CN105085219B - A ring has the quinoid chalcone compound of isopentene group, preparation method and anti-inflammatory activity - Google Patents
A ring has the quinoid chalcone compound of isopentene group, preparation method and anti-inflammatory activity Download PDFInfo
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- CN105085219B CN105085219B CN201410220017.8A CN201410220017A CN105085219B CN 105085219 B CN105085219 B CN 105085219B CN 201410220017 A CN201410220017 A CN 201410220017A CN 105085219 B CN105085219 B CN 105085219B
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Abstract
The invention discloses a kind of A rings to have quinoid chalcone compounds of isopentene group and preparation method thereof and anti-inflammatory activity application.The compound of the present invention has structure shown in general formula (I); preparation method includes the following steps: (1) synthesizing 3; 5- dihydroxy -2- acetyl group -6; 6- diisoamyl alkenyl hexamethylene -2; 4- dienone; (2) 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6 is synthesized; 6- diisoamyl alkenyl hexamethylene -2; 4- dienone; (3) a kind of A ring of synthesis methoxy methoxy base protection has the quinoid chalcone compounds of isopentene group, and (4) synthesize the quinoid chalcone compounds that one kind A ring has isopentene group.The compound of the present invention preparation method is simple and has apparent anti-inflammatory effect.
Description
Technical field
The present invention relates to pharmaceutical technology field, a kind of A ring has the compound of the quinoid chalcone structure of isopentene group, system
Preparation Method, and the pharmaceutical composition containing them and its application in anti-inflammatory.
Background technique
Blood vessel endothelium injury refers to vascular endothelial cell because broken by factors such as physics, chemistry, ray, cell factor and bacteriums
Badly there is direct or indirect damage.After impaired vascular endothelium, damage part not only loses the effect of endothelial barrier, simultaneously
Cytokine profiles can be also generated, intense stimulus and induction generate a large amount of Inos (iNOS), and iNOS is fast
Speed expression, and it is catalyzed the NO for generating 1000 times of normal physiological amounts, the NO largely generated is in conjunction with oxygen molecule or peroxide, respectively
Form the oxygen radical ROS (OONO with strong oxidizing property function-) or RNS (NO2, N2O3) carry out performance cytotoxicity.One side
Face, these free radicals make sulfydryl albumen and lipid peroxidation, aggravate endothelial injuries and lipidosis；On the other hand, these oxygen from
Can be acted on by same amino by base, the fracture of DNA circle, exhaust glutathione deposit to induce the damage of DNA, to promote again
Aggravate inflammation occurrence and development and cellular damage.Meanwhile iNOS activity can maintain a few hours to a couple of days, therefore can cause to damage for a long time
Wound effect, leads to vasomotor disturbance, disturbance of blood coagulation, hemodynamic responses, and severe one may occur in which the organic change of damaged blood vessels,
And thus cause a series of cardiovascular and cerebrovascular related diseases, such as coronary heart disease, secondary thrombus are formed, artery sclerosis.These diseases
Often there is irreversibility, once occurring, be difficult to eradicate, bring very big difficulty to clinical treatment, curative effect is also by very big shadow
It rings.Therefore inhibit iNOS activity, can reduce the primary and secondary of inflammation, reduce the diseases related morbidity of blood vessel endothelium injury
Rate protects cardiovascular and cerebrovascular.
Quinoid chalcone compounds belong to flavone compound, and such compound negligible amounts in natural resources are
The main component of traditional Chinese medicine safflower water soluble ingredient carthamin yellow, representation compound are hydroxyl radical carthamin yellow carthamus A.Hydroxyl
Carthamus tinctorius yellow colour A is considered as the principle active component of safflower, research shows that hydroxyl radical carthamin yellow carthamus A can by inhibit inflammation,
Damage of the hypoxia to vascular endothelial cell is reduced, ischemic neuron degeneration necrosis and gliosis are mitigated, is prevented and treated
Blood vessel and neuroinflammatory conditions and blood vessel endothelium injury related disease.But hydroxyl radical carthamin yellow carthamus A physics, chemical property are unstable
It is fixed, under light, heat, acid-base condition, easily it is destroyed, it is not easy to maintain, it limits it and further develops and uses.
Do not go deep into still also about the relevant synthesis of quinoid chalcone and pharmacological research at present, effectively to illustrate traditional Chinese medicine
Mechanism of action, and preferably anti-inflammatory drug provides theoretical foundation and practical experience to find activity, we have synthesized a kind of A ring tool
There is the quinoid chalcone of isopentene group, and its anti-inflammatory activity is evaluated.
Summary of the invention
The object of the present invention is to provide the quinoid chalcone compounds that a kind of A ring has isopentene group.
Another object of the present invention is to provide the methods of the preparation of such compound.
A further object of the present invention is to provide a kind of pharmaceutical compositions comprising a kind of A ring of effective dose has different
The quinoid chalcone compounds and pharmaceutical carrier and/or excipient of pentenyl.
Another object of the present invention is to provide a kind of A ring preparing with the quinoid chalcone compounds of isopentene group
For treat and/or the drug or health care product of prevention of inflammation in application.
The invention provides the following technical scheme:
First aspect present invention provides the quinoid chalcone that one kind A ring has isopentene group, which is characterized in that has general formula
(I) structure shown in:
Wherein, R is 1,2,3,4 arbitrary substituent groups on phenyl ring,
The position of one substituent group are as follows:
Two substitutionsThe position of base are as follows:
The position of three substituent groups are as follows:
The position of four substituent groups are as follows:
Wherein R is selected from: hydrogen, hydroxyl, sulfydryl, methoxyl group, amino, nitro, halogen, cyano, methylsulphur acidic group, formyl.
In the compound, R preferably is selected from: hydrogen, hydroxyl, methoxyl group, chlorine, bromine.
The compound preferably is selected from following compound:
Second aspect of the present invention provides the preparation method with general formula (I) structural compounds, which is characterized in that including with
Lower step:
(1) synthesis of 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
2,4,6- trihydroxy-acetophenones are taken to be added in aqueous alkali, ice-water bath stirring and dissolving takes 2 times 2,4,6- trihydroxy benzenes
The bromo iso-amylene alkane of ethyl ketone mole, is added in aqueous solution；After sixty minutes, PH to 3 is adjusted with dilute hydrochloric acid, then uses acetic acid second
The washing of its organic phase, drying are finally used petrol ether/ethyl acetate mixed solvent volume ratio 10:1, silica gel column chromatography by ester extraction
Obtain yellow oil 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone.
(2) synthesis of 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone is taken to be added in anhydrous propanone,
After stirring and dissolving, the carbon of 7.4 times of 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone moles is taken
Sour potassium after stirring 15 minutes, then takes 2.5 times of 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienones
The chloromethyl methyl ether of mole is added dropwise in acetone soln, and after stirring 5 hours, filtering is dry by its filtrate, finally uses petroleum
Ether/ethyl acetate mixed solvent volume ratio 20:1, silica gel column chromatography obtain yellow oil 3- hydroxy-5-methyl oxygen methoxyl group -2-
Acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone.
(3) a kind of A ring of methoxy methoxy base protection has the synthesis of the quinoid chalcone compounds of isopentene group
Take 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone and substituted benzene
Formaldehyde is added ethanol water dissolution, is added 2.5 times of 3- hydroxy-5-methyl oxygen methoxyl group -2- second with molar ratio 1:1.5 mixing
The potassium hydroxide of acyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone mole is adjusted after normal-temperature reaction 3 days with dilute hydrochloric acid
PH to 3, is then extracted with ethyl acetate, and by the washing of its organic phase, drying, finally uses methanol/water mixed solvent volume ratio 7:3,
YMC Rp-C18Column chromatographs to obtain quinoid chalcone compounds of a kind of A ring with isopentene group of methoxy methoxy base protection.
(4) one kind A ring has the synthesis of the quinoid chalcone compounds of isopentene group
There are a kind of A ring for taking methoxy methoxy base to protect the quinoid chalcone compounds of isopentene group tetrahydrofuran is added
After dissolution, dilute hydrochloric acid is added, heating reaction 10 hours after reactant is cooled to room temperature, is poured into water, then uses acetic acid
The washing of its organic phase, drying are finally used methanol/water mixed solvent volume ratio 6:4, YMC Rp-C by ethyl ester extraction18Column chromatographs
There are the quinoid chalcone compounds of isopentene group to a kind of A ring.
