CN101602754B - Flavanone derivatives, preparation method and use thereof - Google Patents

Flavanone derivatives, preparation method and use thereof Download PDF

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CN101602754B
CN101602754B CN2009100749512A CN200910074951A CN101602754B CN 101602754 B CN101602754 B CN 101602754B CN 2009100749512 A CN2009100749512 A CN 2009100749512A CN 200910074951 A CN200910074951 A CN 200910074951A CN 101602754 B CN101602754 B CN 101602754B
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flavanone
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dihydroxyl
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CN101602754A (en
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李青山
石磊
韩玲革
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Abstract

The invention relates to polyphenol substances, a synthesis method and use thereof, in particular to flavanone derivatives, a preparation method and use thereof, which solves the problem that the prior natural flavanone compounds are difficult to extract, not easy to obtain and incapable of extensive use. The compounds have a structure (as above), wherein R1, R2 and R3 are selected from hydrogen,1 to 8 carbonic alkyl groups, halogen, nitro group, 1 to 8 carbonic alkoxy or amino groups respectively; R4 and R5 can be selected from 1 to 8 carbonic alkyl groups, 1 to 8 alkoxy or alkenyl groups respectively; and the compounds are obtained through the reaction of compound 6-hydroxy-2,4-hydroxy acetophenone substances and aromatic aldehydes or heterocyclic aldehyde substances in polyalcohol solvent by taking high-boiling-point acid as a catalyst, and can be applied to the preparation of medicaments for resisting tumors and cardiovascular and cerebrovascular diseases. The flavanone derivatives have the activity of resisting tumors and inhibiting the cardiovascular and cerebrovascular diseases, thereby opening up a new way for preparing the medicaments and bringing new breakthroughs for the medicament field. Moreover, the synthesis method has the advantages of mild conditions and easy operation.

Description

A kind of flavanone derivatives
Technical field
The present invention relates to polyphenols and preparation method and use thereof, be specially a kind of flavanone derivatives.
Background technology
Flavanone kind composition is one type of polyphenols that extensively distributes at nature.Flavanone kind composition has wide biological activity and pharmacologically active.Big quantity research shows, flavanone kind composition has the radical of removing, anti-oxidant, mutation, antitumor, antibiotic, antiviral and regulate immunity, treatment of vascular sclerosis, function such as hypoglycemic, and it is active to also have part to be proved to be anti HIV-1 virus.Yet flavanone kind composition is one type low-molecular-weightly is distributed widely in botanic natural plant composition, is the metabolite of plant polyphenol kind, is considered to one type of micro-flavonoid, because it is relatively limited in distributed in nature.Therefore naturally occurring flavanone kind composition is difficult to extract, and is difficult to obtain, and can't be used widely.So people through big quantity research, take artificial synthesis to obtain various flavanone kind compositions usually, but up to the present, do not appear in the newspapers for 5,7 dihydroxyl-6,8 alkyl or the substituted flavanone kind composition of alkylene and compound method thereof.For the active rule of the flavanone of inquiring into this type of brand new, and, need more structural and active bonded instance in order to find the active chemicals that better has the flavanone skeleton.
Summary of the invention
The problem that the present invention is difficult to extract in order to solve existing natural flavanone kind composition, is difficult to obtain, can't widespread use provides a kind of flavanone derivatives.
The present invention adopts following technical scheme to realize: a kind of flavanone derivatives, and structure is following:
Figure G2009100749512D00021
Wherein: R 1, R 2, R 3Can be identical or different, be selected from alkyl, halogen, the nitro of hydrogen, a 1-8 carbon, the alkoxyl group or the amino of a 1-8 carbon respectively, R 1, R 2And/or R 3Can replace or unsubstituted fused ring compound with forming with phenyl ring is thick; R 4, R 5Can be identical or different, be selected from the alkyl of 1-8 carbon, the alkoxyl group or the alkylene of a 1-8 carbon respectively, the hydroxyl hydrogen on a ring can be the metal alkali (such as sodium salt, magnesium salts ion etc.) of hyoscine, and the b ring can be heterogeneous ring compound; In the said structure 2; 3 steric configuration is respectively R configuration or S configuration; Perhaps in the said structure 2; 3 steric configuration is R configuration and S configuration simultaneously, and the implication of these words is that institute of the present invention synthetic compound can be single R configuration or the optically active compound of S configuration behind method purifying such as column chromatography, recrystallization, also can be not purified and comprises the mixture of the steric isomer of R configuration and S configuration when having same two dimensional structure.
