CN101497593A - 5-hydroxy coumarin and pyranoid type coumarin compounds, synthesizing method and use - Google Patents
5-hydroxy coumarin and pyranoid type coumarin compounds, synthesizing method and use Download PDFInfo
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Abstract
The invention relates to a compound of 5-hydroxycoumarin and pyranocoumarin and synthesis and application thereof. The compound has a structural formula I or II; during preparation, according to the mol portion, under the catalytic action of 2 to 6 portions of SO2-OSO3H(silicon sulfonic acid), 1 to 3 portions of 5-iodine-1 and 3-dihydroxyhenzene and 1 to 3 portions of RCOCH2COOCH2CH3 are condensed to obtain the compound of which the structural formula is iodo-5-hydroxycoumarin; 1 to 4 portions of compound of iodo-5-hydroxycoumarin and 2 to 8 portions of 3-methyl-2-crotonaldehyde or 3-chloro-3-methylbutyne are reacted to generate a compound of iodo-pyranocoumarin; and finally, by coupled reaction, the coumarin compound with the structural formula I or II is generated. The IC50 value of the compound on breast cancer cells MCF-7 reaches 3.3 to 18.3, so that the compound can strongly inhibit the breast cancer cells MCF-7.
Description
Technical field
The present invention relates to 5-Hydroxycoumarin and pyranocoumarin derivative, this compounds has the effect of MCF-7 cell inhibiting, and wherein some has the obvious suppression effect, can be used for preparing guide's thing for the treatment of breast cancer medicines.
Technical background
Coumarin kind compound is distributed widely in the middle of the plant, (as Calanolide A was a kind of natural product that belongs to tropical plants from multiple U.S. leaf in the middle of the coumarin ring system appeared at natural product, be concentrated in Phloroglucinol core tonka bean camphor on every side, chromanane and chromene ring system, be a kind of strong inhibitor of human immunodeficiency virus-1 reversed transcriptive enzyme) exist special pharmacological property usually, excited chemist and Pharmaceutical Chemist to explore natural tonka bean camphor or its synthetic analogues interest greatly as medicinal application.Many based on each analog derivative of coumarin ring system synthetic, as furocoumarin(e), pyranocoumarin, amidosulfonic acid class tonka bean camphor, in photochemotherapy, antitumor, anti AIDS virus, central nervous system stimulant, antibiotic, anti-inflammatory has vital role (Kennedy, K.O. on the anticoagulation; Thornes, R.D.Coumarins:Biology, Applications and Mode of Action, Wiley, Chichester, 1997.).In fact, coumarin kind compound has wide biological activity like this, so that has the people to be referred to as " a many-side people pharmaceutically " (CN1450062A).
Particularly aspect the chemotherapy of mammary cancer, some Hydroxycoumarins and pyranoid type coumarin compounds have the inhibition activity of sulfatase and aromatizing enzyme, simultaneously some Hydroxycoumarin analogues also can be used as selective estrogen receptor modulators and become with the oestrogenic hormon binding substances as potential anti-breast cancer reagent (Musa, M.A.; Cooperwood, J.S.; Khan, M.O.F.Current Medicinal Chemistry, 2008,15 (26), 2664-2667).Yet more naturally occurring tonka bean camphors have certain effect at anticancer aspect, cause liver poisoning but often follow.Therefore with natural tonka bean camphor relatively, the synthetic coumarin compound can provide safer analogue, the treatment factor of stronger drug effect and Geng Gao.Mammary cancer is postmenopausal women's a kind of multiple cancer simultaneously.According to statistics, by the end of 2005, the whole world had 50.2 ten thousand people to die from mammary cancer.Thereby a synthetic class can be used to prevent and the potential coumarins medicine for the treatment of mammary cancer seems very necessary.
Summary of the invention
The purpose of this invention is to provide 5-Hydroxycoumarin and pyranoid type coumarin compounds that a class has obvious anti-breast cancer cell MCF-7;
Another object of the present invention is to provide the synthetic method of a class 5-Hydroxycoumarin and pyranoid type coumarin compounds.
The application that also has a purpose to provide a class 5-Hydroxycoumarin and pyranoid type coumarin compounds of the present invention.
Coumarins derivative involved in the present invention, the novel structure uniqueness has stronger anti-breast cancer cell MCF-7 effect through the part of determination of activity in them, can be used for preparing guide's thing for the treatment of breast cancer medicines.
