CN101856351B - Composition and use thereof in preparation of RXR receptor transcription inhibitor - Google Patents
Composition and use thereof in preparation of RXR receptor transcription inhibitor Download PDFInfo
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Abstract
The invention discloses a composition and use thereof in the preparation of an RXR receptor transcription inhibitor, which belong to the field of medicaments and foods. The composition serving as the RXR receptor transcription inhibitor can be used in the preparation of foods or medicaments for preventing or treating cardiovascular diseases, cancers or diabetes and can be formed into powder, tablets, capsules, pills, suppositories, drops, enteric coated preparations, injections, syrups, emulsion, suspensions, tinctures, paste or spray. The composition and the use thereof are based on a mechanism that: RXR may be an ideal molecular target spot for screening antineoplastic agents; and the finding and development of compounds with selective RXR regulation approaches or medical compositions with the advanced characteristic have practical significance.
Description
Technical field
The invention belongs to pharmaceuticals and field of food, particularly a kind of compositions and the application in preparation rxr receptor transcription inhibitor thereof.
Background technology
Nuclear receptor is member maximum in the eukaryotic cell transcription factor family, almost participates in regulating all physiological process of cell through regulating target gene expression, comprises growth, propagation, differentiation, metabolism, apoptosis, immunity etc.All nuclear receptors all comprise three districts: the N petiolarea of length variations, the DNA land (DBD) of high conservative and ligand binding domain (LBD), wherein LBD for nuclear receptor dimerization and nuclear receptor and auxilliary activator or co-repressor to combine all be necessary.Steroid hormone; Retinol; Hormones such as thyroxin and vitamin D part changes the conformation of the ligand binding domain (LBD) of nuclear receptor and influences the Dimerized of nuclear receptor, Dimerized be nuclear receptor activation, carry out that effective DNA combines and the important foundation of transcriptional regulatory; After auxilliary activator and nuclear receptor combine its conformation is become and be easier to combine with DNA, co-repressor then acts on the contrary.
Because numerous functions of nuclear receptor regulating cell; Its expression or regulation and control are unusual closely related with human numerous disease such as cardiovascular disease, cancer, diabetes etc.; And nuclear receptor adjustable particular target gene transcription after respective ligand or micromolecular compound are induced is active and produce different biological effects, so nuclear receptor is the molecular target of the drug screening making us attracting.
In more than 150 nuclear receptor family members, retinol X receptor (RXR) is all very unique on 26S Proteasome Structure and Function.In mammal and other biology, have two types retinol receptor, called after retinoic acid receptors (RAR) and retinol X receptor (RXR) include α, three kinds of hypotypes of beta, gamma respectively.As transcription factor, RAR and RXR combine through forming RXR/RAR heterodimer and RXR/RXR homodimer and DNA response element (REs) in nucleus, take place the embryo, play a significant role in cell proliferation, differentiation, the apoptosis.Can only take place Dimerized different with RXRs with RARs; Many members in RXRs ability and the steroid hormone receptor superfamily are taken place Dimerized, comprise peroxisome Proliferator-activated receptor (PPAR), Thyroid Hormone Receptors (TR); Vitamin D receptor (VDR) and several kinds of orphan receptors; Like liver X receptor (LXR), embryo X receptor (PXR), sustained activation receptor (CAR) and TR3/Nur77/NGFI-B etc.Therefore, RXRs is combined in a large amount of nuclear hormone signal pathways of regulation and control through formation heterodimer and target gene and is playing the part of important role.
What accepted by people now is that retinoid chemical compound or the chemical compound that contains retinoid active substance combination can be used for treating numerous disease or extenuate pathological symptom.The retinoid chemical compound has type ii diabetes, hyperlipidemia and arteriosclerosis etc. in order to treatment apoptosis disease not normal or metabolism disorder; Cancer in order to prevention and treatment has breast carcinoma, skin carcinoma, carcinoma of prostate, cervical cancer, uterus carcinoma, colon cancer, bladder cancer, esophageal carcinoma, gastric cancer, pulmonary carcinoma, laryngeal carcinoma, oral cancer, leukemia, lymphoma, Kaposi sarcoma etc.
Because selectively acting is in the RXR of RXR signal transduction pathway ligand compound; Reducing owing to have clear superiority aspect the toxic and side effects that causes with other acceptor interactions; Therefore RXR possibly be an ideal molecular target of screening antineoplastic drugs, discovers and develops the chemical compound with selective regulation RXR approach or has the drug regimen of these advanced treatment characteristics to have realistic meanings.The RXR selective agonist has received common concern in recent years, like Targretin (SR11247), LG100298,11246 etc.
Summary of the invention
In order to solve deficiency and the shortcoming that above-mentioned prior art exists, primary and foremost purpose of the present invention is to provide a kind of two benzene pyrrones compound compositions that comprised.
Another purpose of the present invention is to provide the purposes of above-mentioned composition as preparation rxr receptor transcription inhibitor.
The object of the invention is realized through following technical proposals: a kind of compositions, said composition comprise the two benzene pyrrones chemical compounds that have suc as formula (I) said structure:
R wherein
1Be OH, R
2Be H, substituted radical G or substituted radical I, R
3Be H, OH or OCH
3, R
4Be H, OH, OCH
3, substituted radical I, substituted radical J, substituted radical K or substituted radical L, and at R
2And R
3Between connect substituted radical C, substituted radical D or substituted radical E, R
3And R
4Between connect substituted radical A, substituted radical B or substituted radical F, R
5Be H, OH, OCH
3Or substituted radical K, R
6Be H or OH, R
7Be H, OH or OCH
3, R
8Be H, OCH
3, substituted radical H or substituted radical I,
Said pair of benzene pyrrones chemical compound contains 1,5-dihydroxy-4 ', 4 '-dimethyl-6 '-hydroxyl-4 ', 5 '-dihydropyran [2 ', 3 ': 3; 4]-and two benzene pyrrones (CC-1 is shown in 1), 1,6-dihydroxy-5-methoxyl group-4 ', 4 '-dimethyl-4,5-dihydropyran-6 '-ketone-[2 '; 3 ': 3,4]-two benzene pyrrones (CC-2 is shown in 2), 1,3,7-trihydroxy-2-(3-methyl butyl-2-alkene)-4-(7-methoxyl group-3; 7-dimethyl octyl group-2, the 5-diene)-two benzene pyrrones (CC-3 is shown in 3), 1,7-dihydroxy-4-(3; 7-dimethyl octyl group-2, the 6-diene)-5 '-(1-hydroxyl-1-Methylethyl)-4 ', 5 '-dihydrofuran [2 ', 3 ': 3; 2]-two benzene pyrrones (CC-4 is shown in 4), cattle wood ketone A (CC-5 is shown in 5), 1,6; 7-trihydroxy-2-(3-methyl butyl-2-alkene)-3-methoxyl group-8-(3-hydroxyl-3-methoxyl group butyl)-two benzene pyrrones (CF-1 is shown in 6) and 1,3,6; In 7-tetrahydroxy-2-(3-methyl butyl-2-alkene)-4-(3,7-dimethyl octyl group-2,6-diene)-two benzene pyrrones (CF-2 is shown in 7) more than one.
The method for preparing of said pair of benzene pyrrones chemical compound is by following operating procedure: the dry stem of Guttiferae cattle fogfruit cattle wood (Cratoxylum cochinchinense) or red bud wood (Cratoxylum formosum subsp.pruniflorum) is ground into coarse powder; Immerse to extract in the solvent cold extraction or heating and refluxing extraction in extracting solvent; Filter or the centrifugal insoluble matter of removing; Again gained is extracted solution and carry out concentrating under reduced pressure, separate obtaining two benzene pyrrones chemical compounds suc as formula (I) said structure.
Said extraction solvent is that volume fraction is 60% ethanol; Said method for distilling is a reflux, extract,, and said extraction time is 6 hours; Said separation is to adopt chromatography method and/or extraction to separate.
The quality percentage composition of two benzene pyrrones chemical compounds is 3.3-16.7% in the said compositions.
The application of above-mentioned compositions in preparation rxr receptor transcription inhibitor.
Above-mentioned compositions is applied to prepare the food or the pharmaceuticals of prevention or treatment cardiovascular disease, cancer or diabetes as the rxr receptor transcription inhibitor.
Said inhibition rxr receptor transcription inhibitor and pharmaceutically acceptable carrier are mixed and made into powder, tablet, capsule, pill, suppository, drop pill, enteric agents, injection, syrup, Emulsion, suspensoid, tincture, unguentum or spray.
The relative prior art of the present invention; Have following advantage and beneficial effect: the invention provides a kind of two benzene pyrrones compound compositions that comprised; Said composition has the rxr receptor transcripting suppressioning action; Can be used as the inhibitor that rxr receptor is transcribed; And can be used for preparing food or the pharmaceuticals that prevent or treat cardiovascular disease, cancer or diabetes, or truly have the chemical compound of associated uses, extract to mix above-mentioned composition and other, be used to prepare the food or the pharmaceuticals of prevention or treatment cardiovascular disease, cancer or diabetes.
Description of drawings
Fig. 1 is the transcriptional activity figure of the RXR α of Compound C C-1 and CC-6～CC-11 (10 μ M).
Fig. 2 is the transcriptional activity figure of the RXR α of Compound C C-2～CC-5 (10 μ M).
Fig. 3 is Compound C F-1, CF-4, the transcriptional activity figure of the RXR α of CF-5 and CF-8～CF-10 (10 μ M).