Wherein, R signified in preparation method is identical with above-mentioned restriction, is preferably selected from hydroxyl, sulfydryl, methoxyl group, amino,
Nitro, halogen, cyano, methylsulphur acidic group, formyl；More preferably from hydroxyl, methoxyl group, chlorine, bromine.
Third aspect present invention be related to a kind of compound as described in general formula (I) each situation containing medicine effective dose and
The pharmaceutical composition of pharmaceutically acceptable carrier.
The invention further relates to containing as the compounds of this invention and customary pharmaceutical excipients of active ingredient or the medicine of adjuvant
Compositions.Usual pharmaceutical composition of the present invention contains the compounds of this invention of 0.1~95% weight.This hair in unit dosage form
The bright general content of compound is 0.1~100mg, and preferred unit dosage form contains 4~50mg.
The pharmaceutical composition of the compounds of this invention can be prepared according to method well known in the art.When for this purpose, if
It needs, can be by the compounds of this invention in conjunction with one or more solids or liquid pharmaceutical excipients and/or adjuvant, being made can be used as
The administration form or dosage form appropriate that people's medicine or veterinary drug use.
The compounds of this invention can be administered in a unit containing its pharmaceutical composition, and administration route can be enteron aisle
Or non-bowel, such as oral, muscle, subcutaneous, nasal cavity, oral mucosa, skin, peritonaeum or rectum.The compounds of this invention contains
The administration route of its pharmaceutical composition can be drug administration by injection.Injection includes intravenous injection, intramuscular injection, subcutaneous injection, intradermal
Injection and acupoint injection therapy etc..
Form of administration can be liquid dosage form, solid dosage forms.As liquid dosage form can be true solution class, colloidal type, particle
Dosage form, emulsion dosage form, mixed suspension form.Other dosage forms such as tablet, dripping pill, aerosol, pill, pulvis, solution, mixes capsule
Suspension, emulsion, granule, suppository, freeze drying powder injection etc..
The compounds of this invention can be made ordinary preparation, be also possible to sustained release preparation, controlled release preparation, targeting preparation and various
Particulate delivery system.
Such as in order to which tablet is made in unit dosage forms for administration, various carriers well known in the art can be widely used.About
The example of carrier is, such as diluent and absorbent, such as starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, Portugal
Grape sugar, urea, calcium carbonate, white bole, microcrystalline cellulose, alumina silicate etc.；Wetting agent and adhesive, such as water, glycerol, poly- second two
Alcohol, ethyl alcohol, propyl alcohol, starch slurry, dextrin, syrup, honey, glucose solution, mucialga of arabic gummy, gelatine size, carboxymethyl cellulose
Sodium, lac, methylcellulose, potassium phosphate, polyvinylpyrrolidone etc.；Disintegrating agent, such as dry starch, alginate, agar
Powder, laminaran, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene sorbitol aliphatic ester, dodecyl sodium sulfate,
Methylcellulose, ethyl cellulose etc.；Disintegration inhibitor, such as sucrose, glyceryl tristearate, cocoa butter, hydrogenated oil and fat etc.；It inhales
Receive promotor, such as quaternary ammonium salt, lauryl sodium sulfate etc.；Lubricant, such as talcum powder, silica, cornstarch, tristearin
Hydrochlorate, boric acid, atoleine, polyethylene glycol etc..Tablet can also be further made to coating tablet, such as sugar coated tablet, film
Coating tablet, enteric coated tablets or double-layer tablets and multilayer tablet.
Such as in order to which pill is made in administration unit, various carriers well known in the art can be widely used.About carrier
Example be such as diluent and absorbent, such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, polyvinylpyrrolidine
Ketone, single stearic acid glycerine lipoprotein, kaolin, talcum powder etc.；Adhesive, such as Arabic gum, bassora gum, gelatin, ethyl alcohol, honey, liquid
Sugar, rice paste or batter etc.；Disintegrating agent, such as agar powder, dry starch, alginate, dodecyl sodium sulfate, methylcellulose,
Ethyl cellulose etc..
Such as in order to which capsule is made in administration unit, effective component the compounds of this invention and above-mentioned various carriers are mixed
It closes, and thus obtained mixture is placed in hard gelatine capsule or soft capsule.It can also be by effective component the compounds of this invention
Microcapsules is made, is suspended in aqueous medium and forms suspension, also can be fitted into hard capsule or be made injection application.
For example, injection preparation is made in the compounds of this invention, such as solution, suspension solution, emulsion, freeze-dried powder
Agent, this preparation can be aqueous or non-aqueous, can contain acceptable carrier in a kind of and/or a variety of pharmacodynamics, diluent, viscous
Mixture, lubricant, preservative, surfactant or dispersing agent.As diluent can be selected from water, ethyl alcohol, polyethylene glycol, 1,3- the third two
Alcohol, the isooctadecanol of ethoxylation, polyoxygenated isooctadecanol, polyoxyethylene sorbitol rouge, fat acid esters etc..In addition, in order to make
Standby isotonic injection, can add suitable sodium chloride, glucose or glycerol, further, it is also possible to add into injection preparation
Conventional cosolvent, buffer, pH adjusting agent etc..These auxiliary materials are commonly used in the art.
In addition, if desired, can also be added into pharmaceutical preparation colorant, preservative, fragrance, corrigent, sweetener or
Other materials.
To reach medication purpose, enhance therapeutic effect, drug of the invention or pharmaceutical composition well known can be given with any
The administration of prescription method.
The dosage of the compounds of this invention pharmaceutical composition depends on many factors, such as to be prevented or be treated disease
Property and severity, gender, age, weight, personality and the individual reaction of patient or animal, administration route, administration number of times,
Therapeutic purposes, therefore therapeutic dose of the invention can have large-scale variation.In general, Chinese pharmacology ingredient of the present invention makes
It is well known to those skilled in the art with dosage.It can be according to the present invention contained in preparation last in compound composition
Actual drug quantity is subject to adjustment appropriate, to reach the requirement of its therapeutically effective amount, completes prevention or treatment mesh of the invention
's.The daily Suitable dosage ranges of the compounds of this invention: the dosage of the compound of the present invention is 0.001~100mg/Kg body
Weight, preferably 0.1~60mg/Kg weight, more preferably 1~30mg/Kg weight, most preferably 2~15mg/Kg weight.It is adult
The compounds of this invention that patient takes is 10~500mg daily, preferably 20~100mg, can once take or divide 2~3 clothes
With；The dosage of children taking is according to 5~30mg of every kg weight, preferably 10~20mg/kg weight.Above-mentioned dosage can be single dose
Amount form is divided into several, such as two, three or four dosage forms for administration, this is limited to the clinical experience of administration doctor and controls
The dosage regimen for the treatment of means.The compound of the present invention or composition can individually be taken, or with other treatment drug or symptomatic drugs
Merge and uses.
Fourth aspect present invention be related to a kind of A ring with isopentene group quinoid chalcone compounds prevention and/or
Treat the application in anti-inflammatory drugs or health care product.
Experiments have shown that a kind of A ring of the invention has the quinoid chalcone compounds of isopentene group in evaluation anti-inflammatory drug
The model of curative effect, the Turnover of Mouse Peritoneal Macrophages of LPS induction, which is secreted, shows apparent anti-inflammatory activity on NO inhibitory activity model,
And the experiment of macrophage appreciation rate shows that a kind of A ring of the invention has the quinoid chalcone compounds cell of isopentene group
Toxicity is lower.
A kind of A ring of the invention has the quinoid chalcone compounds of isopentene group can be significantly by inhibiting inductivity
Nitricoxide synthase (iNOS), reduces the generation of NO, to mitigate the inflammation damnification of blood vessel endothelium and nerve cell, clinically may be used
For treating the blood vessel and neuroinflammatory disorder and intercurrent disease of mammal and the mankind, such as vasculitis, osteoarthritis, neuritis
Disease, coronary heart disease, atherosclerosis.
The indication of the compound of the present invention and the pharmaceutical composition containing the compounds of this invention, mainly include blood vessel and
Neuroinflammatory disorder and immune inflammation disease, such as vasculitis, osteoarthritis, neuritis, rheumatic arthritis, tatanic ridge
Vertebra inflammation, scapulohumeral periarthritis, bursal synovitis, myotenositis.Furthermore the compounds of this invention pharmaceutical composition can also be treated because platelet aggregation causes
Blood vessel embolism, such as angina pectoris, atherosclerosis, myocardial infarction and cerebral infarction.
Effective technology effect
1. a kind of A ring of the invention has the quinoid chalcone compounds structure novel of isopentene group, it is showed no document
Report has the potentiality for being developed further into anti-inflammatory aspect new drug.
