CN102993151A - Flavanol compound, and preparation method and application thereof - Google Patents
Flavanol compound, and preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a natural medicine, and particularly relates to novel flavanol compound in a Uraria clarkei, and a preparation method and application thereof. The invention provides the flavanol compound, and the preparation method and application thereof. The flavanol compound is separated and prepared from the Uraria clarkei. The structural formula of the compound is a formula (I) shown in the specification. The preparation method of the compound in the formula (I) comprises the steps of a, crushing; b, extracting by refluxing; c, concentrating; d, extracting, and e, separating. The compound in the formula (I) prepared by the preparation method provided by the invention has significant anti-cancer activity and activity of resisting marine fouling organisms, has obvious inhibition effect on cells of tumors, human cervical carcinoma, human chronic myeloid leukemia or human acute myelogenous leukemia, has good antitumor activity and good application prospect, also displays strong activity of inhibiting biofouling, and can provide valuable pilot compounds for development of an anti-fouling paint or other anti-fouling products.
Description
Technical field
The present invention relates to a kind of natural drug, be specifically related to a kind of new flavanols compounds and its preparation method and application in the wild kind beans.
Background technology
Cancer has developed into common disease, the frequently-occurring disease of serious harm people life, and same cardiovascular and cerebrovascular disease, diabetes are called as one of the world three large Deaths together.The World Health Organization issues in February, 2010 and reports, the whole world will have 7,600,000 people to die from cancer to estimate the current year, if the half-hearted preventing cancer of taking measures of people may be doubled on existing basis to the annual cancer mortality number in the year two thousand thirty whole world, reach 1,700 ten thousand.This tissue statistic data also shows just have 1 people to die from cancer in average per 8 deaths in the whole world at present, and this is more taller than the death toll summation that acquired immune deficiency syndrome (AIDS), tuberculosis and malaria cause.Therefore seeking effective cancer therapy drug has become the task of top priority.In cancer therapy drug research, the studies and clinical application of chemotherapeutics has been obtained remarkable progress.Although have strong cancer resistance, there are toxic side effect in the cancer therapy drug of chemosynthesis such as metal complexes platinum complex, organic germanium compounds etc., the defectives such as poorly water-soluble.In recent years, the researchist of China and foreign countries turns one's attention to herbal medicine, the ethnic drug of aboundresources, pure natural gradually, wishes therefrom to seek new cancer therapy drug.From herbal medicine, ethnic drug, found at present a series of natural anti-cancer drugs such as taxol, camptothecine, kind of harringtonine as medicinal materials, vincristine(VCR), podophyllotoxin, Elemenum Emulsion, and many new product listings have been arranged every year.These natural drugs have all showed good antitumour activity and have been widely used clinically, prove day by day that also screening antineoplastic drugs is a very promising direction from natural product.
Wild kind beans (
Uraria clarkeiGagnep) be pulse family (Leguminosae) leopard cat tail bean plant (72 pages of " Chinese Plants will " the 41st volumes).This platymiscium whole world has 20 kinds approximately, is distributed in Tropical Africa, Asia and Australia, and China has 9 kinds, and most kinds concentrate on 25 ° of areass to the south of north latitude.(Chen Yan thinks the elegant tinkling of pieces of jade, Wei Song, Xu Xuejian according to document.The research [J] of rabbit tail grass chemical ingredients. Chinese patent medicine, 2009,31 (2): 266-269) report, this platymiscium have the effects such as treatment infantile malnutrition, puerperal lactation deficiency, hemoptysis, hemorrhoid, the tuberculosis of cervical lymph nodes, venomous snake bite.The result of study of this platymiscium shows that its chemical ingredients is mainly flavonoid compound, comprises the structure types such as flavones, isoflavones, isoflavanone.Less to the research report of wild kind beans plant chemical ingredient and pharmacologically active at present.