Purpose of the present invention is achieved through the following technical solutions:
5-Hydroxycoumarin and pyranoid type coumarin compounds is characterized in that having following structural formula:
Wherein R is methyl, propyl group or phenyl; Q is selected from a kind of among following Q1～Q5;
In structural formula I, when R is a methyl, Q=Q
1When R is a propyl group, Q=Q
1, Q
2Or Q
3When R is a phenyl, Q=Q
1, Q
2Or Q
3
In structural formula II, when R is a methyl, Q=Q
1, Q
2, Q
4Or Q
5When R is a propyl group, Q=Q
1, Q
2, Q
3, Q
4Or Q
5When R is a phenyl, Q=Q
1, Q
2, Q
3, Q
4Or Q
5
For further realizing the object of the invention, described compound in structural formula I is following structural formula 1,2,3,7,8,9 or 10; The compound of described structural formula II is a kind of in the following structural formula 4～6,11～21.
The synthetic method of described 5-Hydroxycoumarin and pyranoid type coumarin compounds comprises the steps: (1) in molfraction, with the 5-iodo-1 of 1-3 part, the 3-dihydroxy-benzene through with the RCOCH of 1-3 part
2COOCH
2CH
3SO 2-6 part
2-OSO
3Being condensed into structural formula under H (silicon sulfonic acid) catalysis is
Iodo 5-Hydroxycoumarin compounds;
(2) in molfraction, the iodo 5-Hydroxycoumarin compounds of 1-4 part with the 3-methyl-2-butene aldehyde of 2-8 part or 3-chloro-3-methyl butine reaction generating structure formula is again
The iodo samidin;
(3) in molfraction, iodo 5-Hydroxycoumarin compounds or iodo samidin with 1-2 part are substrate, with 1 of 0.1-0.2 part, 1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture is a catalyzer, in the presence of the cesium fluoride or Potassium monofluoride of organic solvent and 1-3 part, under the temperature of 60-80 degree, with the 2-thionaphthene boric acid or the 1-thianthrene boric acid of 2-4 part, 4-(4-borono-anilino)-4-acyl butyric acid or 4 methylsulfonyl amido phenylo boric acid generation coupled reaction generating structure formulas are the coumarin kind compound of I or II.
The application in the preparation anti-breast cancer medicines of described 5-Hydroxycoumarin and pyranoid type coumarin compounds.
Method of the present invention can be represented by following type reaction formula:
Synthetic method of the present invention is not only easy, and this compounds has the effect of stronger anti-breast cancer cell MCF-7, for anti-breast cancer medicines provides screening.
Compared with prior art, the present invention has following advantage or effect:
(1) coumarins derivative involved in the present invention, its synthesis step is few, and the method maturation is purified easily, productive rate height, environmental friendliness (as the use of the environmentally friendly catalyzer silicon sulfonic acid of environmentally safe); With natural tonka bean camphor relatively, such coumarin compound can provide safer analogue, stronger drug effect and the treatment factor of Geng Gao, for efficient anti-breast cancer medicines provides screening.
(2) coumarins derivative involved in the present invention, biological activity determination shows that they have stronger restraining effect to breast cancer cell MCF-7, wherein a part has strong restraining effect, as the IC of 17 couples of breast cancer cell MCF-7 of compound
50Value has reached 3.3 μ M, is guide's thing of potential anti-breast cancer medicines.
Embodiment
For better understanding the present invention, the present invention is described in further detail below in conjunction with embodiment, but the scope of protection of present invention is not limited to the scope that embodiment represents.
The preparation of embodiment 1 compound 1
In flask at the bottom of an amount of volumetrical garden, add 5-iodo-1,3-dihydroxy-benzene 0.52 gram, methyl aceto acetate 0.28 gram, silicon sulfonic acid (SO
2-OSO
3H) 0.9 gram (is equal to 2.3mmol H
+), and add 10 milliliters of methylene dichloride, refluxed 6 hours.After reacting completely, with the dissolve with ethanol of heat and remove by filter silicon sulfonic acid, ethyl alcohol recrystallization obtains white crystal compound 1, productive rate 94.1%, and fusing point: 262 ° of C decompose, mass spectrum (APCI-MS): 302.6 (calculated values: 302.07).