Fig. 4 is Compound C F-2, CF-3, CF-6, CF-7, the transcriptional activity figure of the RXR α of CF-11 and CF-12 (10 μ M).
Fig. 5 is the transcriptional activity figure of the RXR α of Compound C C-1 and CC-6 (1,5,20 μ M).
Fig. 6 is the transcriptional activity figure of the RXR α of Compound C C-2 (1,5,20 μ M).
Fig. 7 is the transcriptional activity figure of the RXR α of Compound C F-5 (10,20,40 μ M).
The specific embodiment
Below in conjunction with embodiment and accompanying drawing, the present invention is done further detailed description, but embodiment of the present invention is not limited thereto.
Embodiment 1: the two benzene pyrrones chemical compounds of extraction separation from cattle wood
The dry stem (6Kg) of Guttiferae cattle fogfruit cattle wood (Cratoxylum cochinchinense) is with 60% (V/V) alcohol-water heating and refluxing extraction, concentrated extract; Adopt ethyl acetate and n-butyl alcohol to carry out equal-volume extraction 3 times respectively; Ethyl acetate extraction part, promptly (CC is 142.5g) through silica gel column chromatography at cattle wood total two benzene pyrrone positions; Cyclohexane extraction-acetone (98: 2～0: 100) gradient elution obtains 10 sub-fractions (Fr.1～Fr.10).From sub-fraction Fr.2 (95: 5 eluting parts, 1.9g), Fr.6 (85: 15 eluting parts; 6.6g); (8: 2 eluting parts are separated out crystallization respectively in 11.2g), after the filtration to Fr.7; In cyclohexane extraction-acetone, obtain Compound C C-10 (187mg), CC-1 (95.2mg) and CC-7 (9.2mg) through recrystallization.Sub-fraction Fr.4 (9: 1 eluting parts, 17.5g), Fr.5 (85: 15 eluting parts, 9.6g) with Fr.6 in insoluble matter recrystallization in methanol obtain Compound C C-8 (210mg), CC-9 (830mg) and CC-6 (145mg).Sub-fraction Fr.5 is through silicagel column mesolow chromatograph, cyclohexane extraction-ethyl acetate (5: 1) eluting, and recrystallization obtains Compound C C-2 (26mg) in cyclohexane extraction-ethyl acetate solution again.(9: 1 eluting parts, 14.7g) through silica gel mesolow column chromatography, (9: 1-7: 1) gradient elution obtains 9 sub-fractions (Fr.3-1～Fr.3-9) to cyclohexane extraction-acetone to sub-fraction Fr.3.(9: 1 eluting parts are separated out crystallization in 1.29g) to sub-fraction Fr.3-6, and recrystallization obtains Compound C C-5 (7mg) in chloroform-methanol solution, sub-fraction Fr.3-7 (7: 1 eluting parts; Separate out crystallization 630mg), obtain Compound C C-4 (67mg) after the filtration, filtrating is through Sephadex LH-20 column chromatography; Chloroform-methanol (1: 1) eluting, again through silica gel mesolow column chromatography, cyclohexane extraction-acetone eluting; And the HPLC purification, methanol-water (85: 15) eluting obtains Compound C C-11 (8.1mg).Sub-fraction Fr.3-9 (7: 1 eluting parts, 534mg) through Sephadex LH-20 column chromatography, chloroform-methanol (1: 1) eluting, again through the ODS column chromatography, the methanol-water gradient elution obtains Compound C C-3 (6.3mg).Through physicochemical constant and modern Wave Spectrum means (MS, NMR), in conjunction with the document related data, identified their structure, be shown in the following figure:
Annotate: have
*The person is a noval chemical compound.
Compound C C-1; Yellow powder;
(c 0.414, acetone).UV(CH
3OH)λ
max(logε)：366(3.45)，317(4.07)，247(4.39)，204(4.19)。IR (KBr) v
Max: 3422cm
-1There is hydroxyl to have 1651cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (negative) provides m/z 327 [M-H]
-, releasing compound molecular weight is 328.HR-TOF-MS provides m/z 351.0868 ([M+Na]
+, value of calculation is 351.0845), confirm that the compound molecule formula is C
18H
16O
6, calculating its degree of unsaturation is 11.
1H-NMR (400MHz, in acetone-d
6) show 14 hydrogen signals, in conjunction with the HSQC collection of illustrative plates, confirm wherein 1 association phenolic hydroxyl group hydrogen signal δ
H12.94 (1H, s), 4 fragrant hydrogen signal [δ
H7.66 (1H, dd, J=7.9,1.1Hz), 7.38 (1H, dd, J=7.9,1.1Hz), 7.25 (1H, t, J=7.9Hz), 6.16 (1H, s)], the methine hydrogen signal [δ of two oxygen of 1 company
H5.53 (1H, dd, J=8.0,2.0Hz)], 1 group of methylene hydrogen signal [δ
H2.01 (1H, dd, J=13.6,2.0Hz), 1.92 (1H, dd, J=13.6,2.0Hz)], 2 groups of methyl hydrogen signal [δ
H1.73 (3H, s), 1.62 (3H, s)].
13C-NMR (100MHz, in acetone-d
6) collection of illustrative plates shows 18 spectral lines altogether, can know in conjunction with DEPT135 and HSQC collection of illustrative plates to comprise 1 carbonyl carbon signal (δ
C182.0), 8 sp
2Hydridization quaternary carbon signal (δ
C162.0,161.5,156.6,147.3,146.2,122.2,110.5,105.0), wherein 4 is to connect oxygen quaternary carbon, 4 sp
2Hydridization tertiary carbon (δ
C124.8,120.8,116.0,100.0), the tertiary carbon signal (δ of two oxygen of 1 company
C93.9), 1 mesomethylene carbon signal (δ
C46.7), 1 quaternary carbon signal (δ
C32.7), 2 methyl carbon signal (δ
C29.0,28.9).Comprehensively
1H-NMR,
13C-NMR data, molecular formula and degree of unsaturation can infer that this chemical compound for two benzene pyrrones chemical compounds, contains three hydroxyls in the structure.
1In the H-NMR collection of illustrative plates, δ
H12.94 (1H s), has an association phenolic hydroxyl group, δ in the prompting structure
H7.66 (1H, dd, J=7.9,1.1Hz), 7.38 (1H, dd, J=7.9,1.1Hz), 7.25 (1H, t J=7.9Hz), show that a phenyl ring in the structure has the three hydrogen structures of company;
1H with
13Two methyl signals [δ in the C-NMR collection of illustrative plates
H1.73 (3H, s), 1.62 (3H, s), δ
C29.0,28.9], a quaternary carbon signal (δ
C32.7), a methylene signals [δ
H2.01 (1H, dd, J=13.6,2.0Hz), 1.92 (1H, dd, J=13.6,2.0Hz), δ
C46.7] and the methine signal [δ of two oxygen of a company
H5.53 (1H, dd, J=8.0,2.0Hz), δ
C93.9] combine a remaining degree of unsaturation can know in the structure to have one 4 ', 4 '-dimethyl-6 '-hydroxyl-4 ', 5 '-the dihydropyran ring.All relevant by two groups of methyl hydrogen signal δ 1.73 (H-7) in the HMBC spectrum with C-4 (δ 110.5) with δ 1.62 (H-8); The methine hydrogen signal δ 5.53 (H-6) that connects two oxygen is relevant with C-3 (δ 161.5), can confirm the dihydropyran ring and is combined on the C-3 and C-4 of pair benzene pyrrone parent nucleus.By association hydroxyl hydrogen signal δ 12.94 (1-OH) and C-1 (δ 162.0) in the HMBC spectrum, C-2 (δ 100.0) is relevant with C-9a (δ 105.0), can confirm that it is connected on the C-1.Relevant by following HMBC: δ
H6.16/C-1 (162.0), C-3 (161.5), C-4 (110.5); C-9a (105.0), 7.38/C-8 (116.0), C-10a (146.2); 7.25/C-8a (122.2), C-10a (146.2) and 7.66/C-6 (120.8), C-9 (182.0); C-10a (146.2) can infer that four fragrant hydrogen lay respectively at C-2, and C-6 is on C-7 and the C-8.Other has oxygen carbon δ 147.3 (C-5) of company to should be the hydroxyl replacement according to molecular formula.
Comprehensive HSQC and HMBC collection of illustrative plates have carried out belonging to (table 1) to the whole carbon signals and the hydrogen signal of this chemical compound.
Through the SciFinder network retrieval, do not find relevant report, show that this is new two benzene pyrrones chemical compounds, called after 1; 5-dihydroxy-4 ', 4 '-dimethyl-6 '-hydroxyl-4 ', 5 '-dihydropyran [2 '; 3 ': 3,4]-two benzene pyrrones, its structural formula is following:
Compound C C-2, pale yellow powder, the reaction of hydroxamic acid ferrum is positive, and lactonic ring is arranged in the prompting structure.
(c＝0.359，acetone)。UV(CH
3OH)λ
max(logε)：350(3.76)，313(4.05)，246(4.46)，206(4.20)。IR (KBr) v
Max: 3398cm
-1There is hydroxyl to have 1778cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 379 [M+Na]
+, ESI-MS (negative) provides m/z 355 [M-H]
-, releasing compound molecular weight is 356.HR-TOF-MS provides m/z 379.0811 ([M+Na]
+, value of calculation is 379.0794), confirm that the compound molecule formula is C
19H
16O
7, calculating its degree of unsaturation is 12.
