CN103992290A - Diarylethene structure similar compounds as well as preparation method and application thereof - Google Patents

Diarylethene structure similar compounds as well as preparation method and application thereof Download PDF

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CN103992290A
CN103992290A CN201410203747.7A CN201410203747A CN103992290A CN 103992290 A CN103992290 A CN 103992290A CN 201410203747 A CN201410203747 A CN 201410203747A CN 103992290 A CN103992290 A CN 103992290A
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methyl
methoxyl group
vinyl
compound
hydroxyl
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CN103992290B (en
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李卓荣
郑光辉
彭宗根
李玉环
岑山
季兴跃
金洁
李健蕊
孙文芳
马玲
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Institute of Medicinal Biotechnology of CAMS
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Abstract

The invention discloses a group of diarylethene structure similar compounds as well as a preparation method and application thereof. The provided compounds have a structure of a general formula I. Moreover, the invention further provides medicinal compositions containing the compounds serving as active ingredients. Researches discover that the compounds have pharmacological activities of resisting influenza viruses, Coxsackie B3 viruses, AIDS viruses, hepatitis B viruses, hepatitis C viruses and the like. Therefore, the invention further provides the application of the compounds and the medicinal compositions containing the compounds serving as active ingredients in preparation of anti-virus medicaments. The invention lays a foundation for deeply researching and developing the application of the compounds as clinical medicaments. The general formula I is as shown in the specification.