Prepare the method for described flavanone derivatives, synthetic route is following:
Figure G2009100749512D00022
R wherein 1, R 2, R 3, R 4, R 5Definition such as claim 1
The concrete steps of said synthesis route are: with compound 6-hydroxyl-2,4 hydroxy acetophenone class material is starting raw material, in polyol solvent; With high boiling point acid as catalyzer; Obtain corresponding flavanone derivatives with aromatic aldehyde or heterocycle aldehydes substance reaction, above-mentioned temperature of reaction is 50-200 ℃, and the reaction times is 1-15 hour; The mol ratio of compound 6-hydroxyl-2,4 hydroxy acetophenone class material, aromatic aldehyde or heterocycle aldehyde material and catalyzer is 1: 1.0～5.0: 1.0～5.0.Said polyol solvent can be methyl alcohol, ethanol and terepthaloyl moietie, and glycol ether, glycerine etc., said catalyzer can be boric acid, Hydrocerol A, tartrate etc.
Flavanone derivatives according to scheme preparation according to the invention has anti-tumor activity and suppresses the cardiovascular and cerebrovascular diseases activity, so institute of the present invention synthetic flavanone derivatives can be applied to prepare in the medicine of antitumor and cardiovascular and cerebrovascular diseases.When compound of the present invention or their mixture are used to prepare antitumor drug and cardiovascular and cerebrovascular diseases medicament; Can process injection, tablet, capsule, suppository, film, pill according to the ordinary method of field of medicaments; Drug form such as externally-applied liniment, ointment, this is that those of ordinary skill in the art knows.
The present invention utilize aforesaid method synthetic part preferred compound have:
Compound 1-a:6 ' hydroxyl-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-b:4 ' chloro-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-c:6 ' chloro-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-d:4 ' nitro-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-e:6 ' nitro-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-f:4 ' hydroxyl 6 ' methoxyl group-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-g:4 ' methoxyl group-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-h:6 ' methoxyl group-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-i:4 ', 6 ' dimethoxy-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-j:4 ', 6 ' dihydroxyl-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-k:4 ', 5 ' dimethoxy-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-l:4 ', 5 ' dihydroxyl-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-m:4 ', 6 ' two chloro-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-n:2-(furans-2-yl)-5,7-dihydroxyl-6,8-methyl-chromanone
Compound 1-o:4 ' hydroxyl-5,7 dihydroxyl-6,8-dimethoxy flavanone;
Amino-5,7 dihydroxyl-6 of compound 1-p:4 ', 8-dimethyl-flavanone;
Compound 1-q:4 ' methyl-5,7 dihydroxyl-6,8-dimethyl-flavanone;
Compound 1-r:5,7 dihydroxyl-6 methyl-8-allyl group flavanone;
Structural formula is distinguished as follows:
Figure G2009100749512D00041
Figure G2009100749512D00051
Figure G2009100749512D00061
The determination of pharmacological activity of the compound of the present invention's preparation:
Above-mentioned part flavanone kind composition of synthetic and salt thereof are carried out preliminary antitumor activity screening; Measure the anti-tumor activity of this compounds through mtt assay; The result shows that this compounds has certain cytotoxic activity to different tumour cells, points out this compounds to have certain antitumor efficacy; Part of compounds has been carried out the Human umbilical vein endothelial cells proliferation experiment, shown that it has proliferation function preferably, shown that this type of medicine has certain protective role in to blood vessel injury; Part of compounds has been carried out the inhibition activity experiment of serum induction of vascular smooth muscle cell proliferation, shown that it just has very high inhibition active, can effectively prevent and treat atherosclerotic formation.