The preparation of embodiment 2 compounds 2
In flask at the bottom of an amount of volumetrical garden, add 5-iodo-1,3-dihydroxy-benzene 1.18 grams, ethyl butyrylacetate 0.79 gram, silicon sulfonic acid (SO
2-OSO
3H) 1.9 grams (are equal to 4.8mmol H
+), and add 10 milliliters of methylene dichloride, refluxed 6 hours.After reacting completely, with heat dissolve with ethanol and remove by filter silicon sulfonic acid, ethyl alcohol recrystallization obtains white crystal compound 2, productive rate: 90.2%, fusing point: 232-233 ℃, mass spectrum (APCI-MS): 330.7 (calculated values: 330.7).
The preparation of embodiment 3 compounds 3
In flask at the bottom of an amount of volumetrical garden, add 5-iodo-1,3-dihydroxy-benzene 1.18 grams, ethyl benzoylacetate 0.96 gram, silicon sulfonic acid (SO
2-OSO
3H) 1.9 grams (are equal to 4.8mmol H
+), and add 10 milliliters of methylene dichloride, refluxed 8 hours.After reacting completely, with the dissolve with ethanol of heat and remove by filter silicon sulfonic acid, ethyl alcohol recrystallization obtains light yellow crystal compound 3, productive rate: 89.0%, and fusing point: 240-241 ℃, mass spectrum (ESI-MS): 362.8[M-H]
+(calculated value: 364.13).
The preparation of embodiment 4 compounds 4
In round-bottomed flask, add compound 30.22 grams, 3-methyl-2-butene aldehyde 0.4 gram, phenyl-boron dihydroxide 0.45 gram, 5 milliliters of propionic acid, 40 milliliters of toluene, and load onto water trap, reflux condensing tube, refluxed 8 hours, after reacting completely, ethyl acetate extraction, saturated common salt water washing, drying, the silica gel column chromatography separation obtains faint yellow solid compound 4, productive rate 79.2%.Fusing point: 198-199 ℃, mass spectrum (APCI-MS): 430.7 (calculated values: 430.2).
The preparation of embodiment 5 compounds 5
In round-bottomed flask, add compound 2,0.20 grams, 3-methyl-2-butene aldehyde 0.4 gram, phenyl-boron dihydroxide 0.45 gram, 5 milliliters of propionic acid, 40 milliliters of toluene, and load onto water trap, reflux condensing tube, refluxed 8 hours, after reacting completely, ethyl acetate extraction, saturated common salt water washing, drying, the silica gel column chromatography separation obtains white solid compound 5, productive rate: 81.2%, fusing point: 174-175 ℃, mass spectrum (APCI-MS): 397.0 (calculated values: 396.2).
The preparation of embodiment 6 compounds 6
In round-bottomed flask, add compound 1,0.18 gram, 3-methyl-2-butene aldehyde 0.35 gram, phenyl-boron dihydroxide 0.40 gram, 5 milliliters of propionic acid, 40 milliliters of toluene, and load onto water trap, reflux condensing tube, refluxed 8 hours, after reacting completely, ethyl acetate extraction, saturated common salt water washing, drying, the silica gel column chromatography separation obtains white solid compound 6, productive rate: 82.1%, fusing point: 133-134 ℃, mass spectrum (APCI-MS): 368.7 (calculated values: 368.2).
The preparation of embodiment 7 compounds 7
Compound 3,0.09 grams, benzothienyl-2-boric acid 0.18 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.01 gram, cesium fluoride 0.15 gram is dissolved in 4 milliliters of N, N-two basic methane amides (DMF) together, in ar gas environment, temperature 80 degree heated 24 hours down, after reacting completely, added an amount of distilled water, ethyl acetate extraction, drying, silica gel column chromatography obtains yellow solid compound 7.Productive rate 82.1%, fusing point: 251-253 ℃, high resolution mass spectrum (HRAPCI-MS) 370.0667, calculated value 370.0664.
The preparation of embodiment 8 compounds 8
Compound 3,0.09 grams, 1-thianthrene boric acid 0.26 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.01 gram, cesium fluoride 0.15 gram is dissolved in 4 milliliters of N, N-two basic methane amides (DMF) together, in ar gas environment, temperature 80 degree heated 24 hours down, after reacting completely, added an amount of distilled water, ethyl acetate extraction, drying, silica gel column chromatography obtains light yellow solid compound 8.Productive rate: 81.2%, fusing point: 292-294 ℃; High resolution mass spectrum (HRAPCI-MS) 452.0543, calculated value 452.0541.
