, is convenient to realize suitability for industrialized production and applies.
Description of drawings
Accompanying drawing 1 is the FT-IR ir spectra spectrogram of cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds.
Accompanying drawing 2 is the H of cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds 1The nuclear magnetic resonance, spectrum spectrogram.
Embodiment
Below in conjunction with embodiment the present invention is made further and to specify, but the present invention is not limited to this embodiment.
Embodiment:
The compound method of a kind of said cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds, step is following:
1) with 2-oxyethyl group-1-ethoxy carbonic acyl radical-1,2-EEDQ (EEDQ) 493mg and 200mL acetonitrile solvent under refluxad, add dehydrocholic acid 544mg, react after 40 minutes, add [(n-Bu) 4N] 3{ MnMo 6O 18[(OCH 2) 3CNH 2] 2250mg, reflux after 36 hours, obtain reaction solution;
2) behind the cool to room temperature, reaction solution is concentrated to 10mL, filters out white precipitate; To filtrate and in the 300mL THF, precipitate, the product behind the suction filtration is dissolved in the 4mL acetonitrile solvent, and slow deposition is after three days in ether steam; Separate out orange solids; Product behind the suction filtration is dry, promptly get title product, productive rate 78%.
Cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid the compounds of preparation is passed through IR, H respectively 1Nuclear magnetic resonance spectrometer and elemental analyser detect.
Accompanying drawing 1 is the infrared spectrogram of cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds, and this infrared spectrogram shows: 1030,941,920,902,667,564cm -1The characteristic peak of the polyoxometallate at place has all obtained good reservation in the hydridization molecule, thereby has confirmed that polyoxometallate structure after the reaction neutralization reaction has all kept complete; 3332cm -1The peak be the stretching vibration peak of N-H, 1669cm -1Be the stretching vibration peak of C=O, 1542cm -1Be the flexural vibration peak of N-H, 1255cm -1Be the stretching vibration peak of C-N, the existence at these peaks has proved the existence of amido linkage in the hydridization molecule, thereby confirms that between polyoxometallic acid molecules of salt and the cholic acid be covalently bound.
Fig. 2 is the H of cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds 1The nuclear magnetic resonance, spectrum spectrogram, all there is good ownership at each peak among the figure, and wherein ☆ representes solvent peak, and * representes the water peak, thereby has confirmed that we have successfully prepared cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds.
Following subordinate list is the results of elemental analyses of cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid class hybrid.
Subordinate list
Title C/％ H/％ N/％
Cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid Theoretical content 46.90 7.57 2.63
Test content 46.64 7.71 2.87
The subordinate list data presentation: experiment test result and notional result are more close, thereby have proved that cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds purity is better.

Claims (6)

1. cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds is characterized in that chemical formula is:
[(n-Bu) 4N] 3{MnMo 6O 18[(OCH 2) 3CNHCOC 23H 39O 3] 2}。
2. compound method of cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds according to claim 1 is characterized in that step is following:
1) with 2-oxyethyl group-1-ethoxy carbonic acyl radical-1, the 2-EEDQ joins in the acetonitrile solvent, under the reflux conditions, adds the cholic acid reaction after 30-45 minute, adds [(n-Bu) 4N] 3{ MnMo 6O 18[(OCH 2) 3CNH 2] 2, refluxed 36 hours, obtain reaction solution;
2) above-mentioned reaction solution is cooled to room temperature; Reaction solution is concentrated after-filtration, and filtrating is precipitated in THF, the product behind the suction filtration is dissolved in the acetonitrile solvent again; After in ether steam, slowly precipitating 2-4 days; Separate out orange solids, the product behind the suction filtration is dry, promptly get said cholic acid-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds.
3. according to the compound method of the said cholic acid of claim 2-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds, it is characterized in that: said 2-oxyethyl group-1-ethoxy carbonic acyl radical-1, the amount ratio of 2-EEDQ and acetonitrile solvent is 2.0-3.0mg/1mL.
4. according to the compound method of the said cholic acid of claim 2-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds, it is characterized in that: said 2-oxyethyl group-1-ethoxy carbonic acyl radical-1,2-EEDQ, cholic acid and [(n-Bu) 4N] 3{ MnMo 6O 18[(OCH 2) 3CNH 2] 2Mol ratio be 10.5-19.5: 7.0-13.0: 1.0.
5. according to the compound method of the said cholic acid of claim 2-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds, it is characterized in that: the concentration ratio before and after said filtrating concentrates is 1: 15-20, filtrating is 1 with the volume ratio of THF: 25-30.
6. according to the compound method of the said cholic acid of claim 2-molybdenum multi-metal oxygen hydrochlorate-cholic acid compounds, it is characterized in that: the product behind the said suction filtration and the amount ratio of acetonitrile solvent are 65-75mg/1mL.
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CN105012342A (en) * 2015-05-25 2015-11-04 暨南大学 Polypeptide functionalized nanometer molybdenum polyoxometallate, and preparation method and application thereof
CN105859820A (en) * 2016-03-31 2016-08-17 中北大学 Folic acid-coated dehydrocholic acid-polyxomolybdates-pyrene hybrid and preparation method thereof
CN109021017A (en) * 2018-08-06 2018-12-18 厦门大学 Hydrochlorate reactive flame retardant of oxygen containing molybdenum multi-metal and preparation method thereof
CN111072723A (en) * 2019-12-27 2020-04-28 湖北工业大学 Organic derivative of Anderson polyacid modified by monoiodo benzoic acid through covalent bond and application of organic derivative in resisting ADV7 virus
CN113718519A (en) * 2021-09-14 2021-11-30 三河市安霸生物技术有限公司 Antiviral finishing agent, antiviral fabric and preparation method thereof
CN115572302A (en) * 2022-09-29 2023-01-06 山东第一医科大学(山东省医学科学院) Podophyllotoxin modified polyoxometallate hybrid compound and preparation method and application thereof

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105012342A (en) * 2015-05-25 2015-11-04 暨南大学 Polypeptide functionalized nanometer molybdenum polyoxometallate, and preparation method and application thereof
CN105012342B (en) * 2015-05-25 2018-08-28 暨南大学 A kind of molybdenum multi-metal oxygen silicate nanometer of polypeptide functionalization and its preparation method and application
CN105859820A (en) * 2016-03-31 2016-08-17 中北大学 Folic acid-coated dehydrocholic acid-polyxomolybdates-pyrene hybrid and preparation method thereof
CN109021017A (en) * 2018-08-06 2018-12-18 厦门大学 Hydrochlorate reactive flame retardant of oxygen containing molybdenum multi-metal and preparation method thereof
CN109021017B (en) * 2018-08-06 2020-02-11 厦门大学 Molybdenum-containing polyoxometallate reaction type flame retardant and preparation method thereof
CN111072723A (en) * 2019-12-27 2020-04-28 湖北工业大学 Organic derivative of Anderson polyacid modified by monoiodo benzoic acid through covalent bond and application of organic derivative in resisting ADV7 virus
CN111072723B (en) * 2019-12-27 2022-10-11 湖北工业大学 Anderson polyacid organic derivative modified by monoiodo benzoic acid through covalent bond and application of Anderson polyacid organic derivative in resisting ADV7 virus
CN113718519A (en) * 2021-09-14 2021-11-30 三河市安霸生物技术有限公司 Antiviral finishing agent, antiviral fabric and preparation method thereof
CN113718519B (en) * 2021-09-14 2023-09-26 三河市安霸生物技术有限公司 Antiviral finishing agent, antiviral fabric and preparation method thereof
CN115572302A (en) * 2022-09-29 2023-01-06 山东第一医科大学(山东省医学科学院) Podophyllotoxin modified polyoxometallate hybrid compound and preparation method and application thereof
CN116870177A (en) * 2022-09-29 2023-10-13 山东第一医科大学(山东省医学科学院) Podophyllotoxin modified polyoxometallate hybrid compound and preparation method and application thereof
CN116870177B (en) * 2022-09-29 2024-03-08 山东第一医科大学(山东省医学科学院) Podophyllotoxin modified polyoxometallate hybrid compound and preparation method and application thereof

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Application publication date: 20120613