1H-NMR (400MHz, in acetone-d
6) show 15 hydrogen signals, ins conjunction with the HSQC collection of illustrative plates, affirmation wherein 1 phenolic hydroxyl group hydrogen signal δ 13.25 (1H, s), 3 fragrant hydrogen signal [δ 7.84 (1H; D, J=8.7Hz), 7.07 (1H, d, J=8.7Hz); 6.39 (1H, s)], 1 group of methylene hydrogen signal [δ 2.83 (2H, s)]; 2 groups of methyl hydrogen signals [δ 1.69 (6H, s)], 1 group of methoxyl group hydrogen signal [δ 4.01 (3H, s)].
13C-NMR (100MHz, in acetone-d
6) collection of illustrative plates shows 18 spectral lines altogether, wherein can know to be the overlapping of two carbon signals from height for one, can know in conjunction with DEPT135 and HSQC collection of illustrative plates to comprise 2 carbonyl carbon signals (δ 182.0,166.9), 9 sp
2Hydridization quaternary carbon quaternary carbon signal (δ 162.8,158.1,157.9,155.4,151.8,135.9,114.7,110.8,106.3), wherein 6 is to connect oxygen quaternary carbon, 3 sp
2Hydridization tertiary carbon (δ 122.3,115.3,100.2), 1 mesomethylene carbon signal (δ 45.0), 1 quaternary carbon signal (δ 34.7), 2 methyl carbon signals [δ 28.0 (C * 2)], 1 methoxyl group carbon signal (δ 61.9).Comprehensively
1H-NMR,
13C-NMR data, molecular formula and degree of unsaturation can infer that this chemical compound for two benzene pyrrones chemical compounds, contains two hydroxyls, a methoxyl group in the structure.
1In the H-NMR collection of illustrative plates, (1H s), has an association phenolic hydroxyl group to δ 13.25 in the prompting structure, (J=8.7Hz), 7.07 (1H, d J=8.7Hz), show that there is the proton of a pair of ortho position coupling in a phenyl ring in the structure to δ 7.84 for 1H, d;
1H with
13Two methyl signals [δ in the C-NMR collection of illustrative plates
H1.69 (6H, s), δ
C28.0 (2C)], quaternary carbon signal (δ
C34.7), a methylene signals [δ
H2.83 (2H, s), δ
C45.0] and a lactone carbonyl (δ
C198.8) combine a remaining degree of unsaturation can know in the structure to have one 4 ', 4 '-dimethyl-4,5-dihydropyran-6 '-the ketone ring.All relevant by two groups of methyl hydrogen signal δ 1.69 (H-7 ' and H-8 ') in the HMBC spectrum with C-4 (110.8), can confirm the dihydro pyrone ring and be combined on the C-3 and C-4 of pair benzene pyrrone parent nucleus.By association hydroxyl hydrogen signal δ 13.25 (1-OH) and C-1 (162.8) in the HMBC spectrum, C-2 (100.2) is relevant with C-9a (106.3), can confirm that it is connected on the C-1.Relevant by following HMBC: δ
H4.01/C-5 (135.9), 6.39/C-1 (162.8), C-3 (158.1); C-4 (155.4), C-9a (106.3), 7.07/C-5 (135.9); C-8a (114.7) and 7.84/C-6 (157.9); C-9 (181.6) C-10a (151.8) can infer that a methoxyl group is connected on the C-5, and three fragrant hydrogen lay respectively at C-2, on C-7 and the C-8.Other has oxygen carbon δ 157.9 (C-6) of company to should be the hydroxyl replacement according to molecular formula.Comprehensive HSQC and HMBC collection of illustrative plates have carried out belonging to (table 1) to the whole carbon signals and the hydrogen signal of this chemical compound.Through the SciFinder network retrieval, do not find relevant report, show that this is new two benzene pyrrones chemical compounds, called after 1; 6-dihydroxy-5-methoxyl group-4 ', 4 '-dimethyl-4,5-dihydropyran-6 '-ketone-[2 '; 3 ': 3,4]-two benzene pyrrones, its structural formula is following:
Table 1 NMR data of CC-1and CC-2 (400MHz for
1H NMR, in acetone-d
6).
Compound C C-3; Brown powder;
(c 0.382, acetone).UV(CH
3OH)λ
max(logε)：377(3.64)，318(4.00)，257(4.36)，232(4.37)，203(4.41)。IR (KBr) v
Max3419cm
-1There is hydroxyl to have 1646cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 501 [M+Na]
+, ESI-MS (negative) provides m/z 477 [M-H]
-, releasing compound molecular weight is 478.HR-TOF-MS provides m/z 501.2260 ([M+Na]
+, value of calculation is 501.2253), confirm that the compound molecule formula is C
29H
34O
6, calculating its degree of unsaturation is 13.
1H-NMR (400MHz, in DMSO-d
6) show 32 hydrogen signals, ins conjunction with the HSQC collection of illustrative plates, affirmation wherein contain 1 association phenolic hydroxyl group hydrogen signal δ 13.15 (1H, s), 3 fragrant hydrogen signals [δ 7.40 (1H, d, J=3.0Hz), 7.39 (1H; D, J=9.0Hz), 7.26 (1H, dd, J=9.0,3.0Hz)], 2 alkene methine hydrogen signals [δ 5.22 (1H, brt; J=7.1Hz), δ 5.15 (1H, brt, J=6.9Hz)], and 2 trans alkene hydrogen signals [δ 5.43 (1H, dt, J=15.7,6.5Hz); δ 5.32 (1H, d, J=15.7Hz)], and 3 groups of methylene hydrogen signals [δ 3.49 (2H, d, J=7.1Hz), 3.31 (2H, d; J=6.9Hz), 2.64 (2H, d, J=6.5Hz)], and 5 groups of methyl hydrogen signals [δ 1.83 (3H, s), δ 1.73 (3H; S), δ 1.62 (3H, s), 1.08 (6H, s)], 1 group of methoxyl group hydrogen signal [δ 2.91 (3H, s)].
13C-NMR (100MHz, in DMSO-d
6) collection of illustrative plates shows 28 spectral lines altogether, wherein can know to be the overlapping of two carbon signals from height for one, can know in conjunction with DEPT135 and HSQC collection of illustrative plates to comprise 1 carbonyl carbon signal (δ 179.6), 11 sp
2Hydridization quaternary carbon signal (δ 161.7,157.4,153.6,152.6,148.9,133.0,130.4,120.1,110.2,105.8,101.6), wherein 5 is to connect oxygen quaternary carbon, 7 sp
2Hydridization tertiary carbon signal (δ 136.6,127.5, and 124.1,123.2,122.6; 118.7,107.9), 1 company's oxygen quaternary carbon signal (δ 74.0), (δ 41.8 for 3 mesomethylene carbon signals; 21.6,21.3), (δ 25.6,25.6 for 5 methyl carbon signals; 25.5,17.7,16.1), 1 methoxyl group carbon signal (δ 49.3).Comprehensively
1H-NMR,
13C-NMR data, molecular formula and degree of unsaturation can infer that this chemical compound for two benzene pyrrones chemical compounds, contains three hydroxyls in the structure.
1(1H, s 1-OH) locate to exist an association hydroxyl signal at δ 13.15 in the H-NMR collection of illustrative plates.δ 7.39 (1H, d, J=9.0Hz, H-5), 7.26 (1H, dd, J=9.0,3.0Hz is H-6) with 7.40 (J=3.0Hz H-8) locates three fragrant proton signals and shows that a phenyl ring in the structure has ABX coupling system for 1H, d.δ 7.39/C-7 in the HMBC spectrum, C-8a, 7.26/C-7, C-8, C-10a, 7.41/C-6, C-7, C-9, C-8a, C-10a relevant proved that they should belong to and has been H-5, H-6 and H-8.
1H with
13δ in the C-NMR collection of illustrative plates
H(3.31 2H, d, H-1 ')/δ
C(21.3 C-1 '), 5.15 (1H, brt, H-2 ')/122.6 (C-2 '), 1.62 (3H, s, H-4 ')/25.5 (C-4 '), 1.73 (3H, s, H-5 ')/17.7 (C-5 '), δ
C130.4 have an isopentene group in the signal indicating structure of (C-3 '), and according to H-1 ' and C-1 in the HMBC spectrum, it is connected the relevant deduction with C-3 of C-2 on the C-2.
1H with
13δ in the C-NMR collection of illustrative plates
H3.49 (2H, d, H-1 ")/δ
C21.6 (C-1 "), 5.22 (1H, brt, H-2 ")/123.2 (C-2 "), 2.64 (2H, d; H-4 ")/41.8 (C-4 "), 5.43 (2H, dt, H-5 ")/127.5 (C-5 "), 5.32 (1H, d; H-6 ")/136.6 (C-6 "), 1.08 (3H, s, H-8 ")/25.6 (C-8 "), 1.83 (3H, s; H-9 ")/16.1 (C-9 "), 1.08 (3H, s, H-10 ")/25.6 (C-10 "), δ
H2.91 (3H, s, 7 " OCH
3), δ
C133.0 (C-3 "), 74.0 (C-7 ")., 49.3 (7 " OCH
3) show in the structure and to have a 7-methoxyl group-3,7-dimethyl-octa-2,5-dialkylene substituent group.And based on H-1 in the HMBC spectrum " and C-3, it is connected the relevant deduction with C-4a of C-4 on the C-4.Locate be connected a hydroxyl according to chemical displacement value with molecular formula C-7 (153.6).