(1) extracorporeal suppression tumor cell proliferation activity experiment
Adopt mtt assay to carry out experiment in vitro,, get nutrient solution and be made into the individual cells suspension with containing 10% tire calf serum with the HepG-2 liver cancer cell, with every hole 1000-10000 cell inoculation to 96 orifice plates, every pore volume 200ul.Cultivated 3-5 days, and added above-mentioned synthetic compound 1-b, cultivate after 1 day, every hole adds MTT solution 20ul. continued to hatch 4 hours, stop to cultivate, and careful the suction abandoned the culture supernatant liquid hole in, for suspension cell need centrifugal after again suction abandon culture supernatant liquid in the hole.Every hole adds 150ul DMSO, vibrates 10 minutes, and crystallisate is fully melted.Select the 490nm wavelength, on the enzyme linked immunological monitor, measure each hole absorbance value, the record result is an X-coordinate with time, and light absorption value is that ordinate zou is drawn cell growth curve.Experimental result sees the following form 1:
Figure G2009100749512D00071
Table 1-different concns compound 1-b suppresses the influence of HepG-2 hepatoma cell proliferation
Conclusion: compound 1-b has restraining effect to the HepG-2 liver cancer cell when concentration 12.5ug/ml; Inhibiting rate reaches more than 50% when concentration 25ug/ml, explains that flavanone (is example with the compound 1-b) compound of such brand new has certain inhibition tumor cell proliferation activity.
(2) vitro human huve cell proliferation activity experiment
Adopt mtt assay to carry out experiment in vitro,, get nutrient solution and be made into the individual cells suspension with containing 10% tire calf serum with Human umbilical vein endothelial cells, with every hole 1000-10000 cell inoculation to 96 orifice plates, every pore volume 200ul.Cultivated 3-5 days, and added above-mentioned synthetic compound 1-n, cultivate after 1 day, every hole adds MTT solution 20ul. continued to hatch 4 hours, stop to cultivate, and careful the suction abandoned the culture supernatant liquid hole in, for suspension cell need centrifugal after again suction abandon culture supernatant liquid in the hole.Every hole adds 150ul DMSO, vibrates 10 minutes, and crystallisate is fully melted.Select the 490nm wavelength, on the enzyme linked immunological monitor, measure each hole absorbance value, the record result is an X-coordinate with time, and light absorption value is that ordinate zou is drawn cell growth curve.Experimental result sees the following form 2:
Blank Negative control 50ug/ml 25ug/ml 12.5ug/ml 6.25ug/ml
MV 0.2975 0.251 0.3965 0.358375 0.35375 0.346875
The IC value -0.58 -0.428 -0.409 -0.382
The t check P＜0.01 P＜0.01 P＜0.01 P＜0.01
The influence of table 2-different concns compound 1-n Human umbilical vein endothelial cells propagation
Conclusion: compound 1-n has short proliferation function to Human umbilical vein endothelial cells HUVEC when concentration 6.25ug/ml; Inhibiting rate reaches more than 50% when concentration 25ug/ml, explains that flavanone (is example with the compound 1-n) compound of such brand new has certain short proliferation function to Human umbilical vein endothelial cells HUVEC.
(3) the inhibition activity experiment of serum induction of vascular smooth muscle cell proliferation
(vascular smooth muscle cell, VSMC) propagation and phenotypic alternation are atherosclerotic main pathological basis to VSMC.Increasing evidence shows that atherosclerosis is an excessive inflammatory response to blood 00 pipe damage.Behind the blood vessel injury, monocyte, thrombocyte and lymphocyte are attached to vessel wall, discharge a series of cytokines and peptide class growth factor, combine with specific receptors, influence VSMC phenotype and growth signals, have therefore promoted the generation of fiber propagation pathology in late period.VSMC is one of main cellular constituent that constitutes vessel wall, and in the atherosclerotic lesion of blood vessel, outgrowth VSMC is a topmost composition in the atheromatous plaque.Collagen in the extracellular matrix also affects propagation and the differentiation of VSMC except being the important composition composition in the AP, therefore in atherosclerosis formation and development process, also plays an important role.
Experiment material and method: DMEM (Dulbecco ' s Modified Eagle Medium) available from Gibco company; Tetrazolium bromide (MTT), trypsinase are all available from Sigma company; Standard foetal calf serum (FBS) is available from Hyclone company; Microplate optical detecting appearance; Microscope.
FBS induces the foundation and the screening of VSMC cell proliferation model: former be commissioned to train nourish blood the pipe smooth muscle cell use 0.125% trysinization, be inoculated in 96 orifice plates, cultivate 24 hours to subconfluence.Changing serum-free culture 24h into makes cell be tending towards static (G 0Phase), adds compound 1-e and handle after 4 hours, add 10%FBS and cultivated 20 hours.Detect the propagation situation of cell with mtt assay.
Conclusion: compound 1-e can reach 50% to serum induction of vascular smooth muscle cell proliferation inhibiting rate when concentration 3.17ug/ml, explains that flavanone (is example with the compound 1-e) compound of such brand new is active to the good inhibition of having of serum induction of vascular smooth muscle cell proliferation.