2. a kind of A ring of the invention has the quinoid chalcone compounds preparation method route of isopentene group novel, point
From simplicity.
3. a kind of A ring of the invention has preferable anti-inflammatory activity with the quinoid chalcone compounds of isopentene group,
It is 1 × 10 in concentration-5When mol/L, the compound has apparent anti-inflammatory effect, and it is 89.4~99.3% that NO, which generates inhibiting rate,
The anti-inflammatory activity of such compound is not shown in relevant report at present.
Specific embodiment
The following examples and pharmacological activity experiment are for further illustrating the present invention, but this does not imply that the present invention
Any restrictions.
1, one kind A ring has the preparation method of the quinoid chalcone compounds 1~9 of isopentene group
Embodiment 1
The synthetic method of compound 1, comprising the following steps:
(1) synthesis of 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1g2 is taken, 4,6- trihydroxy-acetophenones and 0.68g potassium hydroxide are added in 10ml water, and ice-water bath stirring and dissolving takes
1.37ml bromo iso-amylene, is added in aqueous solution；After sixty minutes, PH to 3 is adjusted with dilute hydrochloric acid, is then extracted with ethyl acetate,
By the washing of its organic phase, drying, petrol ether/ethyl acetate mixed solvent volume ratio 10:1 is finally used, silica gel column chromatography obtains
0.8g yellow oil 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone, yield 44%；It should
Following reaction occurs for process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,300MHz)δ1.641(12H,s,4×CH3),2.566
(5H,m,-CH2CH=,-CH3CO),2.660(2H,m,-CH2), CH=4.894 (2H, t, J=7.5Hz ,=CHCH2),5.661
(1H,s,H-4).ESI-MS:m/z303.1[M-H]+.
(2) synthesis of 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1.22g3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone is taken to be added to anhydrous third
In ketone, after stirring and dissolving, 4.09g potassium carbonate is taken, after stirring 15 minutes, then 760 μ l chloromethyl methyl ethers is taken to be added dropwise to acetone soln
In, after stirring 5 hours, filtering is dry by its filtrate, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 20:1, silica gel
Column chromatographs to obtain 1.07g yellow oil 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4-
Dienone, yield 77%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(CDCl3,300MHz)δ1.485(6H,s,2×CH3),1.501(6H,
s,2×CH3),2.408(2H,m,-CH2), CH=2.634 (2H, m ,-CH2), CH=3.393 (3H, s ,-OCH3),4.715
(2H, t, J=7.5Hz ,=CHCH2),5.071(2H,s,-OCH2O),5.679(1H,s,H-4).ESI-MS:m/z349.1[M+
H]+,371.1[M+Na]+.
(3) 2- (1- hydroxyl -3- phenyl-allylidene) -5- methoxy methoxy base -6,6- diisoamyl alkenyl hexamethylene -4-
The synthesis of alkene -1,3- diketone
Take 1.4g3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone with
The mixing of 2.8ml benzaldehyde is added ethanol water dissolution, adds 0.4g potassium hydroxide and use dilute hydrochloric acid after normal-temperature reaction 3 days
PH to 3 is adjusted, is then extracted with ethyl acetate, by the washing of its organic phase, drying, finally uses methanol/water mixed solvent volume ratio
7:3, YMC Rp-C18Column chromatographs to obtain 1.3g yellow oil 2- (1- hydroxyl -3- phenyl-allylidene) -5- methoxy methoxy
Base -6,6- diisoamyl alkenyl hexamethylene -4- alkene -1,3- diketone, yield 74%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,300MHz)δ1.562(12H,s,4×CH3),2.513
(2H,m,-CH2), CH=2.695 (2H, m ,-CH2), CH=3.467 (3H, s, OCH3), 4.849 (2H, t, J=7.8Hz ,=
CHCH2),5.328(2H,s,-OCH2O),5.876(1H,s,H-4),7.503(3H,m,H-3″,H-4″,H-5″),7.728(2H,
M, H-2 ", H-6 "), 7.914 (1H, d, J=15.9Hz, H-2 '), 8.280 (1H, d, J=15.9Hz, H-3 ')
13C NMR(DMSO-d6,125MHz)δ17.6(-CH3),25.4(-CH3),37.0(-CH2CH=), 56.7 (-
OCH3),57.6(C-6),95.1(-OCH2), O- 100.9 (C-4), 107.6 (C-2), 117.9 (- CH=C), 122.9 (C-2 '),
128.5 (C-2 ", C-6 "), 129.1 (C-3 ", C-5 "), 130.8 (C-4 "), 134.2 (- C=CH), 134.6 (C-1 "), 144.0
(C-3′),175.0(C-5),186.0(C-1′),190.8(C-3),195.7(C-1).
ESI-MS:m/z437.1[M+H]+.
(4) synthesis of 2- cinnamoyl -3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
Take 0.5g2- (1- hydroxyl -3- phenyl-allylidene) -5- methoxy methoxy base -6,6- diisoamyl alkenyl hexamethylene -
After the dissolution of 10ml tetrahydrofuran is added in 4- alkene -1,3- diketone, the 1M HCl of 10ml, heating reaction 10 hours, to reactant is added
After being cooled to room temperature, be poured into water, be then extracted with ethyl acetate, by its organic phase washing, dry, finally with methanol/
Water mixed solvent volume ratio 6:4, YMC Rp-C18Column chromatographs to obtain 0.23g yellow oil 2- cinnamoyl -3,5- dihydroxy -
6,6- diisoamyl alkenyl hexamethylene -2,4- dienones, yield 51%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,400MHz)δ1.511(12H,s,4×CH3),2.465
(2H,m,-CH2), CH=2.585 (2H, m ,-CH2), CH=4.798 (2H, t, J=7.6Hz ,=CHCH2),5.615(1H,s,
), H-4 7.441 (3H, m, H-3 ", H-4 ", H-5 "), 7.656 (2H, m, H-2 ", H-6 "), 7.791 (1H, d, J=15.9Hz, H-
2 '), 8.226 (1H, d, J=15.9Hz, H-3 ')
13C NMR(DMSO-d6,100MHz)δ17.7(-CH3),25.6(-CH3),37.0(-CH2), CH=57.5 (C-6),
99.9 (C-4), 107.2 (C-2), 118.2 (- CH=C), 123.6 (C-2 '), 128.4 (C-2 ", C-6 "), 129.1 (C-3 ", C-
), 5 " 130.6 (C-4 "), 134.0 (- C=CH), 134.9 (C-1 "), 143.1 (C-3 '), 179.9 (C-5), 185.6 (C-1 '),
190.7(C-3),196.3(C-1).
HR-ESI-MS:m/z393.2072[M+H]+,415.1887[M+Na]+.
Embodiment 2
The synthetic method of compound 2, comprising the following steps:
(1) synthesis of 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1g2 is taken, 4,6- trihydroxy-acetophenones and 0.68g potassium hydroxide are added in 10ml water, and ice-water bath stirring and dissolving takes
1.37ml bromo iso-amylene alkane, is added in aqueous solution；After sixty minutes, PH to 3 is adjusted with dilute hydrochloric acid, is then extracted with ethyl acetate
It takes, by the washing of its organic phase, drying, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 10:1, silica gel column chromatography obtains
0.8g yellow oil 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone, yield 44%；It should
Following reaction occurs for process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,300MHz)δ1.641(12H,s,4×CH3),2.566
(5H,m,-CH2CH=,-CH3CO),2.660(2H,m,-CH2), CH=4.894 (2H, t, J=7.5Hz ,=CHCH2),5.661
(1H,s,H-4).ESI-MS:m/z303.1[M-H]+.
(2) synthesis of 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1.22g3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone is taken to be added to anhydrous third
In ketone, after stirring and dissolving, 4.09g potassium carbonate is taken, after stirring 15 minutes, then 760 μ l chloromethyl methyl ethers is taken to be added dropwise to acetone soln
In, after stirring 5 hours, filtering is dry by its filtrate, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 20:1, silica gel
Column chromatographs to obtain 1.07g yellow oil 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4-
Dienone, yield 77%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(CDCl3,300MHz)δ1.485(6H,s,2×CH3),1.501(6H,
s,2×CH3),2.408(2H,m,-CH2), CH=2.634 (2H, m ,-CH2), CH=3.393 (3H, s ,-OCH3),4.715
(2H, t, J=7.5Hz ,=CHCH2),5.071(2H,s,-OCH2O),5.679(1H,s,H-4).ESI-MS:m/z349.1[M+
H]+,371.1[M+Na]+.