Biodeterioration, refer to that marine organisms such as algae, crustaceans etc. are gathered in any position of hull, comprise shell, rudder, water screw and other hull attachments, or ship maritime interior waters system such as sea chest, engine cool pipeline, boat-carrying and auxiliary facility, or the biogenic accumulation and the fouling that form on the movement such as aquaculture facility or the fixation means.In recent years, along with the development of shipping, coast defence, aquaculture and coastal power plant etc., the halobiontic stained harm that brings is more and more serious.Develop at present the most soon, the pollution control damage method that is most widely used is for applying the high-efficiency pollution-proof lacquer.Generally adopt the antifouling paint that contains toxic chemical (such as Red copper oxide, copper pyrithione, Irgarol 1051, Econea etc.) to prevent and kill off, but these toxic substances continue to discharge to ocean environment, particularly at ship movable intensive naval port and civil harbor, poisonous substance often reaches high level, causes serious marine pollution matter.Red copper oxide is a kind of stain control agent that is most widely used at present, it has antifouling activity to the overwhelming majority's animal class marine life and most plant marine lifes, but not good to soft stained marine life anti-fouling effect, need to add auxiliary stain control agent and reach comprehensive anti-fouling effect.Because copper can especially gather in the harbour in the ocean in a large number, produce " black pollution ".Red copper oxide decomposes the cupric ion that produces in seawater, the apoenzyme that marine life is depended on for existence loses activity, or makes the flocculation of biomass cells protein produce the metalloprotein throw out, causes biological tissue to change and death.
Traditional stain control agent has toxic action to settled organism, causes expendable damage, and pollutes the environment, and destroy the eubiosis, and desirable marine antifoulant should satisfy simultaneously: have activity under (1) lower concentration; (2) economy; (3) harmless to human body and other organism; (4) be applicable to various attaching substratums; (5) pollution-free; (6) has biodegradability.Natural product stain control agent in the bionical antifouling paint or its analogue through chemical modification, easily degraded, and do not endanger biological life, and be conducive to keep ecological balance, be one of important channel of exploitation non-toxic efficient antifouling paint.Many materials with anti-fouling activity from ocean and terrestrial life, have been found at present, the material that comprises the types such as terpene, alkynes class, polynuclear compound, steroide, isothiocyanate, part of compounds has wherein shown preferably repellency to marine fouling organism, but lower or be safe from harm to the harm of water body environment.
Summary of the invention
For solving the problem that exists in the background technology, the invention provides a kind of new flavanols compounds with significant anticancer and anti-marine fouling organism activity.
Another object of the present invention provides a kind of method of extracting flavanols compounds of the present invention from wild kind beans.
Further aim of the present invention is the application of flavanols compounds in preparation prevention or medicine for treating tumor thing of adopting preparation method of the present invention to make.
Further aim of the present invention is the application of flavanols compounds in preparing prevention or treatment human cervical carcinoma, people's chronic myelogenous leukemia, human acute myeloid leukemia medicine of adopting preparation method of the present invention to make.
Further aim of the present invention be adopt flavanols compounds that preparation method of the present invention makes prevent the underwater structure surface be subject to halobiontic adhere to and/or stained aspect application.
Further aim of the present invention be adopt flavanols compounds that preparation method of the present invention makes prevent that marine organisms from adhering to and/or stained aspect application, wherein said marine organisms are that the barnacle class is biological.
For reaching above purpose, the present invention by the following technical solutions:
Except as otherwise noted, the percentage ratio that adopts among the present invention is mass percent.
The present invention isolates a kind of new flavanols compounds from wild kind beans, it is active that this compound has significant anticancer and anti-marine fouling organism.
New flavanols compounds of the present invention has the structural formula shown in the formula I:
The called after of this compound: (2R, 4R)-2 ', 4 '-dihydroxyl-5,7-dimethoxy flavane-4-alcohol ((2R, 4R) 2 ', 4 '-dihydroxy-5,7-dimethoxyflavan-4-ol).