Comprehensive HSQC and HMBC collection of illustrative plates belong to the whole carbon signals and the hydrogen signal of this chemical compound.Through the SciFinder network retrieval, do not find relevant report, show that this is new two benzene pyrrones chemical compounds, called after 1,3,7-trihydroxy-2-(3-methyl butyl-2-alkene)-4-(7-methoxyl group-3,7-dimethyl octyl group-2,5-diene)-two benzene pyrrones,
1H-NMR with
13The C-NMR data are seen table 2, and its structural formula is following:
Compound C C-4; Yellow powder;
(c 0.568, acetone).UV (CH
3OH) λ
Max(log ε): 378 (3.68), 323 (4.08), 266 (4.40), 241 (4.36), 231 (4.39), 204 (4.38); IR (KBr) v
Max3283cm
-1There is hydroxyl to have 1668cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive), provide m/z487 [M+Na]
+, ESI-MS (negative) provides m/z 463 [M-H]
-, releasing compound molecular weight is 464.HR-TOF-MS provides m/z 487.2083 ([M+Na]
+, value of calculation is 487.2097), confirm that the compound molecule formula is C
28H
32O
6, calculating its degree of unsaturation is 13.
1H-NMR (400MHz, in DMSO-d
6) show 32 hydrogen signals, ins conjunction with the HSQC collection of illustrative plates, affirmation wherein contain 1 association close phenolic hydroxyl group hydrogen signal δ 12.96 (1H, s), 1 phenolic hydroxyl group hydrogen signal δ 9.91 (1H, s), 1 hydroxyl hydrogen signal δ 4.68 (1H; S), 3 fragrant hydrogen signals [δ 7.38 (1H, d, J=9.0Hz), 7.38 (1H, d, J=3.0Hz); 7.25 (1H, dd, J=9.0,3.0Hz)], and 2 alkene methine hydrogen signals [δ 5.20 (1H, brt), δ 4.94 (1H; Brt)], 1 oxygen methine hydrogen signal [δ 4.70 (1H, m)] even, 4 groups of methylene hydrogen signals [δ 3.30 (2H, m), 3.07 (2H, m); 1.95 (2H, m), 1.89 (2H, m)], and 5 groups of methyl hydrogen signals [δ 1.77 (3H, s), δ 1.46 (3H; S), δ 1.43 (3H, s), 1.17 (3H, s), δ 1.10 (3H, s)].
13C-NMR (100MHz, in DMSO-d
6) collection of illustrative plates shows 28 spectral lines altogether, can know in conjunction with DEPT135 and HSQC collection of illustrative plates to comprise 1 carbonyl carbon signal (δ 179.9), 11 sp
2Hydridization quaternary carbon signal (δ 165.4,154.7,154.2,153.8,148.9,134.6,130.5,120.0,107.1,102.7,101.1), wherein 5 is to connect oxygen quaternary carbon, 5 sp
2Hydridization tertiary carbon signal (δ 124.2,123.9,121.5,118.7,107.8); 1 oxygen quaternary carbon signal (δ 70.1) even, 1 oxygen tertiary carbon signal (δ 91.1) even, 4 mesomethylene carbon signals (δ 38.9,26.2, and 25.9; 21.4) 5 methyl carbon signals (δ 26.1,25.2,24.0,17.3,15.8).Comprehensively
1H-NMR,
13C-NMR data, molecular formula and degree of unsaturation can infer that this chemical compound for two benzene pyrrones chemical compounds, contains three hydroxyls in the structure.
1In the H-NMR collection of illustrative plates δ 12.96 (1H, s 1-OH) locate to exist an association hydroxyl signal, δ 9.91 (1H, s 7-OH) locate to exist a free phenolic hydroxyl group signal, δ 9.91/C-6 in the HMBC spectrum, C-7, the relevant of C-8 proved that it is connected on the C-7.δ 7.38 (1H, d, J=9.0Hz, H-5), 7.25 (1H, dd, J=9.0,3.0Hz is H-6) with 7.38 (J=3.0Hz H-8) locates three fragrant proton signals and shows that a phenyl ring in the structure has ABX coupling system for 1H, d.δ 7.38/C-6 in the HMBC spectrum, C-7, C-8a, C-10a, 7.25/C-7, C-8, C-10a, 7.38/C-6, C-7, C-9, C-8a, C-10a relevant proved that they should belong to and has been H-5, H-6 and H-8.
1H with
13δ in the C-NMR collection of illustrative plates
H(3.07 2H, m, H-4 ')/δ
C(26.2 C-4 '), 4.70 (1H, m, H-5 ')/91.1 (C-5 '), 1.17 (3H, s, H-7 ')/26.1 (C-7 '), 1.10 (3H, s, H-8 ')/24.0 (C-8 '), δ
C(70.1 C-6 '), δ
H4.68 (1H, s, 6 '-OH) show in the structure and to have one five carbon unit.Visible following relevant in the HMBC spectrum: H-4 '/C-2, C-6 ', H-5 '/C-3; H-7 '/C-5 ', C-6 ', C-8 '; H-8 '/C-5 ', C-6 ', C-7 ' and 6 '-OH/C-6 ' deducibility thus go out this five carbon unit and are one and are being connected the 1-hydroxyl-substituent dihydrofuran ring plate of 1-Methylethyl section; The dihydrofuran ring is connected on the C-2 and C-3 of two benzene pyrrone parent nucleus, and 1-hydroxyl-1-Methylethyl is connected on the C-2 ' of dihydropyran ring.
1H with
13δ in the C-NMR collection of illustrative plates
H3.30 (2H, m, H-1 ")/δ
C21.4 (C-1 "), 5.20 (1H, br t, H-2 ")/121.5 (C-2 "), 1.89 (2H, m; H-4 ")/38.9 (C-4 "), 1.95 (2H, m, H-5 ")/25.9 (C-5 "), 4.94 (1H, br t; H-6 ")/123.9 (C-6 "), 1.46 (3H, s, H-8 ")/25.2 (C-8 "), 1.77 (3H, s; H-9 ")/15.8 (C-9 "), 1.43 (3H, s, H-10 ")/17.3 (C-10 "), δ
C134.6 (C-3 "), 130.5 (C-7 ") shows in the structure and to have one 3,7-dimethyl-octa-2,6-dialkylene substituent group.And based on H-1 in the HMBC spectrum " and C-3, it is connected the relevant deduction with C-4a of C-4 on the C-4.Comprehensive HSQC and HMBC collection of illustrative plates belong to the whole carbon signals and the hydrogen signal of this chemical compound.Through the SciFinder network retrieval, do not find relevant report, show that this is new two benzene pyrrones chemical compounds, called after 1; 7-dihydroxy-4-(3,7-dimethyl octyl group-2,6-diene)-5 '-(1-hydroxyl-1-Methylethyl)-4 ', 5 '-dihydrofuran [2 '; 3 ': 3,2]-two benzene pyrrones
1H-NMR with
13The C-NMR data are seen table 2, and its structural formula is following:
Table 2.NMR data of CC-3and CC-4 (400MHz for
1H NMR, in DMSO-d
6)
Compound C C-5; Pale yellow powder;
(c 0.200, acetone).UV(CH
3OH)λ
max(logε)：377(3.68)，315(3.98)，286(4.33)，266(4.46)，230(4.33)，203(4.48)。IR (KBr) v
Max3420cm
-1There is hydroxyl to have 1624cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 479 [M+H]
+, ESI-MS (negative) provides m/z 477 [M-H]
-, releasing compound molecular weight is 478.HR-TOF-MS provides m/z 501.1901 ([M+Na]
+, value of calculation is 501.1889), confirm that the compound molecule formula is C
28H
30O
7, calculating its degree of unsaturation is 14.
1H-NMR (400MHz, in DMSO-d
6) show 30 hydrogen signals, ins conjunction with the HSQC collection of illustrative plates, affirmation wherein contain 1 association phenolic hydroxyl group hydrogen signal δ 13.32 (1H, s), 1 phenolic hydroxyl group hydrogen signal δ 10.01 (1H, s), 3 fragrant hydrogen signal [δ 7.45 (1H; D, J=9.0Hz), 7.39 (1H, d, J=3.0Hz), 7.30 (1H, dd; J=9.0,3.0Hz)], 2 alkene methine hydrogen signals [δ 5.19 (1H, brt), 4.96 (1H, brt)], 2 oxygen methine hydrogen signal [δ 6.18 (1H even; D, J=6.1Hz), 5.53 (1H, d, J=6.1Hz)], and 3 groups of methylene hydrogen signals [δ 3.35 (2H, m); 1.97 (2H, m), 1.91 (2H, m)], and 5 groups of methyl hydrogen signals [δ 1.79 (3H, s), 1.48 (3H; S), 1.45 (3H, s), 1.35 (3H, s), 1.30 (3H, s)].
13C-NMR (100MHz, in DMSO-d
6) collection of illustrative plates shows 28 spectral lines altogether, can know in conjunction with DEPT135 and HSQC collection of illustrative plates to comprise 1 carbonyl carbon signal (δ 180.5), 11 sp
2Hydridization quaternary carbon signal (δ 165.3,157.3,155.7,154.1,149.0,135.1,130.6,119.8,105.3,103.1,101.2), wherein 5 is to connect oxygen quaternary carbon, 5 sp
2Hydridization tertiary carbon signal (δ 124.7,123.8,121.0,118.9,107.8); 1 company's oxygen quaternary carbon signal (δ 85.1), 2 company's oxygen tertiary carbon signals (δ 98.1,81.8), (δ 38.9,25.9 for 3 mesomethylene carbon signals; 21.2) 5 methyl carbon signals (δ 25.2,23.1,17.5,17.3,15.8).Comprehensively
1H-NMR,
13C-NMR data, molecular formula and degree of unsaturation can infer that this chemical compound for two benzene pyrrones chemical compounds, contains two hydroxyls in the structure.