The preparation of embodiment 9 compounds 9
Compound 2,0.08 grams, benzothienyl-2-boric acid 0.17 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.01 gram, cesium fluoride 0.12 gram is dissolved in 4 milliliters of N together, N-two basic methane amides (DMF), in ar gas environment, temperature 80 degree heated 16 hours down, after reacting completely, add an amount of distilled water, ethyl acetate extraction, drying, silica gel column chromatography obtains light yellow solid compound 9, productive rate: 83.0%, fusing point: 282-283 ℃; High resolution mass spectrum (HRAPCI-MS) 336.0824, calculated value 336.0820.
The preparation of embodiment 10 compounds 10
Compound 2,0.08 grams, 1-thianthrene boric acid 0.26 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.01 gram, cesium fluoride 0.12 gram is dissolved in 4 milliliters of N together, N-two basic methane amides (DMF), in ar gas environment, temperature 80 degree heated 16 hours down, after reacting completely, add an amount of distilled water, ethyl acetate extraction, drying, silica gel column chromatography obtains shallow white solid compound 10, productive rate: 81.8%, fusing point: 264-265 ℃; High resolution mass spectrum (HRAPCI-MS) 418.0695, calculated value 418.0697.
The preparation of embodiment 11 compounds 11
Compound 4,0.108 grams, benzothienyl-2-boric acid 0.18 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.01 gram, cesium fluoride 0.15 gram is dissolved in 4 milliliters of N together, N-two basic methane amides (DMF), in ar gas environment, temperature 80 degree heated 24 hours down, after reacting completely, add an amount of distilled water, ethyl acetate extraction, drying, silica gel column chromatography obtains yellow solid compound 11, productive rate: 80.2%, fusing point: 210-211 ℃; High resolution mass spectrum (HRAPCI-MS) 436.1137, calculated value 436.1133.
The preparation of embodiment 12 compounds 12
Compound 4,0.108 grams, 1-thianthrene boric acid 0.26 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.015 gram, cesium fluoride 0.15 gram is dissolved in 4 milliliters of N together, N-two basic methane amides (DMF), in ar gas environment, temperature 80 degree heated 24 hours down, after reacting completely, add an amount of distilled water, ethyl acetate extraction, drying, silica gel column chromatography obtains light yellow solid compound 12, productive rate: 76.4%, fusing point: 217-219 ℃; High resolution mass spectrum (HRAPCI-MS) 518.1015, calculated value 518.1010.
The preparation of embodiment 13 compounds 13
Compound 5,0.1 grams, benzothienyl-2-boric acid 0.18 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.012 gram, cesium fluoride 0.15 gram is dissolved in 4 milliliters of N together, N-two basic methane amides (DMF), in ar gas environment, temperature 80 degree heated 24 hours down, after reacting completely, add an amount of distilled water, ethyl acetate extraction, drying, silica gel column chromatography obtains yellow solid compound 13, productive rate: 79.1%, fusing point: 148-149 ℃; High resolution mass spectrum (HRAPCI-MS) 402.1293, calculated value 402.1290.
The preparation of embodiment 14 compounds 14
Compound 5,0.1 grams, 1-thianthrene boric acid 0.26 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.012 gram, cesium fluoride 0.15 gram is dissolved in 4 milliliters of N together, N-two basic methane amides (DMF), in ar gas environment, temperature 80 degree heated 24 hours down, after reacting completely, add an amount of distilled water, ethyl acetate extraction, drying, silica gel column chromatography obtains white solid compound 14, productive rate: 81.1%, fusing point: 221-222 ℃; High resolution mass spectrum (HRAPCI-MS) 484.1169, calculated value 484.1167.
The preparation of embodiment 15 compounds 15
Compound 6,0.08 grams, benzothienyl-2-boric acid 0.18 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.01 gram, cesium fluoride 0.12 gram is dissolved in 4 milliliters of N together, N-two basic methane amides (DMF), in ar gas environment, temperature 80 degree heated 16 hours down, after reacting completely, add an amount of distilled water, ethyl acetate extraction, dry, silica gel column chromatography obtains light yellow solid compound 15, productive rate: 79.9%, and fusing point: 154-155 ℃, high resolution mass spectrum (HRAPCI-MS) 374.0979, calculated value 374.0977.