A kind of preparation method of flavanols compounds may further comprise the steps:
A, pulverizing: with getting meal after kind beanstalk dried and crushed of open country, for subsequent use;
B, refluxing extraction: the meal that step a is made merges ethanol extract with alcohol reflux four times, and is for subsequent use;
C, concentrated: carry out concentrating under reduced pressure after the ethanol extract that step b is made filters and get medicinal extract, for subsequent use;
D, extraction: the medicinal extract that step c is made is suspended in the water, extracts with sherwood oil, ethyl acetate and propyl carbinol successively, removes solvent again, gets respectively sherwood oil, ethyl acetate and n-butyl alcohol extract, and is for subsequent use;
E, separation: the acetic acid ethyl ester extract that steps d is made is through 100 ~ 300 order silica gel column chromatographies, petroleum ether-ethyl acetate gradient elution with volume ratio 20:1,10:1,5:1,2:1,1:1,0:1 obtains Fr.1 ~ Fr.6 totally 6 components, Fr.3 is through silica gel column chromatography, chloroform with volume ratio 98:2,95:5,90:10: the methyl alcohol gradient elution obtains component Fr.3A～3C.Fr.3C is through silica gel column chromatography, and with the chloroform of volume ratio 80:20: the acetone wash-out obtains formula I compound through Sephadex LH-20 column chromatography methyl alcohol purifying again.
The present invention has carried out cell toxicant and the test of anti-marine fouling organism attachment activity to flavanols compounds, experimental result demonstrates good inhibition human cervical carcinoma, people's chronic myelogenous leukemia, the human acute myeloid leukemia cell strain is active and anti-marine fouling organism attachment activity, can be new compound or lead compound that medical industry and marine antifouling industry provide using value.
Beneficial effect
1, the flavanols compounds that adopts preparation method of the present invention to make has significant restraining effect to tumour, human cervical carcinoma, people's chronic myelogenous leukemia or human acute myeloid leukemia cell, has good antitumour activity.Good drug development prospect is arranged, can be used as anticancer active constituent or lead compound.
2, it is active that the flavanols compounds that adopts preparation method of the present invention to make also shows stronger inhibition biodeterioration, and the exploitation that can be fouling resistance coating or other fouling resistance product provides valuable lead compound, and good application prospect is arranged.
3, the flavanols compounds that adopts preparation method of the present invention to make is naturally occurring organic compound, be non-toxic compound, easily degraded in ocean environment, can not cause the pollution of water body environment, can not cause its enrichment in organism by the food chain transmission, environmentally friendly, safe.
Description of drawings
Fig. 1 is the compounds of this invention high resolution mass spectrum (HRESI-MS).
Fig. 2 be the compounds of this invention proton nmr spectra (
1H NMR).
Fig. 3 be the compounds of this invention carbon-13 nmr spectra (
13C NMR).
Fig. 4 is the DEPT spectrum of the compounds of this invention.
Fig. 5 is the COSY spectrum of the compounds of this invention.
Fig. 6 is the HSQC Correlated Spectroscopy of the compounds of this invention.
Fig. 7 is the HMBC Correlated Spectroscopy of the compounds of this invention.
Fig. 8 is the CD spectrum of the compounds of this invention.
Fig. 9 is the structural formula of the compounds of this invention.
Embodiment
The invention will be further described in description by following embodiment; but described only is preferred embodiment of the present invention; be not to be limitation of the present invention; the modification that those skilled in the art's basic conception according to the present invention is made; only otherwise break away from basic thought of the present invention, all within protection scope of the present invention.
Embodiment 1:A kind of preparation method of flavanols compounds
Material source: wild kind beans are adopted in Yunnan, and Tao Deding researcher is accredited as through Kunming Inst. of Botany, Chinese Academy of Sciences
Uraria clarkei(Clarke) Gagnep., sample are stored in Yunnan Institute for nationalitiesization and give birth to institute sample shop.
A kind of preparation method of flavanols compounds may further comprise the steps:
A, pulverizing: be ground into the meal of particle diameter 0.2cm size after wild kind beanstalk dried, for subsequent use;
B, refluxing extraction: the meal that step a is made refluxing extraction 4 times under 70 ~ 74 ℃ temperature, each 2 hours, ethanol 10 Kg with 95% concentration extract at every turn, merge ethanol extract, and were for subsequent use;
C, concentrated: the ethanol extract via hole diameter that step b is made is 80 ~ 120 microns filter paper filtering and carries out concentrating under reduced pressure under 40 ~ 50 ℃ temperature, to proportion be 1.2 o'clock, get medicinal extract 1025g, for subsequent use;
D, extraction: the medicinal extract 1025g that step c is made is suspended in the 3000ml water, extract with 3000ml sherwood oil, 3000ml ethyl acetate and 3000ml propyl carbinol successively, every kind of solvent extraction 4 times, boil off solvent with Rotary Evaporators again, get respectively sherwood oil, ethyl acetate and n-butyl alcohol extract 100g, 70g, 200g.