(3) 2- [1- hydroxyl -3- (4- chlorphenyl)-allylidene] -5- methoxy methoxy base -6,6- diisoamyl alkenyl ring
The synthesis of hex- 4- alkene -1,3- diketone
Take 1.4g3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone with
The mixing of 0.84g p-chlorobenzaldehyde is added ethanol water dissolution, adds 0.4g potassium hydroxide, after normal-temperature reaction 3 days, use is dilute
Hydrochloric acid adjusts PH to 3, is then extracted with ethyl acetate, and by the washing of its organic phase, drying, finally uses methanol/water mixed solvent body
Product is than 7:3, YMC Rp-C18Column chromatographs to obtain 1.47g yellow oil 2- [1- hydroxyl -3- (4- chlorphenyl)-Asia -2- propylene
Base] -5- methoxy methoxy base -6,6- diisoamyl alkenyl hexamethylene -4- alkene -1,3- diketone, yield 78%；The process occurs following anti-
It answers:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,300MHz)δ1.562(12H,s,4×CH3),2.521
(2H,m,-CH2), CH=2.699 (2H, m ,-CH2), CH=3.476 (3H, s, OCH3), 4.864 (2H, t, J=7.8Hz ,=
CHCH2),5.333(2H,s,-OCH2), O 5.894 (1H, s, H-4), 7.538 (2H, d, J=8.1Hz, H-3 ", H-5 "), 7.735
(2H, d, J=8.1Hz, H-2 ", H-6 "), 7.873 (1H, d, J=15.9Hz, H-2 '), 8.288 (1H, d, J=15.9Hz, H-
3′).
13C NMR(DMSO-d6,75MHz)δ17.6(-CH3),25.4(-CH3),37.1(-CH2CH=), 56.7 (-
OCH3),57.6(C-6),95.1(-OCH2), O- 101.0 (C-4), 107.6 (C-2), 117.9 (- CH=C), 123.6 (C-2 '),
129.1 (C-2 ", C-6 "), 130.0 (C-3 ", C-5 "), 133.6 (C-1 "), 134.2 (- C=CH), 135.3 (C-4 "), 142.5
(C-3′),175.0(C-5),185.9(C-1′),190.8(C-3),195.7(C-1).
ESI-MS:m/z471.2[M+H]+.
(4) synthesis of 2- (4- cinnamoyl chloride base) -3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
Take 0.47g2- [1- hydroxyl -3- (4- chlorphenyl)-allylidene] -5- methoxy methoxy base -6,6- diisoamyl alkene
After the dissolution of 10ml tetrahydrofuran is added in basic ring hex- 4- alkene -1,3- diketone, the 1M HCl of 10ml is added, heating is reacted 10 hours, to
It after reactant is cooled to room temperature, is poured into water, is then extracted with ethyl acetate, the washing of its organic phase, drying are finally used
Methanol/water mixed solvent volume ratio 6:4, YMC Rp-C18Column chromatographs to obtain 0.23g yellow oil 2- (4- cinnamoyl chloride base)-
3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- dienones, yield 53%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,300MHz)δ1.512(12H,s,4×CH3),2.457
(2H,m,-CH2), CH=2.565 (2H, m ,-CH2), CH=4.794 (2H, t, J=7.5Hz ,=CHCH2),5.568(1H,s,
), H-4 7.512 (2H, d, J=8.1Hz, H-3 ", H-5 "), 7.684 (2H, d, J=8.1Hz, H-2 ", H-6 "), 7.752 (1H,
D, J=15.9Hz, H-2 '), 8.205 (1H, d, J=15.9Hz, H-3 ')
13C NMR(DMSO-d6,125MHz)δ17.7(-CH3),25.6(-CH3),37.0(-CH2), CH=57.8 (C-6),
99.6 (C-4), 107.1 (C-2), 118.3 (- CH=C), 124.5 (C-2 '), 129.2 (C-2 ", C-6 "), 129.9 (C-3 ", C-
), 5 " 133.9 (- C=CH), 134.9 (C-1 ", C-4 "), 141.2 (C-3 '), 180.9 (C-5), 185.3 (C-1 '), 190.1
(C-3),196.5(C-1).
HR-ESI-MS:m/z427.1674[M+H]+,449.1497[M+Na]+.
Embodiment 3
The synthetic method of compound 3, comprising the following steps:
(1) synthesis of 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1g2 is taken, 4,6- trihydroxy-acetophenones and 0.68g potassium hydroxide are added in 10ml water, and ice-water bath stirring and dissolving takes
1.37ml bromo iso-amylene alkane, is added in aqueous solution；After sixty minutes, PH to 3 is adjusted with dilute hydrochloric acid, is then extracted with ethyl acetate
It takes, by the washing of its organic phase, drying, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 10:1, silica gel column chromatography obtains
0.8g yellow oil 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone, yield 44%；It should
Following reaction occurs for process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,300MHz)δ1.641(12H,s,4×CH3),2.566
(5H,m,-CH2CH=,-CH3CO),2.660(2H,m,-CH2), CH=4.894 (2H, t, J=7.5Hz ,=CHCH2),5.661
(1H,s,H-4).ESI-MS:m/z303.1[M-H]+.
(2) synthesis of 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1.22g3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone is taken to be added to anhydrous third
In ketone, after stirring and dissolving, 4.09g potassium carbonate is taken, after stirring 15 minutes, then 760 μ l chloromethyl methyl ethers is taken to be added dropwise to acetone soln
In, after stirring 5 hours, filtering is dry by its filtrate, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 20:1, silica gel
Column chromatographs to obtain 1.07g yellow oil 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4-
Dienone, yield 77%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(CDCl3,300MHz)δ1.485(6H,s,2×CH3),1.501(6H,
s,2×CH3),2.408(2H,m,-CH2), CH=2.634 (2H, m ,-CH2), CH=3.393 (3H, s ,-OCH3),4.715
(2H, t, J=7.5Hz ,=CHCH2),5.071(2H,s,-OCH2O),5.679(1H,s,H-4).ESI-MS:m/z349.1[M+
H]+,371.1[M+Na]+.
(3) 2- [1- hydroxyl -3- (4- methoxyphenyl)-allylidene] -5- methoxy methoxy base -6,6- diisoamyl alkene
The synthesis of basic ring hex- 4- alkene -1,3- diketone
Take 1.4g3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone and 610
The mixing of μ l P-methoxybenzal-dehyde is added ethanol water dissolution, adds 0.4g potassium hydroxide, after normal-temperature reaction 3 days, use is dilute
Hydrochloric acid adjusts PH to 3, is then extracted with ethyl acetate, and by the washing of its organic phase, drying, finally uses methanol/water mixed solvent body
Product is than 7:3, YMC Rp-C18Column chromatographs to obtain 1.23g yellow oil 2- [1- hydroxyl -3- (4- methoxyphenyl)-Asia -2- third
Alkenyl] -5- methoxy methoxy base -6,6- diisoamyl alkenyl hexamethylene -4- alkene -1,3- diketone, yield 66%；The process occurs as follows
Reaction:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,400MHz)δ1.499(12H,s,4×CH3),2.448
(2H,m,-CH2), CH=2.621 (2H, m ,-CH2), CH=3.404 (3H, s, CH3OCH2O),3.794(3H,s,ArOCH3),
4.793 (2H, t, J=7.5Hz ,=CHCH2),5.250(2H,s,-OCH2), O 5.796 (1H, s, H-4), 7.009 (2H, d, J=
8.4Hz, H-3 ", H-5 "), 7.644 (2H, d, J=8.4Hz, H-2 ", H-6 "), 7.848 (1H, d, J=15.6Hz, H-2 '),
8.146 (1H, d, J=15.6Hz, H-3 ')
13C NMR(DMSO-d6,100MHz)δ17.6(-CH3),25.5(-CH3),37.1(-CH2CH=), 55.3 (-
OCH3),56.7(CH3OCH2O),57.5(C-6),95.0(-OCH2O-),101.2(C-4),107.3(C-2),114.7(C-3″,
C-5 "), 118.0 (- CH=C), 120.0 (C-2 '), 127.3 (C-1 "), 130.5 (C-2 ", C-6 "), 134.1 (- C=CH),
144.5(C-3′),161.7(C-4″),174.5(C-5),185.8(C-1′),191.0(C-3),195.7(C-1).
ESI-MS:m/z467.1[M+H]+.