Description

Diarylethene structurally similar compounds and its preparation method and application
Technical field
The present invention relates to one group of diarylethene structurally similar compounds and preparation method thereof, also relate to the application of described compound in the medicines such as resisiting influenza virus infection, cells of coxsackie B 3 virus, hiv virus, hepatitis B virus, hepatitis C virus.And contain pharmaceutical composition and the application thereof of this compounds as active ingredient.The invention still further relates to the chemical total synthesis method of natural product cajanin analogue.
Background technology
Pigeonpea (Cajanus cajan L.Millsp.) is pulse family pigeonpea platymiscium, is the sixth-largest Food Legume in the world, is also unique woody Food Legume.Mainly be distributed in the ground such as South East Asia, India, Burma and Yunnan Province of China, Sichuan, Jiangsu, Guangdong, Guangxi, Taiwan and Hainan.Wood bean has pharmaceutical use widely, the main effect of its seed has that treatment liver renal edema, blood drench, blood etc. under hemorrhoid, and the effects such as that root has is clearing heat and detoxicating, dampness removing hemostasis, pain relieving, desinsection can treat that blood under swelling and pain in the throat, hemorrhoid, blood trickle are swollen, dysuria etc.Leaf of Cajan is mainly used in treatment burn infection, wound, sore, jaundice, pain relieving and desinsection etc. clinically.Leaf of Cajan exploitation is become to the medicine for the treatment of ischemic necrosis of the femoral head, safe and effective in clinical treatment necrosis of femoral head.Wood bean chemical characteristic and pharmacotoxicological effect result of study prove, the isopentene substituted diaryl ethene framework structured compound containing in Leaf of Cajan is mainly cajanin, Longistylin A and Longistylin C.The bioactivity research bibliographical information of domestic water/alcohol extracts about Leaf of Cajan is more, and Leaf of Cajan extract has the multiple biological activitys such as the sick disease of antimetabolic, anti-cerebral ischemia anoxia-induced apoptosis, anti-inflammatory analgesic.
The activity of the osteoporosis of cajanin monomer and runic thing is confirmed, experimental result is found in 0.01～100mg/L mass concentration, Leaf of Cajan aqueous extract can suppress the formation (P<0.05) of osteoclast like cell dose-dependently, also obviously suppresses the bone resorption activity (P<0.05) of osteoclast like cell simultaneously.
Luo Qingfeng etc. have also studied the treatment hyperlipidaemia effect of cajanin class formation analogue, result shows that Leaf of Cajan extract can obviously reduce serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) level of abnormal rising in Mice Body, and in effective dosage ranges without obvious toxic side effect.The anti-inflammatory of pigeonpea crude extract and analgesic activity also obtain the proof of experiment (referring to herbal medicine such as Sun Shaomei, 1995,26 (3:147-148), experimental result is found, laboratory sample cajanin preparation has obvious anti-inflammatory action, effect is better than Whitfield's ointment, and anti-inflammatory action presents dose-dependence.Cajanin preparation is to the effect of vascular permeability remarkable reduction compared with control group, and inhibiting rate is 38.96%.In addition, by cajanin preparation, the impact research of the mouse threshold of pain is found, gavaged the high low dose group of cajanin preparation (200,120mg/kg), all can extend the mouse threshold of pain, compared with before administration, extend and exceed one times, illustrate that cajanin preparation has obvious analgesic activity.
The demonstration of natural product pharmacological research result, cajanin and Leaf of Cajan stilbene class extract have pharmacological action widely, and multiple mankind's major disease is had to stronger pharmacologically active (as osteoporosis, hyperglycemia, hyperlipidemia, inflammation, tumour).Especially it has the mechanism of action (promoting bone growing suppresses bone resorption simultaneously) of the adjusting bone metabolism balance similar to oestrogenic hormon, and toxic side effect is little, has at home more deep research.
But, being still confined at present both at home and abroad the Natural Medicine Chemistry aspect such as extraction, separation and Structural Identification of natural product about the chemical research of pigeonpea stilbene class material, the quantity of the analogue with clear and definite structure obtaining is very limited.And, being subject to the restriction of medicament sources, the further investigation of natural product cajanin pharmacological action is difficult to launch.In the Chinese invention patent that the present inventor is 201110439374.X at application number, designed a series of cajanin compounds and carried out complete synthesis, for the diversity of further expanding such molecular structure of compounds provides chemical means and basis.
Summary of the invention
First passage chemical means of the present invention, further expands the diversity of cajanin compounds molecular structure, synthetic, optimize Structures of Natural Products; Synthesize first the novel cpd in a large number with diarylethene structural framework, and the synthetic cajanin analog derivative obtaining has been carried out to pharmacological action screening active ingredients, probed into the structure activity relationship that discloses this compounds; Research finds that this compounds has strong antiviral activity (as anti-HIV, HBV, HCV, influenza and Cox etc.) widely.For the realization that is optimized to medicine from activated natural product is laid a good foundation.
The present invention has also completed the transformation to Longistylin A ring first; Meanwhile, on the basis of the patent application that is 201110439374.X at application number, this compounds has been proposed again to another brand-new complete synthesis route.