E, separation: the acetic acid ethyl ester extract that steps d is made is through 300 order silica gel column chromatographies, petroleum ether-ethyl acetate gradient elution with volume ratio 20:1,10:1,5:1,2:1,1:1,0:1 obtains Fr.1 ~ Fr.6 totally 6 components, Fr.1 is 10.2g, Fr.2 is 8.3g, Fr.3 is 7.0g, Fr.4 is 8.5g, Fr.5 is 6.8g, Fr.6 is 12.8g, and Fr.3 is through silica gel column chromatography, with the chloroform of volume ratio 98:2,95:5,90:10: the methyl alcohol gradient elution, obtain component Fr.3A～3C, Fr.3A is 1.4g, and Fr.3B is 1.2g, and Fr.3C is 3.8g.Fr.3C is through silica gel column chromatography, with the chloroform of volume ratio 80:20: the acetone wash-out, pass through again Sephadex LH-20 column chromatography 2000ml column volume methyl alcohol purifying, obtain faint yellow amorphous powder 150mg.
Embodiment 2:The Structural Identification of the faint yellow amorphous powder that obtains among the embodiment 1
Described faint yellow amorphous powder (solvent is methyl alcohol), [α] 21 D=-15.1 (
c=0.14, MeOH); UV (MeOH)
λ Max(log ε): 258 (3.56), 278 (3.73) nm; CD (
c=0.109, MeOH) λ (Δ ε) 242 (1.26), 280 (0.25); IR (KBr) ν
Max: 3370,2951,1603,1506,1451,1270,1107,1010 cm
-1; HRESI-MS (accompanying drawing
1) show its quasi-molecular ion peak m/z 319.0734 [M+H]
+(calcd. 319.0765) determine that in conjunction with the NMR spectrum its molecular formula is C
17H
18O
6, degree of unsaturation is 9.
1H and
13C NMR (accompanying drawing
2, accompanying drawing
3 And accompanying drawing
4, attribution data sees Table-
1) show in the molecule 2 phenyl ring (5 methyne double key carbons are arranged on the phenyl ring) are arranged, 2 methoxyl group (δ
C55.9,55.3), 2 oxygen methyne (δ even
C67.4,62.1) and 1 methylene radical (δ
C26.7).In conjunction with COSY spectrum and HSQC Correlated Spectroscopy (accompanying drawing
5And accompanying drawing
6), and documents data susceptible of proof should the yellow amorphous powder be flavanols compounds; Further through the relevant (accompanying drawing of HMBC
7) confirming that C-5, C-7 position are substituted by methoxyl group, C-4, C-2 ', C-4 ' position are substituted by hydroxyl.The absolute configuration of compound is by CD spectrum (accompanying drawing
8) and and document (Slade D, Ferreira D, Marais JPJ. Circular dichroism, a powerful tool for the assessment of absolute configuration of flavonoids. Phytochemistry, 2005,66,2177-2215) contrast turns out to be 2
R, 4
R-configuration, the structure of compound finally obtain confirming that this compound has formula I(accompanying drawing
9) shown in structural formula.Confirm that by SCIFINDER database retrieval and literature query this compound is new compound.