(4) 2- (4- methoxycinnamate acyl group) -3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone synthesizes
Take 0.46g2- [1- hydroxyl -3- (4- methoxyphenyl)-allylidene] -5- methoxy methoxy base -6,6- two different
After the dissolution of 10ml tetrahydrofuran is added in pentenyl hexamethylene -4- alkene -1,3- diketone, the 1M HCl of 10ml is added, heating reaction 10 is small
When, it after reactant is cooled to room temperature, is poured into water, is then extracted with ethyl acetate, its organic phase is washed, is dry,
Finally use methanol/water mixed solvent volume ratio 6:4, YMC Rp-C18Column chromatographs to obtain 0.22g yellow oil 2- (4- methoxyl group
Cinnamoyl) -3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone, yield 50%；The process occurs as follows
Reaction:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,400MHz)δ1.509(12H,s,4×CH3),2.454
(2H,m,-CH2), CH=2.574 (2H, m ,-CH2), CH=3.795 (3H, s, ArOCH3), 4.795 (2H, t, J=7.6Hz ,=
CHCH2), 5.588 (1H, s, H-4), 7.008 (2H, d, J=8Hz, H-3 ", H-5 "), 7.618 (2H, d, J=8Hz, H-2 ", H-
), 6 " 7.776 (1H, d, J=15.6Hz, H-2 '), 8.133 (1H, d, J=15.6Hz, H-3 ')
13C NMR(DMSO-d6,100MHz)δ17.7(-CH3),25.6(-CH3),37.0(-CH2CH=), 55.4 (-
OCH3), 57.4 (C-6), 100.0 (C-4), 106.9 (C-2), 114.7 (C-3 ", C-5 "), 118.3 (- CH=C), 120.8 (C-
2 '), 127.5 (C-1 "), 130.3 (C-2 ", C-6 "), 133.9 (- C=CH), 143.3 (C-3 '), 161.4 (C-4 "), 179.6
(C-5),185.5(C-1′),190.8(C-3),196.3(C-1).
HR-ESI-MS:m/z423.2178[M+H]+,445.1983[M+Na]+.
Embodiment 4
The synthetic method of compound 4, comprising the following steps:
(1) synthesis of 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1g2 is taken, 4,6- trihydroxy-acetophenones and 0.68g potassium hydroxide are added in 10ml water, and ice-water bath stirring and dissolving takes
1.37ml bromo iso-amylene alkane, is added in aqueous solution；After sixty minutes, PH to 3 is adjusted with dilute hydrochloric acid, is then extracted with ethyl acetate
It takes, by the washing of its organic phase, drying, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 10:1, silica gel column chromatography obtains
0.8g yellow oil 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone, yield 44%；It should
Following reaction occurs for process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,300MHz)δ1.641(12H,s,4×CH3),2.566
(5H,m,-CH2CH=,-CH3CO),2.660(2H,m,-CH2), CH=4.894 (2H, t, J=7.5Hz ,=CHCH2),5.661
(1H,s,H-4).ESI-MS:m/z303.1[M-H]+.
(2) synthesis of 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1.22g3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone is taken to be added to anhydrous third
In ketone, after stirring and dissolving, 4.09g potassium carbonate is taken, after stirring 15 minutes, then 760 μ l chloromethyl methyl ethers is taken to be added dropwise to acetone soln
In, after stirring 5 hours, filtering is dry by its filtrate, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 20:1, silica gel
Column chromatographs to obtain 1.07g yellow oil 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4-
Dienone, yield 77%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(CDCl3,300MHz)δ1.485(6H,s,2×CH3),1.501(6H,
s,2×CH3),2.408(2H,m,-CH2), CH=2.634 (2H, m ,-CH2), CH=3.393 (3H, s ,-OCH3),4.715
(2H, t, J=7.5Hz ,=CHCH2),5.071(2H,s,-OCH2O),5.679(1H,s,H-4).ESI-MS:m/z349.1[M+
H]+,371.1[M+Na]+.
(3) 2- [1- hydroxyl -3- (4- methoxy methoxy base phenyl)-allylidene] -5- methoxy methoxy base -6,6- two is different
The synthesis of pentenyl hexamethylene -4- alkene -1,3- diketone
Take 1.4g3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone and 1g
Methoxy methoxy benzaldehyde is mixed, ethanol water dissolution is added, adds 0.4g potassium hydroxide, after normal-temperature reaction 3 days, is used
Dilute hydrochloric acid adjusts PH to 3, is then extracted with ethyl acetate, and by the washing of its organic phase, drying, finally uses methanol/water mixed solvent
Volume ratio 7:3, YMC Rp-C18Column chromatographs to obtain 1.24g yellow oil 2- [1- hydroxyl -3- (4- methoxy methoxy base phenyl) -
Allylidene] -5- methoxy methoxy base -6,6- diisoamyl alkenyl hexamethylene -4- alkene -1,3- diketone, yield 62%；The process
Following reaction occurs:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,400MHz)δ1.505(12H,s,4×CH3),2.454
(2H,m,-CH2), CH=2.633 (2H, m ,-CH2), CH=3.373 (3H, s, CH3OCH2O),3.409(3H,s,CH3OCH2O),
4.792 (2H, t, J=7.6Hz ,=CHCH2),5.244(2H,s,-OCH2O),5.262(2H,s,-OCH2O),5.803(1H,s,
), H-4 7.098 (2H, d, J=8.4Hz, H-3 ", H-5 "), 7.643 (2H, d, J=8.4Hz, H-2 ", H-6 "), 7.848 (1H,
D, J=15.6Hz, H-2 '), 8.145 (1H, d, J=15.6Hz, H-3 ')
13C NMR(DMSO-d6,100MHz)δ17.6(-CH3),25.5(-CH3),37.1(-CH2), CH=55.7
(CH3OCH2O),56.7(CH3OCH2O),57.5(C-6),93.7(-OCH2O-),95.0(-OCH2O-),101.2(C-4),
107.4 (C-2), 116.6 (C-3 ", C-5 "), 118.0 (- CH=C), 120.6 (C-2 '), 128.2 (C-1 "), 130.4 (C-2 ",
C-6 "), 134.2 (- C=CH), 144.2 (C-3 '), 159.1 (C-4 "), 174.6 (C-5), 185.8 (C-1 '), 190.9 (C-
3),195.7(C-1).
ESI-MS:m/z497.2[M+H]+.
(4) synthesis of 2- (4- hydroxy cinnamate acyl group) -3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
Take 0.5g2- [1- hydroxyl -3- (4- methoxy methoxy base phenyl)-allylidene] -5- methoxy methoxy base -6,6- two
After the dissolution of 10ml tetrahydrofuran is added in isopentene group hexamethylene -4- alkene -1,3- diketone, the 1M HCl of 10ml, heating reaction 10 is added
Hour, it after reactant is cooled to room temperature, is poured into water, is then extracted with ethyl acetate, by the washing of its organic phase, do
It is dry, finally use methanol/water mixed solvent volume ratio 6:4, YMC Rp-C18Column chromatographs to obtain 0.2g yellow oil 2- (4- hydroxyl
Cinnamoyl) -3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone, yield 51%；The process occurs as follows
Reaction:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,400MHz)δ1.508(12H,s,4×CH3),2.450
(2H,m,-CH2), CH=2.562 (2H, m ,-CH2), CH=4.786 (2H, t, J=7.6Hz ,=CHCH2),5.571(1H,s,
), H-4 6.844 (2H, d, J=8.4Hz, H-3 ", H-5 "), 7.523 (2H, d, J=8Hz, H-2 ", H-6 "), 7.750 (1H, d, J
=15.6Hz, H-2 '), 8.091 (1H, d, J=15.6Hz, H-3 ')
13C NMR(DMSO-d6,100MHz)δ17.7(-CH3),25.6(-CH3),37.0(-CH2), CH=57.4 (C-6),
100.1 (C-4), 106.8 (C-2), 116.1 (C-3 ", C-5 "), 118.3 (- CH=C), 119.6 (C-2 '), 126.0 (C-1 "),
130.6 (C-2 ", C-6 "), 133.9 (- C=CH), 144.0 (C-3 '), 160.3 (C-4 "), 179.2 (C-5), 185.4 (C-
1′),190.8(C-3),196.2(C-1).
HR-ESI-MS:m/z409.2016[M+H]+,431.1841[M+Na]+.