Compared with prior art; The present invention is with compound 6-hydroxyl-2; 4 hydroxy acetophenone class materials and aromatic aldehyde or heterocycle aldehydes substance reaction obtain corresponding flavanone derivatives; Show that through above-mentioned pharmacological activity test institute of the present invention synthetic compound has the biological activity of anti-tumor activity and inhibition cardiovascular and cerebrovascular diseases; This compounds has the effect of the tumor cell proliferation of inhibition, also has short Human umbilical vein endothelial cells proliferation function, demonstrates the activity that has the ultra oxyradical of external removing, suppresses the lipoperoxide generation of free yl induction.Above activity shows that this compounds can be expected and is used for preparation prevention or medicine for treating tumor thing or drug combination, can be used for blood vessel injury protection medication and cardiovascular system diseases medication and caused or other physiological changes relevant with oxyradical or the medicine of disease by oxyradical.The present invention has opened up new approach for the preparation said medicine, brings new breakthrough at field of medicaments, and this compound method mild condition, and is easy and simple to handle.
Embodiment
Embodiment 1: compound 1-a: the preparation of (6 ' hydroxyl-5,7 dihydroxyl-6,8-dimethyl-flavanone):
With 200 milligrams of (0.001mol) 6-hydroxyl-2,4 hydroxyl-3,5 dimethyl acetophenones, 125 milligrams of (0.001mol) 2-hydroxy benzaldehydes, 61 milligrams of (0.001mol) boric acid are dissolved in a small amount of terepthaloyl moietie, heat up in 100 ℃ stirring reaction 1 hour; Reactant is used dissolve with ethanol, get 30 milligrams of light green materials through column chromatography, yield 15%, HNMR (500MHz, DMSO), δ 7.02 (2H, d; J=8.4Hz, H-e), 6.75 (1H, d, J=8.5Hz, H-d), 6.65 (1H; D, J=8.5Hz, H-d), 5.58 (1H, dd, J=12.3,2.7Hz; H-c), 3.18 (1H, dd, J=17.0,12.5Hz, H-b 2), 2.86 (1H, dd, J=17.0,3.0Hz, H-b 1), 1.97 (6H, d, J=4.5Hz, H-a) ESI-MS (m/z): [M-1] -=299.
Embodiment 2: compound 1-b: the preparation of (4 ' chloro-, 5,7 dihydroxyl-6,8-dimethyl-flavanone):
With 200 milligrams of (0.001mol) 6-hydroxyl-2,4 hydroxyl-3,5 dimethyl acetophenones, 700 milligrams of (0.005mol) 4-chlorobenzaldehydes, 270 milligrams of (0.005mol) Hydrocerol As are dissolved in the small amount of ethanol, heat up in 200 ℃ stirring reaction 5 hours; Reactant is used dissolve with ethanol, get 25 milligrams of light green materials through column chromatography, yield 12.5%, HNMR (500MHz, DMSO), δ 7.56 (2H, d; J=8.4Hz, H-e), 7.51 (2H, d, J=8.5Hz, H-d), 5.58 (1H; Dd, J=12.3,2.7Hz, H-c), 3.18 (1H, dd; J=17.0,12.5Hz, H-b2), 2.86 (1H, dd, J=17.0; 3.0Hz, H-b1), 1.97 (6H, d, J=4.5Hz, H-a) ESI-MS (m/z): [M-1]-=317.
Embodiment 3: and compound 1-n:2-(furans-2-yl)-5,7-dihydroxyl-6,8-methyl-chromanone
With 200 milligrams of (0.001mol) 6-hydroxyl-2,4 hydroxyl-3,5 dimethyl acetophenones; 0.3ml (0.0015mol) furfural, 250 milligrams of (0.004mol) tartrate are dissolved in a small amount of glyceryl alcohol, heat up in 50 ℃; Stirring reaction 15 hours is used dissolve with ethanol with reactant, gets 35 milligrams of faint yellow materials through column chromatography; Yield 15%
HNMR(500MHz，DMSO)δ7.36(H，d，J＝8.4Hz，H-e)，6.26(H，d，J＝8.5Hz，H-d)，6.19(H，d，J＝8.5Hz，H-d)，5.74(1H，dd，J＝12.3，2.7Hz，H-c)，3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.85(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.99(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝257。
According to the synthetic following compounds of above-mentioned preparation method.