1In the H-NMR collection of illustrative plates δ 13.32 (1H, s 1-OH) locate to exist an association phenolic hydroxyl group signal, δ 10.01 (1H, s 7-OH) locate to exist a free phenolic hydroxyl group signal, δ 10.01/C-6 in the HMBC spectrum, C-7, the relevant of C-8 proved that it is connected on the C-7.δ 7.45 (1H, d, J=9.0Hz, H-5), 7.30 (1H, dd, J=9.0,3.0Hz is H-6) with 7.39 (J=3.0Hz H-8) locates three fragrant proton signals and shows that a phenyl ring in the structure has ABX coupling system for 1H, d.δ 7.45/C-7 in the HMBC spectrum, C-8a, C-10a, 7.30/C-8, C-10a, 7.39/C-6, C-7, C-9, C-10a relevant proved that they should belong to and has been H-5, H-6 and H-8.
1H with
13δ in the C-NMR collection of illustrative plates
H(6.18 1H, d, H-4 ')/δ
C(81.8 C-4 '), 5.53 (1H, d, H-5 ')/98.1 (C-5 '), 1.35 (3H, s, H-7 ')/23.1 (C-7 '), 1.30 (3H, s, H-8 ')/17.5 (C-8 '), δ
C85.1 showing, (C-6 ') have one five carbon unit in the structure.Visible following relevant in the HMBC spectrum: H-4 '/C-1, C-2, C-3; H-5 '/C-3, H-7 '/C-5 ', C-6 '; C-8 ' and H-8 '/C-5 ', C-6 ', C-7 '; Deducibility goes out this five carbon unit and is one and is connecting five yuan of peroxide rings of two methyl and be combined in the structure fragment on the dihydrofuran ring that the dihydrofuran ring is connected on the C-2 and C-3 of two benzene pyrrone parent nucleus thus, and two methyl are connected on the C-3 '.
1H with
13δ in the C-NMR collection of illustrative plates
H3.35 (2H, m, H-1 ")/δ
C21.2 (C-1 "), 5.19 (1H, br t, H-2 ")/121.0 (C-2 "), 1.91 (2H, m; H-4 ")/38.9 (C-4 "), 1.97 (2H, m, H-5 ")/25.9 (C-5 "), 4.96 (1H, br t; H-6 ")/123.8 (C-6 "), 1.48 (3H, s, H-8 ")/25.2 (C-8 "), 1.79 (3H, s; H-9 ")/15.8 (C-9 "), 1.45 (3H, s, H-10 ")/17.3 (C-10 "), δ
C135.1 (C-3 "), 130.6 (C-7 ") shows in the structure and to have one 3,7-dimethyl-octa-2,6-dialkylene substituent group.And based on H-1 in the HMBC spectrum " and C-3, it is connected the relevant deduction with C-4a of C-4 on the C-4.Comprehensive HSQC and HMBC collection of illustrative plates belong to the whole carbon signals and the hydrogen signal of this chemical compound.Through the SciFinder network retrieval, do not find relevant report, show that this is new two benzene pyrrones chemical compounds, called after cattle wood ketone A, cracochinchinone A,
1H-NMR with
13The C-NMR data are seen table 3, and its structural formula is following:
Compound C C-6, yellow solid.
366，322，259，243，203。IR (KBr) v
Max3349cm
-1There is hydroxyl to have 1645cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 465 [M+H]
+, ESI-MS (negative) provides m/z 463 [M-H]
-, releasing compound molecular weight is 464.In conjunction with
1H-NMR with
13The C-NMR data confirm that the compound molecule formula is C
28H
32O
6, calculating its degree of unsaturation is 13.With document (Phytochemistry, 2006,67,470-474) report data compare basically identical.So this chemical compound is accredited as passeris montani saturati cage wood ketone B, cochinchinone B.
1H-NMR with
13The C-NMR data are seen table 3, and its structural formula is following:
Table 3.NMR data of CC-5and CC-6 (400MHz for
1H NMR).
aMeasured?in?DMSO-d
6，
bMeasured?in?acetone-d
6.
Compound C C-7; Yellow needle;
372,320,261; 234,203.IR (KBr) v
Max3119cm
-1There is hydroxyl to have 1618cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 397 [M+Na]
+, ESI-MS (negative) provides m/z 395 [M-H]
-, releasing compound molecular weight is 396.In conjunction with
1H-NMR with
13The C-NMR data confirm that the compound molecule formula is C
23H
24O
6, calculating its degree of unsaturation is 12.With document (Bioorganic and Medicinal Chemistry, 2004,12,1947-1953) data of report relatively, basically identical is so this chemical compound is accredited as Lignum Cudraniae tricuspidatae couple benzene pyrrone E, cudratricusxanthone E.
1H-NMR with
13The C-NMR data are seen table 4, and its structural formula is following:
Compound C C-8; Yellow needle, UV λ
nm:383,381; 317; 267,235,202.IR (KBr) v
Max3282cm
-1There is hydroxyl to have 1644cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 403 [M+Na]
+, ESI-MS (negative) provides m/z 379 [M-H]
-, releasing compound molecular weight is 380.In conjunction with
1H-NMR with
13The C-NMR data confirm that the compound molecule formula is C
23H
24O
5, calculating its degree of unsaturation is 12.With document (Chemical and Pharmaceutical Bulletin, 1996,44,232-234) data of report relatively, basically identical, so this chemical compound is accredited as 1,3,7-trihydroxy-2,4-pair of (3-methyl butyl-2-alkene)-two benzene pyrrones.
1H-NMR with
13The C-NMR data are seen table 4, and its structural formula is following:
Table 4.NMR data of CC-7and CC-8 (400MHz for
1H NMR).
aMeasured?in?DMSO-d
6，
bMeasured?in?acetone-d
6.
Compound C C-9; Yellow needle;
363,316,260; 243,204.IR (KBr) v
Max3356cm
-1There is hydroxyl to have 1648cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 433 [M+Na]
+, ESI-MS (negative) provides m/z 409 [M-H]
-, releasing compound molecular weight is 410.In conjunction with
1H-NMR with
13The C-NMR data confirm that the compound molecule formula is C
24H
26O
6, calculating its degree of unsaturation is 12.With document (Natural Products Research, 2006,20,1332-1337) data of report relatively, basically identical is so this chemical compound is accredited as Indonesia Resina garciniae ketone B, dulcisxanthone B.
1H-NMR with
13The C-NMR data are seen table 5, and its structural formula is following:
Compound C C-10, yellow prismatic crystal,
314,258,243,204; IR (KBr) v
Max3402cm
-1There is hydroxyl to have 1600cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 447 [M+Na]
+, ESI-MS (negative) provides m/z 423 [M-H]
-, releasing compound molecular weight is 424.In conjunction with
1H-NMR with
13The C-NMR data confirm that the compound molecule formula is C
25H
28O
6, calculating its degree of unsaturation is 12.With document (Australian Journal of Chemistry, 1970,23,2539-2543) data of report relatively, basically identical, so this chemical compound is accredited as β-mangostin, β-mangostin,
1H-NMR with
13The C-NMR data are seen table 5, and its structural formula is following:
Table 5.NMR data of CC-9and CC-10 (400MHz for
1H NMR, in acetone-d
6).
Compound C C-11 yellow solid,
(c 0.43acetone).IR (KBr) v
Max3449cm
-1There is hydroxyl to have 1643cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 463 [M+Na]
+, ESI-MS (negative) provides m/z 439 [M-H]
-, releasing compound molecular weight is 440.In conjunction with
1H-NMR with
13The C-NMR data confirm that the compound molecule formula is C
25H
28O
7, calculating its degree of unsaturation is 12.With document (Phytochemistry, 2002,60; 541-548) data of report compare, and basically identical is so this chemical compound is accredited as 1; 6-dihydroxy-2-(2-hydroxy-3-methyl butyl-3-alkene)-3,7-dimethoxy-8-(3-methyl butyl-2-alkene)-two benzene pyrrones.
1H-NMR with
13The C-NMR data are seen table 6, and its structural formula is following:
Table 6.NMR data of CC-11 (400MHz for
1H NMR, in DMSO-d
6).