Embodiment 5
The synthetic method of compound 5, comprising the following steps:
(1) synthesis of 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1g2 is taken, 4,6- trihydroxy-acetophenones and 0.68g potassium hydroxide are added in 10ml water, and ice-water bath stirring and dissolving takes
1.37ml bromo iso-amylene alkane, is added in aqueous solution；After sixty minutes, PH to 3 is adjusted with dilute hydrochloric acid, is then extracted with ethyl acetate
It takes, by the washing of its organic phase, drying, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 10:1, silica gel column chromatography obtains
0.8g yellow oil 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone, yield 44%；It should
Following reaction occurs for process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,300MHz)δ1.641(12H,s,4×CH3),2.566
(5H,m,-CH2CH=,-CH3CO),2.660(2H,m,-CH2), CH=4.894 (2H, t, J=7.5Hz ,=CHCH2),5.661
(1H,s,H-4).ESI-MS:m/z303.1[M-H]+.
(2) synthesis of 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1.22g3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone is taken to be added to anhydrous third
In ketone, after stirring and dissolving, 4.09g potassium carbonate is taken, after stirring 15 minutes, then 760 μ l chloromethyl methyl ethers is taken to be added dropwise to acetone soln
In, after stirring 5 hours, filtering is dry by its filtrate, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 20:1, silica gel
Column chromatographs to obtain 1.07g yellow oil 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4-
Dienone, yield 77%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(CDCl3,300MHz)δ1.485(6H,s,2×CH3),1.501(6H,
s,2×CH3),2.408(2H,m,-CH2), CH=2.634 (2H, m ,-CH2), CH=3.393 (3H, s ,-OCH3),4.715
(2H, t, J=7.5Hz ,=CHCH2),5.071(2H,s,-OCH2O),5.679(1H,s,H-4).ESI-MS:m/z349.1[M+
H]+,371.1[M+Na]+.
(3) 2- [1- hydroxyl -3- (4- methoxy methoxy base -3- methoxyphenyl)-allylidene] -5- methoxy methoxy base -
The synthesis of 6,6- diisoamyl alkenyl hexamethylene -4- alkene -1,3- diketone
Take 1.4g3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone with
1.27g4- methoxy methoxy base-m-methoxybenzaldehyde mixing, is added ethanol water dissolution, adds 0.4g potassium hydroxide, often
After temperature reaction 3 days, PH to 3 is adjusted with dilute hydrochloric acid, is then extracted with ethyl acetate, by the washing of its organic phase, drying, finally uses first
Alcohol/water mixed solvent volume ratio 7:3, YMC Rp-C18Column chromatographs to obtain 1.27g yellow oil 2- [1- hydroxyl -3- (4- methoxy
Methoxyl group -3- methoxyphenyl)-allylidene] -5- methoxy methoxy base -6,6- diisoamyl alkenyl hexamethylene -4- alkene -1,3- two
Ketone, yield 60%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,400MHz)δ1.509(12H,s,4×CH3),2.457
(2H,m,-CH2), CH=2.632 (2H, m ,-CH2), CH=3.385 (3H, s, CH3OCH2O),3.409(3H,s,CH3OCH2O),
3.831(3H,s,ArOCH3), 4.794 (2H, t, J=7.6Hz ,=CHCH2),5.226(2H,s,-OCH2O),5.260(2H,
s,-OCH2), O 5.806 (1H, s, H-4), 7.143 (1H, d, J=8.4Hz, H-5 "), 7.278 (2H, m, H-2 ", H-6 "),
7.851 (1H, d, J=15.6Hz, H-2 '), 8.128 (1H, d, J=15.6Hz, H-3 ')
13C NMR(DMSO-d6,100MHz)δ17.6(-CH3),25.5(-CH3),37.1(-CH2), CH=55.6
(OCH3),55.8(CH3OCH2O),56.7(CH3OCH2O),57.5(C-6),94.5(-OCH2O-),95.0(-OCH2O-),
101.2 (C-4), 107.4 (C-2), 112.1 (C-5 "), 116.1 (C-2 "), 118.0 (- CH=C), 120.8 (C-6 "), 122.1
(C-2 '), 128.9 (C-1 "), 134.2 (- C=CH), 144.6 (C-3 '), 148.6 (C-4 "), 149.8 (C-3 "), 174.6 (C-
5),185.8(C-1′),190.9(C-3),195.7(C-1).
ESI-MS:m/z527.1[M+H]+.
(4) 2- (4- hydroxy-3-methoxy cinnamoyl) -3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- diene
The synthesis of ketone
Take 0.53g2- [1- hydroxyl -3- (4- methoxy methoxy base -3- methoxyphenyl)-allylidene] -5- methoxy first
After the dissolution of 10ml tetrahydrofuran is added in oxygroup -6,6- diisoamyl alkenyl hexamethylene -4- alkene -1,3- diketone, the 1M HCl of 10ml is added,
Heating reaction 10 hours, after reactant is cooled to room temperature, is poured into water, is then extracted with ethyl acetate, its is organic
Mutually washing, drying, finally use methanol/water mixed solvent volume ratio 6:4, YMCRp-C18Column chromatographs to obtain 0.23g yellow oil
2- (4- hydroxy-3-methoxy cinnamoyl) -3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone, yield are
52%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,400MHz)δ1.512(12H,s,4×CH3),2.455
(2H,m,-CH2), CH=2.564 (2H, m ,-CH2), CH=3.816 (3H, s, OCH3), 4.792 (2H, t, J=7.6Hz ,=
CHCH2), 5.557 (1H, s, H-4), 6.858 (1H, d, J=8Hz, H-5 "), 7.180 (2H, m, H-2 ", H-6 "), 7.755
(1H, d, J=15.6Hz, H-2 '), 8.081 (1H, d, J=15.6Hz, H-3 ')
13C NMR(DMSO-d6,100MHz)δ17.7(-CH3),25.6(-CH3),37.0(-CH2), CH=55.6
(OCH3), 57.5 (C-6), 100.0 (C-4), 106.9 (C-2), 112.1 (C-5 "), 116.0 (C-2 "), 118.4 (- CH=C),
119.9 (C-6 "), 122.9 (C-2 '), 126.5 (C-1 "), 133.8 (- C=CH), 144.2 (C-3 '), 148.0 (C-4 "),
149.9(C-3″),179.7(C-5),185.4(C-1′),190.7(C-3),196.3(C-1).
HR-ESI-MS:m/z439.2124[M+H]+,461.1939[M+Na]+.
Embodiment 6
The synthetic method of compound 6, comprising the following steps:
(1) synthesis of 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1g2 is taken, 4,6- trihydroxy-acetophenones and 0.68g potassium hydroxide are added in 10ml water, and ice-water bath stirring and dissolving takes
1.37ml bromo iso-amylene alkane, is added in aqueous solution；After sixty minutes, PH to 3 is adjusted with dilute hydrochloric acid, is then extracted with ethyl acetate
It takes, by the washing of its organic phase, drying, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 10:1, silica gel column chromatography obtains
0.8g yellow oil 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone, yield 44%；It should
Following reaction occurs for process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,300MHz)δ1.641(12H,s,4×CH3),2.566
(5H,m,-CH2CH=,-CH3CO),2.660(2H,m,-CH2), CH=4.894 (2H, t, J=7.5Hz ,=CHCH2),5.661
(1H,s,H-4).ESI-MS:m/z303.1[M-H]+.
(2) synthesis of 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1.22g3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone is taken to be added to anhydrous third
In ketone, after stirring and dissolving, 4.09g potassium carbonate is taken, after stirring 15 minutes, then 760 μ l chloromethyl methyl ethers is taken to be added dropwise to acetone soln
In, after stirring 5 hours, filtering is dry by its filtrate, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 20:1, silica gel
Column chromatographs to obtain 1.07g yellow oil 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4-
Dienone, yield 77%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(CDCl3,300MHz)δ1.485(6H,s,2×CH3),1.501(6H,
s,2×CH3),2.408(2H,m,-CH2), CH=2.634 (2H, m ,-CH2), CH=3.393 (3H, s ,-OCH3),4.715
(2H, t, J=7.5Hz ,=CHCH2),5.071(2H,s,-OCH2O),5.679(1H,s,H-4).ESI-MS:m/z349.1[M+
H]+,371.1[M+Na]+.