Embodiment 4: compound 1-c: the preparation of (6 ' chloro-, 5,7 dihydroxyl-6,8-dimethyl-flavanone):
HNMR(500MHz，DMSO)δ7.72(1H，d，J＝8.4Hz，H-d)，7.53(1H，d，J＝8.5Hz，H-d)，7.42(1H，d，J＝8.5Hz，H-d)，7.41(1H，dd，J＝7.6Hz，H-d)，5.58(1H，dd，J＝12.3，2.7Hz，H-c)3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.96(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝317。
Embodiment 5: compound 1-d: the preparation of (4 ' nitro-5,7 dihydroxyl-6,8-dimethyl-flavanone):
HNMR(500MHz，DMSO)，δ8.31(2H，d，J＝8.4Hz，H-e)，7.83(2H，d，J＝8.5Hz，H-d)，5.76(1H，dd，J＝12.3，2.7Hz，H-c)，3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.97(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.99(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝299
Embodiment 6: compound 1-e: the preparation of (6 ' nitro-5,7 dihydroxyl-6,8-dimethyl-flavanone)
HNMR(500MHz，DMSO)，δ8.02(1H，d，J＝8.4Hz，H-d)，7.89(1H，d，J＝8.5Hz，H-d)，7.85(1H，d，J＝8.5Hz，H-d)，7.70(1H，dd，J＝8.2Hz，H-d)，5.55(1H，dd，J＝12.3，2.7Hz，H-c)3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.96(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝299。
Embodiment 7: compound 1-f: the preparation of (4 ' hydroxyl, 6 ' methoxyl group-5,7 dihydroxyl-6,8-dimethyl-flavanone):
HNMR(500MHz，DMSO)，δ7.02(1H，d，J＝8.4Hz，H-d)，6.53(1H，d，J＝8.5Hz，H-d)，6.22(1H，d，s，H-d)5.52(1H，dd，J＝12.3，2.7Hz，H-c)，3.75(3H，d，s，H-a)3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.97(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝329。
Embodiment 8: compound 1-g: the preparation of (4 ' methoxyl group-5,7 dihydroxyl-6,8-dimethyl-flavanone):
HNMR(500MHz，DMSO)，δ7.06(2H，d，J＝8.4Hz，H-e)，6.89(2H，d，J＝8.5Hz，H-d)，5.56(1H，dd，J＝12.3，2.7Hz，H-c)，3.75(3H，d，s，H-a)，3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.83(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.97(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝313
Embodiment 9: compound 1-h: the preparation of (6 ' methoxyl group-5,7 dihydroxyl-6,8-dimethyl-flavanone):
HNMR(500MHz，DMSO)，δ7.12(1H，d，J＝8.4Hz，H-d)，7.05(1H，d，J＝8.5Hz，H-d)，6.85(1H，d，J＝8.5Hz，H-d)，6.78(1H，dd，J＝6.8Hz，H-d)，5.58(1H，dd，J＝12.3，2.7Hz，H-c)3.75(3H，d，s，H-a)，3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.96(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝313。
Embodiment 10: compound 1-i: the preparation of (4 ', 6 ' dimethoxy-5,7 dihydroxyl-6,8-dimethyl-flavanone):
HNMR(500MHz，DMSO)，δ7.03(1H，d，J＝8.4Hz，H-e)，6.28(1H，d，J＝8.5Hz，H-d)，6.21(1H，d，s，H-d)，5.56(1H，dd，J＝12.3，2.7Hz，H-c)，3.75(6H，d，s，H-a)3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.97(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝343。
Embodiment 11: compound 1-j: the preparation of (4 ', 6 ' dihydroxyl-5,7 dihydroxyl-6,8-dimethyl-flavanone):
HNMR(500MHz，DMSO)，δ6.89(1H，d，J＝8.4Hz，H-e)，6.26(1H，d，J＝8.5Hz，H-d)，6.20(1H，d，s，H-d)，5.58(1H，dd，J＝12.3，2.7Hz，H-c)，3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.97(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝315
Embodiment 12: compound 1-k: the preparation of (4 ', 5 ' dimethoxy-5,7 dihydroxyl-6,8-dimethyl-flavanone):
HNMR(500MHz，DMSO)，δ6.69(1H，d，J＝8.4Hz，H-e)，6.64(1H，d，s，H-d)，6.59(1H，d，J＝8.5Hz，H-d)，5.58(1H，dd，J＝12.3，2.7Hz，H-c)，3.75(6H，d，s，H-a)3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.97(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝343。