Table-
1. formula I compound
1H-and
13C-NMR (CDCl
3) data.
| No. | δ C | δ H |
| 2 | 67.4 | 5.28 (1H, dd, 1.6, 5.4) |
| 3 | 26.7 | 2.18 (1H, m), 2.29 (1H, m) |
| 4 | 62.1 | 5.67 (1H, dd, 4.4, 2.8) |
| 5 | 159.1 | - |
| 6 | 91.6 | 6.04 (1H, d, 2.4 ) |
| 7 | 161.9 | - |
| 8 | 92.9 | 5.99 (1H, d, 2.4 ) |
| 9 | 154.8 | - |
| 10 | 103.3 | - |
| 1' | 114.1 | - |
| 2' | 154.7 | - |
| 3' | 103.4 | 6.36 (1H, d, 2.4) |
| 4' | 157.4 | - |
| 5' | 108.2 | 6.40 (1H, dd, 8.4,2.4) |
| 6' | 131.8 | 7.22 (1H, d, 8.4 ) |
| 5-OMe | 55.9 | 3.87 (3H,s) |
| 7-OMe | 55.3 | 3.73 (3H,s) |
Embodiment 3:Different concentration ethanol solution extracts wild kind beans sample contrast experiment
Because the research report to wild kind beans chemical ingredients is few, so wish by using different concentration ethanol solution to extract wild kind beans sample, to find best ethanolic soln concentration.This is not that hint cannot be used other solvent extractions.
Concrete steps are as follows:
A, pulverizing: be ground into the particle of particle diameter 0.2 cm size after wild kind beanstalk dried, get meal, for subsequent use;
B, refluxing extraction: the meal that makes with step a under 70 ~ 74 ℃ temperature makes to extract solvent with the ethanol of 6 times of amount 70% concentration, the ethanol of 80% concentration and the ethanol of 95% concentration respectively, refluxing extraction 4 times, and each 2 hours, merge respectively ethanol extract, for subsequent use;
C, concentrated: the different concentration ethanol extracting solution via hole diameter that respectively step b is made is 80 ~ 120 microns filter paper filtering and carries out concentrating under reduced pressure under 40 ~ 50 ℃ temperature, to proportion be 1.2 o'clock, get medicinal extract, for subsequent use;
D, extraction: the medicinal extract that respectively step c is made is suspended in 3 times of water gagings, 1 times of amount of water sherwood oil, water 1 times of amount ethyl acetate and 1 times of amount of water propyl carbinol extract successively, every kind of solvent extraction 5 times, merge the same solvent extract, use again Rotary Evaporators pressure reducing and steaming solvent, get respectively sherwood oil, ethyl acetate and n-butyl alcohol extract.
Experimental result shows with the ethanol of the ethanol of the ethanol of 70% concentration, 80% concentration and 95% concentration makes to extract solvent, the open country that obtains respectively kind beans acetic acid ethyl ester extract weight approaches, therefore do to extract solvent with the ethanol of 70% concentration, the ethanol of 80% concentration and the ethanol of 95% concentration, can obtain to contain equally the composition of formula I compound.
The wild kind beans different solvents extract extract yield table of table 1.
Embodiment 4: described formula I antitumor activity of compound detects
Adopt improvement mtt assay assessing compound to the increment restraining effect of tumour cell:
Get tumour cell suspension inoculation for subsequent use in 96 well culture plates, 90 μ L/ holes, the given the test agent of adding different concns behind continuation cultivation 24 h, 10 μ L/ holes, making its final concentration is 100,10,1,0.1,0.01 μ g/mL, and each concentration is all established 3 multiple holes.The positive contrast of cis-platinum (DDP), the negative contrast of equal-volume RPMI1640 substratum.Corresponding DMSO concentration is the solvent contrast when establishing simultaneously compound 100,10 μ g/mL, to eliminate the impact of DMSO cell growth.Continue to place 37 ℃ after the dosing, 5% CO
2Incubator is cultivated 72 h, and every hole adds MTT(5 mg/mL) 20 μ L, continue to cultivate 4 h, every hole adds three liquid [10%SDS-5% isopropylcarbinol-0.012 mol/L HCl(W/V/V)], 100 μ L Rong Xie formazans.Under 570 nm wavelength, measure the OD value in each hole with microplate reader.
Calculate cell increment inhibiting rate by following formula:
Inhibiting rate (%)=(OD value control wells-OD value dosing holes)/OD value control wells * 100%
Data statistic analysis: adopt Microsoft Excel 2003 to calculate inhibiting rate, adopt the logit method, SPSS11.5 software package calculation of half inhibitory concentration IC
50
Calculation of half inhibitory concentration IC
50, to the half-inhibition concentration (IC of human cervical carcinoma (Hela), people's chronic myelogenous leukemia cell strain (k562) and human acute myeloid leukemia cell strain (HL60)
50) measurement result is respectively 13.9 ± 1.6 μ g/ml, 17.4 ± 4.3 μ g/ml, 19.1 ± 3.9 μ g/ml show that compound of the present invention has preferably anti-tumor activity.