(3) 2- [1- hydroxyl -3- (3,4,5- trimethoxyphenyl)-allylidene] -5- methoxy methoxy base -6,6- two
The synthesis of isopentene group hexamethylene -4- alkene -1,3- diketone
Take 1.4g3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone with
1.18g3, the mixing of 4,5- trimethoxybenzaldehyde are added ethanol water dissolution, add 0.4g potassium hydroxide, normal-temperature reaction 3
After it, PH to 3 is adjusted with dilute hydrochloric acid, is then extracted with ethyl acetate, it is finally mixed with methanol/water by the washing of its organic phase, drying
Bonding solvent volume ratio 7:3, YMC Rp-C18Column chromatographs to obtain 0.95g yellow oil 2- [1- hydroxyl -3- (3,4,5- trimethoxy
Phenyl)-allylidene] -5- methoxy methoxy base -6,6- diisoamyl alkenyl hexamethylene -4- alkene -1,3- diketone, yield 45%；
Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,400MHz)δ1.512(12H,s,4×CH3),2.458
(2H,m,-CH2), CH=2.627 (2H, m ,-CH2), CH=3.408 (3H, s, CH3OCH2O),3.716(3H,s,ArOCH3),
3.826(6H,s,2×ArOCH3), 4.790 (2H, t, J=7.6Hz ,=CHCH2),5.264(2H,s,-OCH2O),5.811
(1H, s, H-4), 6.998 (2H, s, H-2 ", H-6 "), 7.833 (1H, d, J=15.6Hz, H-2 '), 8.103 (1H, d, J=
15.6Hz,H-3′).
13C NMR(DMSO-d6,100MHz)δ17.6(-CH3),25.5(-CH3),37.1(-CH2), CH=55.9
(ArOCH3),56.7(CH3OCH2O),57.6(C-6),60.1(ArOCH3),95.1(-OCH2O-),101.1(C-4),106.1
(C-2 ", C-6 "), 107.6 (C-2), 118.0 (- CH=C), 121.9 (C-2 '), 130.2 (C-1 "), 134.2 (- C=CH),
140.2(C-4′),144.7(C-3′),153.2(C-3″,C-5″),174.8(C-5),185.8(C-1′),190.9(C-3),
195.7(C-1).
ESI-MS:m/z527.2[M+H]+.
(4) 2- (3,4,5- trimethoxy cinnamoyl) -3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- diene
The synthesis of ketone
0.53g2- [1- hydroxyl -3- (3,4,5- trimethoxyphenyl)-allylidene] -5- methoxy methoxy base -6 are taken,
After the dissolution of 10ml tetrahydrofuran is added in 6- diisoamyl alkenyl hexamethylene -4- alkene -1,3- diketone, the 1M HCl of 10ml is added, heating is anti-
It answers 10 hours, after reactant is cooled to room temperature, is poured into water, is then extracted with ethyl acetate, its organic phase is washed,
It is dry, finally use methanol/water mixed solvent volume ratio 6:4, YMC Rp-C18Column chromatograph to obtain 0.25g yellow oil 2- (3,4,
5- trimethoxy cinnamoyl) -3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone, yield 51%；The mistake
Cheng Fasheng reacts as follows:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,400MHz)δ1.516(12H,s,4×CH3),2.460
(2H,m,-CH2), CH=2.570 (2H, m ,-CH2), CH=3.705 (3H, s, OCH3),3.821(6H,s,2×OCH3),
4.788 (2H, t, J=7.6Hz ,=CHCH2),5.596(1H,s,H-4),6.974(2H,s,H-2″,H-6″),7.759(1H,
D, J=15.6Hz, H-2 '), 8.092 (1H, d, J=15.6Hz, H-3 ')
13C NMR(DMSO-d6,100MHz)δ17.7(-CH3),25.6(-CH3),37.0(-CH2), CH=55.9
(ArOCH3),57.5(C-6),60.2(ArOCH3),99.9(C-4),105.9(C-2″,C-6″),107.1(C-2),118.3(-
), CH=C 122.6 (C-2 '), 130.4 (C-1 "), 133.9 (- C=CH), 139.9 (C-4 '), 143.5 (C-3 '), 153.2 (C-
3″,C-5″),179.8(C-5),185.4(C-1′),190.7(C-3),196.3(C-1)
HR-ESI-MS:m/z483.2383[M+H]+,505.2204[M+Na]+.
Embodiment 7
The synthetic method of compound 7, comprising the following steps:
(1) synthesis of 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1g2 is taken, 4,6- trihydroxy-acetophenones and 0.68g potassium hydroxide are added in 10ml water, and ice-water bath stirring and dissolving takes
1.37ml bromo iso-amylene alkane, is added in aqueous solution；After sixty minutes, PH to 3 is adjusted with dilute hydrochloric acid, is then extracted with ethyl acetate
It takes, by the washing of its organic phase, drying, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 10:1, silica gel column chromatography obtains
0.8g yellow oil 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone, yield 44%；It should
Following reaction occurs for process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,300MHz)δ1.641(12H,s,4×CH3),2.566
(5H,m,-CH2CH=,-CH3CO),2.660(2H,m,-CH2), CH=4.894 (2H, t, J=7.5Hz ,=CHCH2),5.661
(1H,s,H-4).ESI-MS:m/z303.1[M-H]+.
(2) synthesis of 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
1.22g3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone is taken to be added to anhydrous third
In ketone, after stirring and dissolving, 4.09g potassium carbonate is taken, after stirring 15 minutes, then 760 μ l chloromethyl methyl ethers is taken to be added dropwise to acetone soln
In, after stirring 5 hours, filtering is dry by its filtrate, finally uses petrol ether/ethyl acetate mixed solvent volume ratio 20:1, silica gel
Column chromatographs to obtain 1.07g yellow oil 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4-
Dienone, yield 77%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(CDCl3,300MHz)δ1.485(6H,s,2×CH3),1.501(6H,
s,2×CH3),2.408(2H,m,-CH2), CH=2.634 (2H, m ,-CH2), CH=3.393 (3H, s ,-OCH3),4.715
(2H, t, J=7.5Hz ,=CHCH2),5.071(2H,s,-OCH2O),5.679(1H,s,H-4).ESI-MS:m/z349.1[M+
H]+,371.1[M+Na]+.
(3) 2- [1- hydroxyl -3- (4- bromophenyl)-allylidene] -5- methoxy methoxy base -6,6- diisoamyl alkenyl ring
The synthesis of hex- 4- alkene -1,3- diketone
Take 1.4g3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone with
The mixing of 1.09g p-bromobenzaldehyde is added ethanol water dissolution, adds 0.4g potassium hydroxide, after normal-temperature reaction 3 days, use is dilute
Hydrochloric acid adjusts PH to 3, is then extracted with ethyl acetate, and by the washing of its organic phase, drying, finally uses methanol/water mixed solvent body
Product is than 7:3, YMC Rp-C18Column chromatographs to obtain 1.57g yellow oil 2- [1- hydroxyl -3- (4- bromophenyl)-Asia -2- propylene
Base] -5- methoxy methoxy base -6,6- diisoamyl alkenyl hexamethylene -4- alkene -1,3- diketone, yield 76%；The process occurs following anti-
It answers:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,400MHz)δ1.501(12H,s,4×CH3),2.457
(2H,m,-CH2), CH=2.623 (2H, m ,-CH2), CH=3.409 (3H, s, CH3OCH2O), 4.784 (2H, t, J=7.6Hz,
=CHCH2),5.276(2H,s,-OCH2), O 5.821 (1H, s, H-4), 7.619 (2H, d, J=8.4Hz, H-3 ", H-5 "),
7.655 (1H, d, J=8.4Hz, H-2 ", H-6 "), 7.812 (1H, d, J=16Hz, H-2 '), 8.209 (1H, d, J=16Hz, H-
3′).
13C NMR(DMSO-d6,100MHz)δ17.6(-CH3),25.4(-CH3),37.1(-CH2), CH=56.7
(CH3OCH2O),57.6(C-6),95.1(-OCH2), O- 100.9 (C-4), 107.6 (C-2), 117.9 (- CH=C), 123.7
(C-2 '), 124.2 (C-4 ") 130.2 (C-2 ", C-6 "), 132.0 (C-3 ", C-5 "), 133.9 (C-1 "), 134.2 (- C=
CH),142.5(C-3′),175.0(C-5),185.8(C-1′),190.8(C-3),195.7(C-1).
ESI-MS:m/z537.1[M+Na]+.