The preparation of embodiment 16 compounds 16
Compound 4,0.108 grams, 4-Toluidrin phenylo boric acid 0.215 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.02 gram, cesium fluoride 0.18 gram is dissolved in 4 milliliters of N together, N-two basic methane amides (DMF), in ar gas environment, temperature 80 degree heated 14 hours down, after reacting completely, add an amount of distilled water, ethyl acetate extraction, drying, silica gel column chromatography obtains pale yellow crystals compound 16, productive rate: 81.4%, fusing point: 160-161 ℃; High resolution mass spectrum (HRAPCI-MS) 473.1293, calculated value 473.1297.
The preparation of embodiment 17 compounds 17
Compound 5,0.09 grams, 4-Toluidrin phenylo boric acid 0.215 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.02 gram, cesium fluoride 0.18 gram is dissolved in 4 milliliters of N together, N-two basic methane amides (DMF), in ar gas environment, temperature 80 degree heated 16 hours down, after reacting completely, add an amount of distilled water, ethyl acetate extraction, drying, silica gel column chromatography obtains pale yellow crystals compound 17, productive rate: 78.6%, fusing point: 190-191 ℃; High resolution mass spectrum (HRAPCI-MS) 439.1451, calculated value 439.1453.
The preparation of embodiment 18 compounds 18
Compound 6,0.09 grams, benzothienyl-2-boric acid 0.215 gram, 1,1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture (dppf (PdCl
2)) 0.02 gram, cesium fluoride 0.18 gram is dissolved in 4 milliliters of N together, N-two basic methane amides (DMF), in ar gas environment, temperature 80 degree heated 16 hours down, after reacting completely, add an amount of distilled water, ethyl acetate extraction, drying, silica gel column chromatography obtains white solid compound 18, productive rate: 81.0%, fusing point: 236-237 ℃; High resolution mass spectrum (HRAPCI-MS) 411.1144, calculated value 411.1140.
Embodiment 19 coumarin derivativess are measured the restraining effect of breast cancer cell MCF-7
MTT (dimethylthiazole phenylbenzene Thiazolyl blue tetrazolium bromide salt) test: the MCF-7 cell inoculation in the vegetative period of taking the logarithm is on 96 orifice plates, and every hole cumulative volume is 100 μ L, places 37 ℃, 5% CO
2Cultivate in the incubator, treat cell attachment after, serum starvation 12h adds above-mentioned various given the test agent and makes its ultimate density be respectively 1,5,10,15,25,50,100 μ M, each concentration is established four parallel holes, sets up control group simultaneously; Drug effect 48h, it is the MTT solution 10 μ L of 5mg/mL that every hole adds mass concentration, after continuing to cultivate 4h, the nutrient solution that inclines adds 150 μ L DMSO, after vibration treats that formazan dissolves colour developing fully, measure absorbancy (A) value with enzyme connection instrument with the 490nm wavelength, calculate inhibitory rate of cell growth.
And the drug level that adopts improvement bandit formula method calculating inhibiting rate to reach at 50% o'clock is IC
50Value.To the inhibition determination of activity of breast cancer cell MCF-7, result such as table one.Each compound is to the IC of breast cancer cell MCF-7 in the table 1
50Value, (numerical value is with " mean value ± standard deviation " expression, concentration unit μ M)
Table 1
Illustrate: compound number and pairing structural formula are with reference to claim 1 and 2; Active testing is independently finished three times.
The explanation of last table 1: each compound has in various degree restraining effect to breast cancer cell MCF-7.Wherein compound 1,5, the IC of 7,8,10,12,16,17,18 couples of breast cancer cell MCF-7
50Value has reached 18.3,13.7,7.6,14.2 respectively, and 14.4,7.2,5.3,3.3,6.5 μ M illustrate that these compounds have stronger breast cancer cell MCF-7 restraining effect, are the potential drugs of anti-breast cancer.