Embodiment 5:Measure the anti-kentrogon attachment activity of described formula I compound
Adopt suppressing the experimental model that line barnacle cyprids adheres to (can be referring to scientific and technical literature: Xu Y., He H. P., Qian P. Y., et al. Potent antifouling compounds produced by marine streptomyces.
Bioresource Technology. 2010,101 (4): 1331-1336), the anti-kentrogon attachment activity of test formula I compound.Line adult barnacle (Darwin) picks up from tideland, Hong Kong (22 ° of 19'N, 114 ° of 16'E).In the polystyrene plastic culture vessel of 12 L, put into the seawater that 8 L filter, then the line adult barnacle is put into container, placement allows it discharge larva, collects larva behind 2.5 h, the larva in this stage is called naupiar larva (nauplius), does not have adhesive ability.Naupiar larva is put into the container that 8 L filtering seas (the filter membrane aperture is 0.22 μ m) is housed, bright in 24 ℃ of temperature and 15 h: aerated culture under the dark periodicity of illumination of 9 h, and feeding angle hair diatom (
Chaetoceros gracilis Schutt), the collection larva is for subsequent use later on to cultivate 3 days, and the larva in this stage is called cyprids (cypris), and adhesive ability is arranged.Formula I compound is dissolved in the methyl-sulphoxide (DMSO), then is diluted to different concentration with the sterile filtration seawater.Add 1.0 mL test fluid and 15 ± 3 cyprids in each hole of 24 well culture plates, each concentration is all established 3 multiple holes.Equal-volume sterile filtration seawater is done blank.24 well culture plates are bright in 24 ℃ of temperature and 15 h: as after cultivating 48 h under the dark periodicity of illumination of 9 h, to adhere to the number of larva in the microscopically statistics.Carry out statistical study with SPSS VIersion 11 Software of Data Statistics.
Experimental result according to the researchists' such as Rittschof method (referring to scientific and technical literature: Richard B. F., DaVIid A. Z. F., Dan R. Molting of megalopae from the blue crab Callinectes sapidus:effects of offshore and estuarine cues.
Marine ecology progress series. 1994,113:55-59) analyze.Can obtain the EC of 48 h according to experimental result
50(half suppresses to adhere to concentration, namely suppress the larva adhesive rate for maximum suppress the larva adhesive rate 50% the time corresponding concentration), by EC
50The height of detection material anti-biofouling activity as can be known.And behind 24 h, calculate the mortality of larva, can obtain the LC of 24 h according to experimental result
50(toxic limit medium dose) is by LC
50/ EC
50(toxic effect ratio) as can be known detection material is big or small to the toxicity of kentrogon.Experiment analysis results shows (2
R,4
R)-2 ', 4 '-dihydroxyl-5, the activity that 7-dimethoxy flavane-4-alcohol has remarkable inhibition line kentrogon to adhere to, concentration (EC is adhered in its half inhibition
50) be 1.2 ± 0.4 μ g/ml, toxic effect is than (LC
50/ EC
50) greater than 12.5.In addition, according to AVIelin etc. (referring to scientific and technical literature: Mary A., Mary VI., Rittschof D., Nagabhushanam R. Bacterial-barnacle interaction:potential of using juncellins and antibiotics to alter structure of bacterial communities.
J Chem. Ecol. 1993,19 (10): 2155-2167.), toxic effect is than (LC
50/ EC
50) be nontoxic anti-biofouling compound greater than the anti-biofouling compound more than 10.The toxic effect of above-claimed cpd shows that than greater than 10 this compound is nontoxic anti-biofouling compound after tested.