(4) synthesis of 2- (4- cinnamyl bromide acyl group) -3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
Take 0.51g2- [1- hydroxyl -3- (4- bromophenyl)-allylidene] -5- methoxy methoxy base -6,6- diisoamyl alkene
After the dissolution of 10ml tetrahydrofuran is added in basic ring hex- 4- alkene -1,3- diketone, the 1M HCl of 10ml is added, heating is reacted 10 hours, to
It after reactant is cooled to room temperature, is poured into water, is then extracted with ethyl acetate, the washing of its organic phase, drying are finally used
Methanol/water mixed solvent volume ratio 6:4, YMC Rp-C18Column chromatographs to obtain 0.25g yellow oil 2- (4- cinnamyl bromide acyl group)-
3,5- dihydroxy -6,6- diisoamyl alkenyl hexamethylene -2,4- dienones, yield 54%；Following reaction occurs for the process:
The structural characterization data of product are as follows:1H NMR(DMSO-d6,400MHz)δ1.503(12H,s,4×CH3),2.457
(2H,m,-CH2), CH=2.566 (2H, m ,-CH2), CH=4.786 (2H, t, J=7.6Hz ,=CHCH2),5.604(1H,s,
), H-4 7.598 (2H, d, J=8.4Hz, H-3 ", H-5 "), 7.640 (1H, d, J=8.4Hz, H-2 ", H-6 "), 7.739 (1H,
D, J=15.6Hz, H-2 '), 8.213 (1H, d, J=15.6Hz, H-3 ')
13C NMR(DMSO-d6,100MHz)δ17.7(-CH3),25.6(-CH3),37.0(-CH2), CH=57.6 (C-6),
99.8 (C-4), 107.2 (C-2), 118.2 (- CH=C), 123.9 (C-2 '), 124.4 (C-4 ") 130.2 (C-2 ", C-6 "),
132.1 (C-3 ", C-5 "), 133.9 (C-1 "), 134.0 (- C=CH), 134.1 (- C=CH), 141.6 (C-3 '), 180.2.0
(C-5),185.4(C-1′),190.6(C-3),196.4(C-1).
HR-ESI-MS:m/z471.1172[M+H]+,493.0996[M+Na]+.
2, one kind A ring has the pharmacological activity experiment of the quinoid chalcone compounds of isopentene group
Find that above compound has the apparent anti-inflammatory effect experimental example 1 for inhibiting NO release screening by pharmacology test
A kind of A ring has the quinoid chalcone compounds of isopentene group to the anti-inflammatory effect for inhibiting NO release screening
Screening model is discharged with the NO that Turnover of Mouse Peritoneal Macrophages establishes lipopolysaccharides (LPS) induction, by measuring NO2-
Standard curve calculates NO burst size to screen the anti-inflammatory effect of test drug.Experiment is divided into blank control group (cell liquid is only added),
LPS group, administration group (LPS+ final concentration of 10-5The test drug of mol/L), positive control drug group (LPS+ final concentration of 10-6mol/L
Dexamethasone).Take 100 μ l of each group supernatant and equivalent Griess reagent (the 1% sulfanilamide (SN) solution containing 2.5% phosphoric acid with
0.1% naphthodiamide solution face used time 1:1 mixing) with mixed on micro oscillator, and be placed at room temperature standing 10 minutes.
570nm optical filter microplate reader measurement reading, according to NO2 -Standard curve calculates NO content to screen the anti-inflammatory effect of test drug.
The results are shown in Table 1, there are a kind of A ring the quinoid chalcone compounds of isopentene group to have apparent anti-inflammatory effect,
Concentration is 1 × 10-5When mol/L, it is 89.4~99.3% that NO, which generates inhibiting rate,.
1 one kind A ring of table has the quinoid chalcone compounds of isopentene group to the anti-inflammatory effect of the LPS NO release induced
Claims (12)
1. the quinoid chalcone compounds that one kind A ring has isopentene group, which is characterized in that have and tied shown in general formula (I)
Structure:
Wherein, R is 1,2,3,4 arbitrary substituent groups on phenyl ring,
The position of one substituent group are as follows:
The position of two substituent groups are as follows:
The position of three substituent groups are as follows:
The position of four substituent groups are as follows:
R is selected from: hydrogen, hydroxyl, methoxyl group, chlorine, bromine.
2. compound according to claim 1, which is characterized in that the compound is selected from following compound:
3. the preparation method of any compound of claim 1-2, which comprises the following steps:
(1) synthesis of 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
2,4,6- trihydroxy-acetophenones are taken to be added in aqueous alkali, ice-water bath stirring and dissolving takes 1.5-2.2 times of 2,4,6- trihydroxies
The bromo iso-amylene alkane of acetophenone mole, is added in aqueous solution, after sixty minutes, adjusts PH to 3 with dilute hydrochloric acid, then uses acetic acid
The washing of its organic phase, drying are finally used petrol ether/ethyl acetate mixed solvent by ethyl ester extraction, and silica gel column chromatography obtains yellow
Grease 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone；
(2) synthesis of 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone
It takes 3,5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone to be added in anhydrous propanone, stirs
After dissolution, 6-8 times 3 is taken, the carbonic acid of 5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone mole
Potassium after stirring 15 minutes, then takes 2-3 times 3, and 5- dihydroxy -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone rubs
You are added dropwise in acetone soln the chloromethyl methyl ether of amount, and after stirring 4-6 hours, filtering is dry by its filtrate, finally use petroleum
Ether/ethyl acetate mixed solvent, silica gel column chromatography obtain yellow oil 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6-
Diisoamyl alkenyl hexamethylene -2,4- dienone；
(3) methoxy methoxy base protection a kind of A ring have isopentene group quinoid chalcone compounds synthesis according to mole
Than 1:1~1:2, by 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6- diisoamyl alkenyl hexamethylene -2,4- dienone and replace
Benzaldehyde mixing is added ethanol water dissolution, adds 1-2.5 times of 3- hydroxy-5-methyl oxygen methoxyl group -2- acetyl group -6,6-
The basic catalyst of diisoamyl alkenyl hexamethylene -2,4- dienone mole after normal-temperature reaction 3 days, adjusts PH to 3 with dilute hydrochloric acid,
Then it is extracted with ethyl acetate, by the washing of its organic phase, drying, finally uses methanol/water mixed solvent, YMC Rp-C18Column chromatography
A kind of A ring for obtaining the protection of methoxy methoxy base has the quinoid chalcone compounds of isopentene group；
(4) one kind A ring has the synthesis of the quinoid chalcone compounds of isopentene group
There are a kind of A ring for taking methoxy methoxy base to protect the quinoid chalcone compounds of isopentene group tetrahydrofuran dissolution is added
Afterwards, dilute hydrochloric acid is added, heating reaction 10 hours after reactant is cooled to room temperature, is poured into water, then uses ethyl acetate
The washing of its organic phase, drying are finally used methanol/water mixed solvent, YMC Rp-C by extraction18Column, which chromatographs to obtain a kind of A ring, to be had
The quinoid chalcone compounds of isopentene group；
Wherein any one of the definition of R and claim 1-2 are identical.
4. preparation method according to claim 3, it is characterised in that: alkali described in step (1) is selected from sodium hydroxide or hydrogen
Potassium oxide；The volume ratio of petrol ether/ethyl acetate in the mixed solvent described in step (1), petroleum ether and ethyl acetate is 10:1.
5. preparation method according to claim 3, it is characterised in that: the mixing of petrol ether/ethyl acetate described in step (2)
In solvent, the volume ratio of petroleum ether and ethyl acetate is 20:1.
6. preparation method according to claim 3, it is characterised in that: the volume of ethyl alcohol and aqueous solution described in step (3)
Than for 3:2；Basic catalyst is selected from sodium hydroxide or potassium hydroxide；Methanol/water in the mixed solvent described in step (3), methanol
Volume ratio with water is 7:3.
7. preparation method according to claim 3, it is characterised in that: dilute hydrochloric acid concentration described in step (4) is 1-2mol/
L, the volume ratio with tetrahydrofuran are 1:1；Heating temperature described in step (4) is 30-50 DEG C；Methanol/water described in step (4)
The volume ratio of in the mixed solvent, methanol and water is 6:4.
8. a kind of pharmaceutical composition, it is characterised in that: contain the compound and medicine any in effective dose claim 1-2
Acceptable carrier on.
9. pharmaceutical composition according to claim 8, which is characterized in that the dosage form of the composition is selected from tablet, capsule, ball
Agent, granule, oral solution and suspension.
10. any compound of claim 1-2 is applied in the product of preparation treatment and/or prevention of inflammation.
11. application according to claim 10, which is characterized in that the inflammation is selected from vasculitis, osteoarthritis, neuritis
Disease.
12. application according to claim 10, which is characterized in that the product is selected from drug, health care product.
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