Embodiment 2: the two benzene pyrrones chemical compounds of extraction separation from red bud wood
Get the dry stem 5.0kg of red bud wood (Cratoxylum formosum subsp.pruniflorum); After the coarse crushing, with 8 times of amount 60% (V/V) alcohol-water reflux, extract, twice, each two hours; Merge extractive liquid, obtains the total extractum (675.0g) of red bud wood behind the concentrating under reduced pressure.Get the total extractum (600g) of red bud wood and be dissolved in the suitable quantity of water, filter, get filtrating through the open column chromatography of macroporous resin HP-20, alcohol-water gradient elution.Reclaim under reduced pressure respectively, water elution part (157.3g), 40% (v/v) alcohol-water eluting part (257.0g), and 90% (v/v) alcohol-water eluting part, this part be the total two benzene pyrrone positions of red bud wood (CF, 157.0g).Get 90% (v/v) alcohol-water eluting portion C F (117.0g), adopt the open column chromatography of silica gel, cyclohexane extraction-ethyl acetate gradient elution obtains 8 fractions.Fraction Fr.4 (cyclohexane extraction-ethyl acetate v/v, 9: 1 eluting parts, 4.0g); Through Sephadex LH-20 column chromatography, behind chloroform-methanol (4: the 1) eluting, again through the open column chromatography of silica gel; Cyclohexane extraction-acetone (8: 2) eluting obtains 7 sub-fractions (Fr.4-1～Fr.4-7).Sub-fraction Fr.4-7 is through Sephadex LH-20 column chromatography, and cyclohexane extraction-dichloromethane (1: 1) eluting reaches the open column chromatography of silica gel, and the chloroform-methanol eluting obtains Compound C F-8 (12.6mg), CF-9 (11.6mg), CF-10 (22.5mg) and CF-4 (11.7mg).(13.0g) through the open column chromatography of silica gel, cyclohexane extraction-ethyl acetate gradient elution obtains 8 sub-fractions (Fr.5-1～Fr.5-8) to fraction Fr.5 for cyclohexane extraction-ethyl acetate v/v, 9: 1 eluting parts.Sub-fraction Fr.5-6 (95: 5 eluting parts) separates out crystallization in chloroform-methanol (4: 1), filter to obtain Compound C F-6 (42.5mg).(8.0g), through the open column chromatography of silica gel, cyclohexane extraction-ethyl acetate gradient elution obtains 8 sub-fractions (Fr.6-1～Fr.6-8) to fraction Fr.6 for cyclohexane extraction-ethyl acetate v/v, 8: 2 eluting parts.Sub-fraction Fr.6-2 (9: 1 eluting parts) recrystallization in chloroform-methanol (4: 1) solution obtains Compound C F-11 (30.5mg).Sub-fraction Fr.6-3 (9: 1 eluting parts) is through Sephadex LH-20 column chromatography, and cyclohexane extraction-dichloromethane (1: 1) eluting obtains Compound C F-1 (180.0mg) and CF-12 (16.5mg).Sub-fraction Fr.6-6 (8: 2 eluting parts) is through Sephadex LH-20 column chromatography, and chloroform-methanol (3: 2) eluting reaches the open column chromatography of silica gel, and chloroform-methanol (100: 0) eluting obtains Compound C F-7 (20.0mg) and CF-3 (25.5mg).Sub-fraction Fr.6-8 (eluent ethyl acetate part) is through Sephadex LH-20 column chromatography, and chloroform-methanol (3: 2) eluting obtains Compound C F-5 (14.7mg) and CF-2 (9.3mg).
Through physicochemical constant and modern Wave Spectrum means (MS, NMR), in conjunction with the document related data, identified their structure, as follows.
Annotate: have
*The person is a noval chemical compound.
Compound C F-1, yellow powder, the ferric chloride colour developing is positive, and prompting has phenolic hydroxyl group to exist.UV (MeOH) λ
Max(log ε) 206 (4.73), 235 (4.57), 263 (4.59), 321 (4.34), 374 (4.15) nm; IR (KBr) v
Max3349 (OH), 2914,1618 (C=O), 1481,1292,808cm
-1, HR-ESI-MS provides m/z 427.1748 [M-H]
-(calcd for C
24H
27O
7, 427.1762), the prompting molecular weight is 428, infers molecular formula C
24H
28O
7, calculating degree of unsaturation is 11.
1H-NMR (400MHz, in acetone-d
6) in the collection of illustrative plates, δ
H13.75 (1H, s 1-OH) prompt for the hydroxyl hydrogen signal of hydrogen bond association, δ
H6.80 (H-5), 6.46 (1H, s H-4) are two fragrant hydrogen signals, δ for 1H, s
H3.96 (3H, s, 3-OCH
3) be one group of methoxyl group hydrogen signal, one group of hydrogen signal δ
H(3.31 2H, d, J=7.2Hz, H-1 '), 5.22 (1H, t.J=7.2Hz H-2 '), 1.64 (3H, s, H-4 '), 1.78 (3H, s, H-5 ') prompt for one group of isopentene group substituent group.Another group hydrogen signal δ
H3.48 (2H, t, J=7.2Hz, H-1 "), 1.88 (2H, t, J=7.2Hz, H-2 "), 1.30 (6H, s, H-4 ", H-5 ") prompts for a 3-hydroxy-3-methyl-butyl substituent group.
13C-NMR (100MHz, in acetone-d
6) show 23 spectral lines altogether in the collection of illustrative plates, wherein can know to be the overlapping of two carbon signals from height for one, can know in conjunction with DEPT135, comprise 1 carbonyl carbon signal (δ
C183.1), 11 sp
2Hydridization quaternary carbon signal (δ
C164.4,160.5,156.2,154.0,153.4,141.4,131.4,131.1,112.0,111.5,104.3), 3 sp
2Hydridization tertiary carbon signal (δ
C123.4,101.1,89.7), 1 oxygen quaternary carbon signal (δ of company
C71.2), 3 mesomethylene carbon signal (δ
C44.1,22.5,21.9) and 4 methyl carbon signal (δ
C29.6 * 2,25.8,17.8), 1 methoxyl group signal (δ
C56.4).
Comprehensive above UV, IR,
1H-NMR,
13C-NMR data, molecular formula and degree of unsaturation infer that this chemical compound is two benzene pyrrones chemical compounds.Contain 3 hydroxyl substituents and two C-5 unit substituent groups in the structure, and a methoxyl group substituent group.
In the HMBC collection of illustrative plates, association hydroxyl hydrogen signal δ
H13.75 (1-OH) with carbon signal δ
C160.5 (C-1), 111.5 (C-2), 104.3 (C-9a) are relevant, and the methylene hydrogen signal δ of isopentene group
H(3.31 H-1 ') and carbon signal C-1, C-2,164.4 (C-3) are relevant, confirm that this isopentene group is connected the C-2 position.Methoxyl group hydrogen signal δ
H3.96 (3-OCH
3) relevant with C-3, confirm that this methoxyl group is connected the C-3 position.Fragrance hydrogen signal δ
H6.46 (H-4) and C-3, C-2, C-9a, 156.2 (C-4a) are relevant, confirm that it is connected the C-4 position.Six remaining aromatic carbon signal (δ
C154.0,153.4,141.4,131.1,112.0,101.1) and be the carbon signal on another phenyl ring.Methylene hydrogen signal δ
H3.48 (H-1 "), 1.88 (H-2 ") and carbon signal δ
C131.1 (C-8) relevant, fragrant hydrogen signal δ
H6.80 (H-5) with carbon signal δ
C154.0 (C-10a), 153.4 (C-6), 141.4 (C-7), 112.0 (C-8a) confirm and should be positioned at carbon signal δ by fragrance hydrogen H-5
C131.1 the chemical displacement value of H-5 is considered in para-position (C-8), confirms that it is connected the C-5 position.So this chemical compound is accredited as 1,6,7-trihydroxy-2-(3-methyl butyl-2-alkene)-3-methoxyl group-8-(3-hydroxyl-3-methoxyl group butyl)-two benzene pyrrones through the SciFinder network retrieval, does not find relevant report, shows that this is a noval chemical compound.
1H-NMR with
13The C-NMR data are seen table 7.Its structural formula is following:
Compound C F-2, yellow powder, the ferric chloride colour developing is positive, and prompting has phenolic hydroxyl group to exist.UV (MeOH) λ
Max(log ε) 206 (4.73), 235 (4.57), 263 (4.59), 321 (4.34), 374 (4.15) nm; IR (KBr) v
Max3349 (OH), 2914,1618 (C=O), 1481,1292,808cm
-1, HR-ESI-MS provides m/z 463.2132 [M-H]
-(calcd forC
28H
31O
6, 463.2126), the prompting molecular weight is 464, infers molecular formula C
28H
32O
6, calculating degree of unsaturation is 13.
1H-NMR (400MHz, in acetone-d
6) in the collection of illustrative plates, δ
H13.47 (1H, s 1-OH) prompt for the hydroxyl hydrogen signal of hydrogen bond association, δ
H7.56 (H-8), 6.97 (1H, s H-5) are two fragrant hydrogen signals, one group of hydrogen signal δ for 1H, s
H(3.43 2H, d, J=7.0Hz, H-1 '), 5.24 (1H, t, J=7.0Hz, H-2 '), 1.66 (3H, s, H-4 '), 1.79 (3H, s, H-5 ') prompt for one group of isopentene group substituent group.Another group hydrogen signal δ
H3.57 (2H, d, J=7.0Hz, H-1 "), 5.24 (1H, t, J=7.0Hz; H-2 "), 1.99 (2H, m, H-4 "), 2.06 (2H, m, H-5 "); 5.02 (1H, t, J=6.6Hz, H-6 ") 1.52 (3H, s, H-8 "), 1.90 (3H; S, H-9 "), 1.50 (3H, s, H-10 ") prompt for one 3,7-dimethyl-octa-2,6-dialkylene substituent group.
13C-NMR (100MHz, in acetone-d
6) show 27 spectral lines altogether in the collection of illustrative plates, wherein can know to be the overlapping of two carbon signals from height for one, can know in conjunction with DEPT135, comprise 1 carbonyl carbon signal (δ
C180.8), 13 sp
2Hydridization quaternary carbon signal (δ
C160.2,158.8,154.0,153.9,152.6,143.8,135.9,132.3,131.6,113.7,110.5,106.5,103.3), 5 sp
2Hydridization tertiary carbon signal (δ
C124.9,123.2 * 2,109.2,103.4), 4 mesomethylene carbon signal (δ
C40.3,27.2,22.4,22.1), 5 methyl carbon signal (δ
C25.8,25.7,17.9,17.6,16.4), comprehensive above UV, IR,
1H-NMR,
13C-NMR data, molecular formula and degree of unsaturation infer that this chemical compound is two benzene pyrrones chemical compounds.Contain 4 hydroxyl substituents in the structure, a C-5 unit substituent group, and a C-10 unit substituent group.