Claims (6)
1. flavanols compounds is characterized in that: described flavanols compounds is to separate to obtain from wild kind beans, and the structural formula of this compound is formula (I):
The called after of this compound: (2R, 4R)-2 ', 4 '-dihydroxyl-5,7-dimethoxy flavane-4-alcohol ((2R, 4R) 2 ', 4 '-dihydroxy-5,7-dimethoxyflavan-4-ol).
2. the preparation method of a kind of flavanols compounds according to claim 1 is characterized in that may further comprise the steps:
A, pulverizing: with getting meal after kind beanstalk dried and crushed of open country, for subsequent use;
B, refluxing extraction: the meal that step a is made merges ethanol extract with alcohol reflux four times, and is for subsequent use;
C, concentrated: carry out concentrating under reduced pressure after the ethanol extract that step b is made filters and get medicinal extract, for subsequent use;
D, extraction: the medicinal extract that step c is made is suspended in the water, extracts with sherwood oil, ethyl acetate and propyl carbinol successively, removes solvent again, gets respectively sherwood oil, ethyl acetate and n-butyl alcohol extract, and is for subsequent use;
E, separation: the acetic acid ethyl ester extract that steps d is made is through 100 ~ 300 order silica gel column chromatographies, petroleum ether-ethyl acetate gradient elution with volume ratio 20:1,10:1,5:1,2:1,1:1,0:1 obtains Fr.1 ~ Fr.6 totally 6 components, Fr.3 is through silica gel column chromatography, chloroform with volume ratio 98:2,95:5,90:10: methyl alcohol gradient elution, obtain component Fr.3A～3C, Fr.3C is through silica gel column chromatography, chloroform with volume ratio 80:20: the acetone wash-out obtains formula (I) compound through Sephadex LH-20 column chromatography methyl alcohol purifying again.
3. a kind of flavanols compounds according to claim 1 is characterized in that: the application of described flavanols compounds in preparing prevention or treatment human cervical carcinoma, people's chronic myelogenous leukemia, human acute myeloid leukemia medicine.
4. a kind of flavanols compounds according to claim 1 is characterized in that: described flavanols compounds prevent the underwater structure surface be subject to halobiontic adhere to and/or stained aspect application.
5. a kind of flavanols compounds according to claim 1 is characterized in that: described flavanols compounds prevent that marine organisms from adhering to and/or stained aspect application.
6. a kind of flavanols compounds according to claim 5 is characterized in that: described marine organisms are that the barnacle class is biological.
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| CN108484628A (en) * | 2018-05-25 | 2018-09-04 | 广西中医药大学 | Application of the kusulactone class compound in preventing marine biofouling |
| CN110372656A (en) * | 2019-07-22 | 2019-10-25 | 沈阳药科大学 | Flavanols Tiopronin derivative and its preparation method and application |
| CN112961137A (en) * | 2021-02-26 | 2021-06-15 | 沈阳药科大学 | Flavan-3,4-diol derivative and extraction method and application thereof |
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| CN108017609A (en) * | 2017-12-11 | 2018-05-11 | 武汉华益通生物科技有限公司 | A kind of flavanoid monomeric compound and its preparation method and application |
| CN108017609B (en) * | 2017-12-11 | 2020-04-10 | 武汉华益通生物科技有限公司 | Flavane monomer compound and preparation method and application thereof |
| CN108484628A (en) * | 2018-05-25 | 2018-09-04 | 广西中医药大学 | Application of the kusulactone class compound in preventing marine biofouling |
| CN108484628B (en) * | 2018-05-25 | 2020-01-17 | 广西中医药大学 | Application of quassin lactone compounds in preventing marine biofouling |
| CN110372656A (en) * | 2019-07-22 | 2019-10-25 | 沈阳药科大学 | Flavanols Tiopronin derivative and its preparation method and application |
| CN110372656B (en) * | 2019-07-22 | 2022-04-05 | 沈阳药科大学 | Flavanol tiopronin derivative and its preparing method and use |
| CN112961137A (en) * | 2021-02-26 | 2021-06-15 | 沈阳药科大学 | Flavan-3,4-diol derivative and extraction method and application thereof |
| CN112961137B (en) * | 2021-02-26 | 2022-08-12 | 沈阳药科大学 | Flavan-3,4-diol derivative and extraction method and application thereof |
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