Embodiment 13: compound 1-l: the preparation of (4 ', 5 ' dihydroxyl-5,7 dihydroxyl-6,8-dimethyl-flavanone):
HNMR(500MHz，DMSO)，δ6.89(1H，d，J＝8.4Hz，H-e)，6.67(1H，d，s，H-d)，6.61(1H，d，J＝8.5Hz，H-d)5.58(1H，dd，J＝12.3，2.7Hz，H-c)，3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.97(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝315。
Embodiment 14: compound 1-m: the preparation of (4 ', 6 ' two chloro-5,7 dihydroxyl-6,8-dimethyl-flavanone):
HNMR(500MHz，DMSO)，δ7.46(1H，d，J＝8.4Hz，H-e)，7.21(1H，d，J＝8.5Hz，H-d)，7.18(1H，d，s，H-d)5.58(1H，dd，J＝12.3，2.7Hz，H-c)，3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.97(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝353
Embodiment 15: compound 1-o: the preparation of (4 ' hydroxyl-5,7 dihydroxyl-6,8-dimethoxy flavanone):
HNMR(500MHz，DMSO)，δ7.46(2H，d，J＝8.4Hz，H-e)，7.21(2H，d，J＝8.5Hz，H-d)，5.58(1H，dd，J＝12.3，2.7Hz，H-c)，3.73(6H，s，H-a)3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.97(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝331
Embodiment 16: compound 1-p: the preparation of (4 ' amino-5,7 dihydroxyl-6,8-dimethoxy flavanone):
HNMR(500MHz，DMSO)，δ7.46(2H，d，J＝8.4Hz，H-e)，7.21(2H，d，J＝8.5Hz，H-d)，5.58(1H，dd，J＝12.3，2.7Hz，H-c)，3.73(6H，s，H-a)3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.97(6H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝331
Embodiment 17: compound 1-q: the preparation of (4 ' methyl-5,7 dihydroxyl-6,8-dimethoxy flavanone):
HNMR(500MHz，DMSO)，δ6.82(2H，d，J＝8.4Hz，H-e)，6.34(2H，d，J＝8.5Hz，H-d)，5.58(1H，dd，J＝12.3，2.7Hz，H-c)，4.21(2H，s，H-f)，3.73(6H，s，H-a)3.18(1H，dd，J＝17.0，12.5Hz，H-b 2)，2.86(1H，dd，J＝17.0，3.0Hz，H-b 1)，1.97(9H，d，J＝4.5Hz，H-a)ESI-MS(m/z)：[M-1] -＝297
Embodiment 18: compound 1-r: the preparation of (5,7 dihydroxyl-6 methyl-8-allyl group flavanone):
HNMR(500MHz，DMSO)，δ7.25(1H，s，H-j)，7.03(4H，d，J＝8.8Hz，H-i)，6.58(1H，s，，H-h)6.30(1H，d，J＝7.8Hz，H-g)5.58(1H，dd，J＝12.3，2.7Hz，H-f)，4.94(2H，s，H-e)，3.73(6H，s，H-d)3.22(2H，s，，H-b)，3.18(1H，dd，J＝17.0，12.5Hz，H-c2)，2.86(1H，dd，J＝17.0，3.0Hz，H-c1)，1.97(3H，s，，H-a)ESI-MS(m/z)：[M-1]-＝309

Claims (1)

1. the application of flavanone derivatives in the preparation anti-cardiovascular disease, the structure of this verivate is following:
Figure FSB00000691851400011
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0122053A2 (en) * 1983-03-10 1984-10-17 Inverni Della Beffa S.P.A. Pharmaceutical compositions containing compounds with a flavanone skeleton and process for the preparation of said compounds

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0122053A2 (en) * 1983-03-10 1984-10-17 Inverni Della Beffa S.P.A. Pharmaceutical compositions containing compounds with a flavanone skeleton and process for the preparation of said compounds

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Jinyong Peng, et al.Preparative isolation of four new and two known flavonoids from the leaf of Patrinia villosa Juss. by counter-current chromatography and evaluation of their anticancer activities in vitro.《Journal of Chromatography A》.2006,第1115卷103-111. *
wing lai chan, et al.One step synthesis of polyhydroxyflavanones from hydroxyacetophenones and hydroxybenzaldehydes.《Heterocycles》.1996,第43卷(第3期),551-554. *

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