In the HMBC collection of illustrative plates, association hydroxyl hydrogen signal δ
H13.47 (1-OH) with carbon signal δ
C158.5 (C-1), 110.5 (C-2), 103.3 (C-9a) are relevant, and the methylene hydrogen signal δ of isopentene group
H(3.43 H-1 ') and carbon signal C-1, C-2,160.2 (C-3) are relevant, confirm that this isopentene group is connected the C-2 position.Methylene hydrogen signal δ
H3.57 (106.5 (C-4) are relevant for H-1 ") and carbon signal C-3,154.0 (C-4a), confirm this 3,7-dimethyl-octa-2, the 6-dialkylene is connected the C-4 position.Fragrance hydrogen signal δ
H7.56 (H-8) with 6.97 (H-5) all with carbonyl carbon signal δ
C180.8 (C-9) relevant, confirm that they are connected C-8 or C-5 position.Consider their chemical displacement value, confirm that the proton of its low place is connected the C-8 position.So this chemical compound is accredited as 1,3,6,7-tetrahydroxy-2-(3-methyl butyl-2-alkene)-4-(3,7-dimethyl octyl group-2,6-diene)-two benzene pyrrones through the SciFinder network retrieval, does not find relevant report, shows that this is a noval chemical compound.
1H-NMR with
13The C-NMR data are seen table 7.Its structural formula is following:
Table 7.NMR Data of CF-1 and CF-2 (400MHz for
1H NMR, in acetone-d
6)
aSignals?may?be?interchangeable?in?each?column.
Compound C F-3, pale brown toner end, the ferric chloride colour developing is positive, and prompting has the existence of phenolic hydroxyl group.ESI-MS (negative) provides m/z 327 [M-H]
-, 655 [2M-H]
-, the prompting molecular weight is 328.
1H-NMR composes (400MHz, in acetone-d
6) in, 13.43 (1H, s, 1-OH) associating phenolic hydroxyl group hydrogen signal of prompting, the fragrant hydrogen signal 7.60 (1H of one group of mutual coupling; D, J=8.7, H-8), 6.99 (1H; D, J=8.7, H-7) prompting is one 1,2; 3, the existence of 4-four substituted benzene rings, fragrant hydrogen signal 6.30 (1H, s) existence of one five substituted benzene ring of prompting.One group of hydrogen signal 6.59 (1H, dd, J=17.5,10.6Hz, H-2 '), 5.10 (1H, br d, J=17.5Hz, H-3 '), 4.94 (1H, br d, J=10.6Hz, H-3 '), 1.75 (6H, s, H-4 ', 5 ') prompting 2-(2-methyl fourth-3-alkene) existence.With document (Chemical andPharmacetical Bulletin, 1997,45 (10), 1615-1619) in the two benzene pyrrone A data basically identicals of different Lignum Cudraniae tricuspidatae of report, be different Lignum Cudraniae tricuspidatae couple benzene pyrrone A so identify this chemical compound, isocudraxanthone A.
1The H-NMR data are seen table 8, and its structural formula is following:
Compound C F-4, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 341 [M-H]
-, the prompting molecular weight is 342.In conjunction with
1H-NMR with
13The C-NMR data infer that its molecular formula is C
19H
18O
6, calculating degree of unsaturation is 11.With document (Phytochemistry, 1972,11 (6), the data in 2089-2092.) relatively, basically identical is different three-bristle cudrania 1,5 so identify this chemical compound, 6-trihydroxy-3-methoxyl group-4-(2-methyl butyl-3-alkene-2-yl)-two benzene pyrrones.
1H-NMR with
13The C-NMR data are seen table 8.Its structural formula is following:
Table 8.NMR Data of CF-3and CF-4 (400MHz for
1H NMR)
a：Measured?in?Acetone-d
6，
b：Measured?in?CDCl
3+CD
3OD
Compound C F-5, pale yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 341 [M-H]
-, ESI-MS (positve) provides m/z 343 [M+H]
+, the prompting molecular weight is 342.In conjunction with
1H-NMR with
13The C-NMR data infer that its molecular formula is C
19H
18O
6, calculating degree of unsaturation is 11.With document (Phytochemistry, 1996,43 (2), the data in 513-520) relatively, basically identical is 1 so identify this chemical compound, 6-dihydroxy-5-methoxyl group-4 ', 5 '-dihydro-4 ', 4 ', 5 '-the trimethyl furan [2 ', 3 ': 3,4]-two benzene pyrrones.
1H-NMR with
13The C-NMR data are seen table 9.Its structural formula is following:
Compound C F-6, pale brown toner end, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 311 [M-H]
-, 623 [2M-H]
-, the prompting molecular weight is 312.In conjunction with
1H-NMR with
13The C-NMR data infer that its molecular formula is C
18H
16O
5, calculating degree of unsaturation is 11.With document (Phytochemistry, 1993,33 (3), the data in 727-728) relatively, basically identical is 1,3 so identify this chemical compound, 7-trihydroxy-2-(3-methyl butyl-2-alkene)-two benzene pyrrones.
1H-NMR with
13The C-NMR data are seen table 9.Its structural formula is following:
Table 9.NMR Data of CF-5and CF-6 (400MHz for
1H NMR, in acetone-d
6)
Compound C F-7, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 393 [M-H]
-, 787 [2M-H]
-, ESI-MS (positive) provides m/z 417 [M+Na]
+, 811 [M+Na]
+, the prompting molecular weight is 394.In conjunction with
1H-NMR with
13The C-NMR data infer that its molecular formula is C
23H
22O
6, calculating degree of unsaturation is 13.With document (Phytochemistry, 1986,25 (5), the data in 1217-1219) relatively, basically identical is couple benzene pyrrone V so identify this chemical compound
1, xanthone V
1 1H-NMR with
13The C-NMR data are seen table 10.Its structural formula is following:
Table 10.NMR data of CF-7 (400MHz for 1H NMR, in acetone-d
6).
Compound C F-8, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 257 [M-H]
-, the prompting molecular weight is 258.In conjunction with
1H-NMR with
13The C-NMR data infer that its molecular formula is C
14H
10O
5, calculating degree of unsaturation is 10.With document (Phytochemistry, 1998,49 (7), the data in 2159-2162) relatively, basically identical is 1 so identify this chemical compound, 7-dihydroxy-8-methoxyl group-two benzene pyrrones.
1H-NMR with
13The C-NMR data are seen table 11.Its structural formula is following:
Compound C F-9, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 227 [M-H]
-, 455 [2M-H]
-, the prompting molecular weight is 228.In conjunction with
1H-NMR with
13The C-NMR data infer that its molecular formula is C
13H
8O
4, calculating degree of unsaturation is 10.With document (Journal of ChemicalCrystallography, 2005,35 (1), the data in 23-25) relatively, basically identical is 1 so identify this chemical compound, 7-dihydroxy-two benzene pyrrones.
1H-NMR with
13The C-NMR data are seen table 11.Its structural formula is following:
Table 11.NMR Data of CF-8and CF-9 (400MHz for
1H NMR)
a：Measured?in?CDCl
3，
b：Measured?in?CDCl
3+CD
3OD
Compound C F-10, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 273 [M-H]
-, the prompting molecular weight is 274.In conjunction with
1H-NMR with
13The C-NMR data infer that its molecular formula is C
14H
10O
6, calculating degree of unsaturation is 10.With document (Phytochemistry, 1996,42 (4), the data in 1195-1198) relatively, basically identical is 1,4 so identify this chemical compound, 7-trihydroxy-8-methoxyl group-two benzene pyrrones.
1H-NMR with
13The C-NMR data are seen table 12.Its structural formula is following:
Compound C F-11, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 258 [M-H]
-, 515 [2M-H]
-, the prompting molecular weight is 258.In conjunction with
1H-NMR with
13The C-NMR data infer that its molecular formula is C
14H
10O
5, calculating degree of unsaturation is 10.With document (Phytochemistry, 1998,49 (7), the data in 2159-2162) relatively, basically identical is 1 so identify this chemical compound, 7-dihydroxy-4-methoxyl group-two benzene pyrrones.
1H-NMR with
13The C-NMR data are seen table 12.Its structural formula is following:
Table 12.NMR Data of CF-10and CF-11 (400MHz for
1H NMR, in acetone-d
6)
Compound C F-12, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 273 [M-H]
-, the prompting molecular weight is 274.In conjunction with
1H-NMR with
13The C-NMR data infer that its molecular formula is C
14H
10O
6, calculating degree of unsaturation is 10.With document (Journal of Pharmaceutical andBiomedical Analysis, 2007,45 (7), the data in 793-798) relatively, basically identical is 1,3 so identify this chemical compound, 6-dihydroxy-7-methoxyl group-two benzene pyrrones.