Claims (4)
1,5-Hydroxycoumarin and pyranoid type coumarin compounds is characterized in that having following structural formula:
Wherein R is methyl, propyl group or phenyl; Q is selected from following Q
1～Q
5In a kind of;
In structural formula I, when R is a methyl, Q=Q
1When R is a propyl group, Q=Q
1, Q
2Or Q
3When R is a phenyl, Q=Q
1, Q
2Or Q
3
In structural formula II, when R is a methyl, Q=Q
1, Q
2, Q
4Or Q
5When R is a propyl group, Q=Q
1, Q
2, Q
3, Q
4Or Q
5When R is a phenyl, Q=Q
1, Q
2, Q
3, Q
4Or Q
5
2,5-Hydroxycoumarin according to claim 1 and pyranoid type coumarin compounds is characterized in that described compound in structural formula I is following structural formula 1,2,3,7,8,9 or 10; The compound of described structural formula II is a kind of in the following structural formula 4～6,11～21.
3, the synthetic method of described 5-Hydroxycoumarin of claim 1 and pyranoid type coumarin compounds is characterized in that comprising the steps:
(1) in molfraction, with the 5-iodo-1 of 1-3 part, the 3-dihydroxy-benzene through with the RCOCH of 1-3 part
2COOCH
2CH
3SO 2-6 part
2-OSO
3Being condensed into structural formula under H (silicon sulfonic acid) catalysis is
Iodo 5-Hydroxycoumarin compounds;
(2) in molfraction, the iodo 5-Hydroxycoumarin compounds of 1-4 part with the 3-methyl-2-butene aldehyde of 2-8 part or 3-chloro-3-methyl butine reaction generating structure formula is again
The iodo samidin;
(3) in molfraction, iodo 5-Hydroxycoumarin compounds or iodo samidin with 1-2 part are substrate, with 1 of 0.1-0.2 part, 1 '-two (diphenyl phosphine) ferrocene palladium chloride (II) methylene dichloride mixture is a catalyzer, in the presence of the cesium fluoride or Potassium monofluoride of organic solvent and 1-3 part, under the temperature of 60-80 degree, with the 2-thionaphthene boric acid or the 1-thianthrene boric acid of 2-4 part, 4-(4-borono-anilino)-4-acyl butyric acid or 4-methylsulfonyl amido phenylo boric acid generation coupled reaction generating structure formula are the coumarin kind compound of I or II.
4, the application in the preparation anti-breast cancer medicines of described 5-Hydroxycoumarin of claim 1 and pyranoid type coumarin compounds.
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| HRP960308A2 (en) * | 1996-07-02 | 1998-08-31 | Ljerka Poljak | New coumarine derivatives, process for the preparation thereof and their use |
| GB9920912D0 (en) * | 1999-09-03 | 1999-11-10 | Indena Spa | Novel derivatives of flavones,xanthones and coumarins |
| CN1281599C (en) * | 2003-05-15 | 2006-10-25 | 中国科学院上海有机化学研究所 | Coumarin group compound, synthesis process and use thereof |
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| CN102336763B (en) * | 2011-08-17 | 2013-11-13 | 浙江工业大学 | Synthesis method for pyranocoumarin derivatives |
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| CN106279083B (en) * | 2016-08-02 | 2019-01-08 | 浙江大学 | A kind of furocoumarin analog derivative and preparation method thereof |
| CN107915704A (en) * | 2016-10-10 | 2018-04-17 | 北京工商大学 | A kind of synthetic method of simple coumarin kind compound |
| CN112062773A (en) * | 2019-06-11 | 2020-12-11 | 中国科学院大连化学物理研究所 | Method for acid-catalyzed cyclization reaction of 4-hydroxycoumarin and isoprene |
| CN112540143A (en) * | 2019-09-23 | 2021-03-23 | 华南理工大学 | Aryl sulfatase inhibitor and preparation method and application thereof |
| CN111620912A (en) * | 2020-06-28 | 2020-09-04 | 南宁师范大学 | Semi-sandwich type metal complex containing coumarin ligand, preparation method and application |
| CN111620912B (en) * | 2020-06-28 | 2022-11-18 | 南宁师范大学 | Semi-sandwich type metal complex containing coumarin ligand, preparation method and application |
| CN112042680A (en) * | 2020-09-14 | 2020-12-08 | 何述安 | Environment-friendly preservative and preparation method thereof |
| CN112042680B (en) * | 2020-09-14 | 2022-06-21 | 何述安 | Environment-friendly preservative and preparation method thereof |
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