1H-NMR with
13The C-NMR data are seen table 13.Its structural formula is following:
Table 13.NMR Data of CF-12 (400MHz for
1H NMR, in DMSO-d
6)
Embodiment 3: each chemical compound is to the influence of retinol receptor RXR alpha transcriptional mobilizing function experiment
With African green monkey kidney cell CV-1 with 1.8 * 10
4/ hole is inoculated in 96 well culture plates, cultivates 24 hours for 37 ℃; The cell of 80-90% degree of converging is changed liquid, and in cell, transfection was changed liquid after 6 hours with liposome transfection purpose plasmid, continued 37 ℃ and cultivated 18 hours; Dosing in 24 hours behind the cell transfecting, medicine and positive control drug 9-are made into the 10mg/ml storage liquid with DMSO along tretinoin, face the culture fluid that contains 10% (V/V) FBS (hyclone) with preceding usefulness and are diluted to required concentration; Behind the medicine continuous action 24 hours; Collecting cell carries out β-Gal enzyme detection and reporter gene CAT enzyme respectively and detects; β-Gal enzyme testing result is proofreaied and correct the result that the CAT enzyme detects, and calculates relative CAT enzymatic activity.Its result is shown in Fig. 1-4.It is thus clear that separate the transcription activating function of the inhibition retinol receptor RXR α that the two benzene pyrrones chemical compounds obtain can be in various degree, can intervene physiology, pathological processes such as the various kinds of cell propagation regulated and control by retinol receptor RXR α, differentiation, apoptosis.Further research shows, Compound C C-1, and CC-2, CC-6, CF-5 presents dose dependent (Fig. 5-7) to the Transcription of retinol receptor RXR α.
Embodiment 4: the two benzene pyrrones chemical compounds of the present invention are to the lethal effect of tumor cell
We adopt the inhibitory action of mtt assay test compounds to tumor cell.Select degrees of fusion 80%, the cell of logarithmic (log) phase growth is used trypsinization, shifts, and is centrifugal, removes supernatant, with the DMEM culture fluid suspendible that contains 10%FBS (the calf fetal blood of deactivation is clear) of new preparation.Various cells are with 1.0 * 10
4/ hole is inoculated in 96 well culture plates and adds successively simultaneously all that 5 differences are dilution waits to sieve the sample medicinal liquid, and each dilution factor repeats 3 holes, simultaneously parallel solvent control of doing same concentrations; And the negative control of not dosing, cultivated 72 hours MTT dyeing for 37 ℃; OD is measured in the DMSO decolouring
570, calculate inhibition rate of tumor growth IR (%)=(blank OD meansigma methods-administration group OD meansigma methods)/blank OD meansigma methods * 100.Experimental result is referring to table 14.The result shows, the cattle wood among embodiment 1 and the embodiment 2 and the total two benzene pyrrone positions of red bud wood and 12 pairs of benzene pyrrones chemical compounds are to 4 kinds of tumor cells of human body: breast cancer cell MCF-7; Non-small lung cancers cell H-460; Prostate gland cancer cell LNCaP; The propagation of cervical cancer cell Hela has inhibitory action in various degree.
Table 14: the external tumor experimental data that presses down of two benzene pyrrones chemical compounds
Embodiment 5: the preparation of the total two benzene pyrrone positions of cattle wood granule
Get the total two benzene pyrrone position 5g of embodiment 1 gained cattle wood and mix, add water and process soft material, cross 12 mesh sieves and carry out pelletize, obtain granule after the drying with starch 25g.In this granule, contain total two benzene pyrrone position 50mg among every 300mg.
Embodiment 6: the preparation of cattle wood and the total two benzene pyrrone position mixing tablets of red bud wood
Get wooden total two each 5g of benzene pyrrone position of total two benzene pyrrone positions of embodiment 1 gained cattle wood and the red bud of embodiment 2 gained and mix with sodium carboxymethyl cellulose 46g and Pulvis Talci 4g, mixture breaks into diameter 6mm with single punch tablet machine, the sheet of weight 300mg.Every contains total two benzene pyrrone position 50mg in this tablet.
Embodiment 7:1,6-dihydroxy-5-methoxyl group-4 ', 4 '-dimethyl-4,5-dihydropyran-6 '-ketone-[2 ', 3 ': 3,4]-preparation of two benzene pyrrones (CC-2) tablet
Embodiment 8:1,6, the preparation of 7-trihydroxy-2-(3-methyl butyl-2-alkene)-3-methoxyl group-8-(3-hydroxyl-3-methoxyl group butyl)-two benzene pyrrones (CF-1) capsule
Embodiment 9:1,3,7-trihydroxy-2-(3-methyl butyl-2-alkene)-4-(7-methoxyl group-3; 7-dimethyl octyl group-2, the 5-diene)-two benzene pyrrones (CC-3) and 1,3; 6; The preparation of 7-tetrahydroxy-2-(3-methyl butyl-2-alkene)-4-(3,7-dimethyl octyl group-2,6-diene)-two benzene pyrrones (CF-2) epoxy glue wafer
Each capsule contains two benzene pyrrones chemical compound 20mg.
Embodiment 10: embodiment 6,8 and 9 sample are to the tumor growth inhibitory action of transplanted tumor in nude mice
(1) inoculation:
Adopt subcutaneous vaccination that human lung adenocarcinoma cell A549 is inoculated in the nude mice (4～6 ages in week, the scale of construction 18～22g, male and female half and half) of BALB/c-nu/nu strain, every nude inoculation tumor cell quantity is (1-5) * 10
6
(2) divide into groups:
Be divided into treatment group 61 (embodiment 6 low dose group), treatment group 62 (embodiment 6 high dose group), treatment group 81 (embodiment 8 low dose group), treatment group 82 (embodiment 8 high dose group), treatment group 91 (embodiment 9 low dose group), treatment group 92 (embodiment 9 high dose group), positive controls (cyclophosphamide 30mg/kg) and negative control group (give isopyknic normal saline) with the nude mice random packet next day behind the tumor inoculation.
(3) administration time, dosage and route of administration:
The volume of treating nude mice oxter tumor piece grows to 150～200mm
3The time begin administration, low dose group is 50mg/kg, high dose group is 150mg/kg; Administering mode is a gastric infusion.
(4) evaluation criterion
Behind the nude mice successive administration 15 days, put to death next day, the allocation tumor tissue is weighed, and calculates tumour inhibiting rate according to formula:
Tumour inhibiting rate (%)=(blank control group tumor weight-administration group tumor is heavy)/blank control group tumor heavy * 100
Therapeutic evaluation standard: tumour inhibiting rate %＞40% and be effective through statistical procedures P＜0.05.
Experimental result shows: the high and low dose group does not all have nude mice death, and the nude mice weight increase is normal; Compare with the normal saline matched group, high-dose therapy group tumor is heavy obviously to be alleviated, and the tumour inhibiting rate of treatment group is respectively 22.7%, 43.5%, 17.6%, 42.3%, 29.4%, 46.7%.(seeing table 15).
Table 15 is respectively organized the average weight and the tumour inhibiting rate of transplanted tumor
**：P＜0.05
The foregoing description is a preferred implementation of the present invention; But embodiment of the present invention is not restricted to the described embodiments; Other any do not deviate from change, the modification done under spirit of the present invention and the principle, substitutes, combination, simplify; All should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (6)
1. compositions, it is characterized in that: said composition is made up of following pair of benzene pyrrones chemical compound: 1,5-dihydroxy-4 ', 4 '-dimethyl-6 '-hydroxyl-4 ', 5 '-dihydropyran [2 '; 3 ': 3,4]-two benzene pyrrones, 1,6-dihydroxy-5-methoxyl group-4 ', 4 '-dimethyl-4; 5-dihydropyran-6 '-ketone-[2 ', 3 ': 3,4]-two benzene pyrrones, 1,3; 7-trihydroxy-2-(3-methyl butyl-2-alkene)-4-(7-methoxyl group-3,7-dimethyl octyl group-2,5-diene)-two benzene pyrrones, 1,7-dihydroxy-4-(3; 7-dimethyl octyl group-2, the 6-diene)-5 '-(1-hydroxyl-1-Methylethyl)-4 ', 5 '-dihydrofuran [2 ', 3 ': 3; 2]-and two benzene pyrrones, cattle wood ketone A, 1,6,7-trihydroxy-2-(3-methyl butyl-2-alkene)-3-methoxyl group-8-(3-hydroxyl-3-methoxyl group butyl)-two benzene pyrrones and 1,3; 6, more than one in 7-tetrahydroxy-2-(3-methyl butyl-2-alkene)-4-(3,7-dimethyl octyl group-2,6-diene)-two benzene pyrrones; The structural formula of said cattle wood ketone A is shown below:
2. compositions according to claim 1; It is characterized in that: the method for preparing of said pair of benzene pyrrones chemical compound is by following operating procedure: the dry stem of Guttiferae cattle fogfruit cattle wood or red bud wood is ground into coarse powder; Immerse to extract in the solvent cold extraction or heating and refluxing extraction in extracting solvent; Filter or the centrifugal insoluble matter of removing, again gained is extracted solution and carry out concentrating under reduced pressure, separate obtaining two benzene pyrrones chemical compounds.
3. compositions according to claim 2 is characterized in that: said extraction solvent is that volume fraction is 60% ethanol; Said method for distilling is a reflux, extract,, and said extraction time is 6 hours; Said separation is to adopt chromatography method and/or extraction to separate.
4. the application of compositions according to claim 1 in preparation rxr receptor transcription inhibitor.
5. a compositions as claimed in claim 1 is applied to prepare food or the pharmaceuticals that prevent or treat cancer as the rxr receptor transcription inhibitor.
6. application according to claim 5 is characterized in that: said rxr receptor transcription inhibitor and pharmaceutically acceptable carrier are mixed and made into powder, tablet, capsule, pill, suppository, enteric agents, injection, syrup, Emulsion, suspensoid, tincture, unguentum or spray.
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