In order to achieve the above object, the present invention adopts following technical scheme:
The invention provides the cajanin structurally similar compounds or its pharmaceutical salts that have as shown in general formula I,
R in formula 1represent H, replace or unsubstituted aryl, replace or unsubstituted heteroaryl, replace or unsubstituted alkyl, replacement or not substituted arene base, replace or unsubstituted alkoxyl formyl or carboxyl.Preferably, be selected from the phenyl of replacement, benzyl, styroyl, styryl.
R 2represent H, hydroxyl, replaces or unsubstituted alkoxyl group, replaces or unsubstituted methanoyl, replace or unsubstituted amino or halogen, or isoureido.
R 3represent H, isopentene group, isopentyl, 3 ', 7 '-dimethyl-octa-2 ', 6 '-dialkylene, replaces or unsubstituted aryl, allyl group, halogen, replaces or unsubstituted amino.
R 4represent H, hydroxyl, replaces or unsubstituted alkoxyl group, replaces or unsubstituted methanoyl, replace or unsubstituted amino or halogen, or isoureido.
R 5represent H, replace or unsubstituted aryl, replace or unsubstituted heteroaryl, replace or unsubstituted alkyl, replacement or not substituted arene base, replace or unsubstituted alkoxyl formyl or carboxyl;
R 6represent H, replace or unsubstituted aryl, replace or unsubstituted heteroaryl, replace or unsubstituted alkyl, replacement or not substituted arene base, replace or unsubstituted alkoxyl formyl or carboxyl;
In the present invention, preferred,
R 1be selected from hydrogen, carboxyl, methoxycarbonyl;
R 2be selected from hydroxyl, methoxyl group;
R 3be selected from isopentene group, isopentyl, isopentene group amine, isoamylamine;
R 5be selected from 2-furans, 2-thiazole, 2-imidazoles, 4-biphenyl, 2-pyridine, 3-pyridine, 4-pyridine, 6-methoxyl group-2-pyridine, 2,4-dihydroxy-benzene, 3,4-dihydroxy-benzene;
R 6be selected from 2-pyrroles, 3-pyrroles, 2-methoxyl group-3-pyrroles, 2-furans, 3-furans, 2-methoxyl group-3-furans, 2-thiazole, 5-thiazole, 4-methoxyl group-5-thiazole, 2-imidazoles, 3-imidazoles, 2-oxazole, 2-methoxyl group-5-oxazole, 5-methoxyl group-3H-imidazoles, 4-biphenyl, 2-pyridine, 3-pyridine, 4-pyridine, 6-methoxyl group-2-pyridine, 2,4-dihydroxy-benzene, 3,4-dihydroxy-benzene;
R 7be selected from isopentene group, isopentyl.
More than said in definition:
" replacement " can be but be not limited to be by halogen, alkoxyl group, and hydroxyl, alkyl, amino, alkylamino replaces.For example " substituted aryl " can be but be not limited to: by halogen, and alkoxyl group, hydroxyl, alkyl, amino and substituted-amino etc. is replaced in the phenyl of various positions.
" hetero-aromatic ring " can be but be not limited to be pyridine ring, thiazole ring, furan nucleus etc.
" alkyl " can be but be not limited to be the alkyl or cycloalkyl of carbonatoms at the straight or branched of 1-18, for example, methyl, ethyl, sec.-propyl, n-propyl, normal-butyl, isobutyl-, sec-butyl, the tertiary butyl, n-pentyl, isopentyl, n-hexyl, isohexyl etc. or its corresponding cycloalkyl.The more preferably low alkyl group of C1-C6.
" alkoxyl group " can be but be not limited to be the alkoxyl group of carbonatoms at 1-18, for example, methoxyl group, oxyethyl group, isopropoxy, positive propoxy, n-butoxy, isobutoxy, sec-butoxy, tert.-butoxy, n-pentyloxy, isopentyloxy, positive hexyloxy, different hexyloxy etc.More preferably C 1-C 6lower alkoxy.
" acyl group " can be but be not limited to be hydrocarbon substituted acyl or the aryl-acyl with 1-18 carbon, such as formyl radical, ethanoyl, sec.-propyl acyl group, n-propyl acyl group, allyl group acyl group, cyclopropyl acyl group, normal-butyl acyl group, isobutyl-acyl group, sec-butyl acyl group, tertiary butyl acyl group, n-pentyl acyl group, isopentyl acyl group, n-hexyl acyl group, isohexyl acyl group, phenyl acyl group, tolyl acyl group etc.
" alkoxyl formyl " or " ester group " can be but be not limited to be hydrocarbon ester appended (alkyl acyloxy) or the aryl ester group with 1-18 carbon, such as methanoyl, acetoxyl group, sec.-propyl acyloxy, n-propyl acyloxy, allyl group acyloxy, cyclopropyl acyloxy, normal-butyl acyloxy, isobutyl-acyloxy, sec-butyl acyloxy, tertiary butyl acyloxy, n-pentyl acyloxy, isopentyl acyloxy, n-hexyl acyloxy, isohexyl acyloxy, phenyl acyloxy, tolyl acyloxy etc.
" aminoacyl " or " carbamyl " can be to have the hydrocarbon of 1-18 carbon monosubstituted or disubstituted aminoacyl or aryl aminoacyl, such as N-methyl aminoacyl, ethyl aminoacyl, sec.-propyl aminoacyl, n-propyl aminoacyl, allyl group aminoacyl, cyclopropyl aminoacyl, normal-butyl aminoacyl, isobutyl-aminoacyl, sec-butyl aminoacyl, tertiary butyl aminoacyl, n-pentyl aminoacyl, isopentyl aminoacyl, n-hexyl aminoacyl, isohexyl aminoacyl, phenylamino acyl group, tolyl aminoacyl etc.
" halo " or " halogen " can be fluorine, chlorine, bromine or iodine.
The present invention also provides the synthetic method of the cajanin structurally similar compounds as shown in general formula I, specific as follows.
The invention provides the synthetic method of compound as shown in general formula I:
Work as R 1for carboxyl or hydrogen, R 2for hydroxyl, R 3for halohydrocarbon, R 4for alkoxyl group, R 5for H, X by all the other groups of C when general formula is defined above its synthetic method as route 1:
Route 1: the condensation under alkaline condition of acetylacetic ester and dicthenone obtains compound 2, compound 2 under alkaline condition in dipolar aprotic solvent alkylation generate compound 3, in non-polar solvent, there is free radical halogenating reaction and generate compound 4 in compound 3, compound 4 obtains compound 5 with tricresyl phosphite ester condensation, compound 5 obtains compound 6 with ketone or aldehyde reaction, compound 6 takes off alkyl again and obtains compound 7 under de-alkyl reagent exists, compound 7 obtains compound 8 with halohydrocarbon generation condensation reaction, compound 8 hydrolysis obtain compound of Formula I 9, compound 9 obtains compound of Formula I 10 by decarboxylic reaction under alkaline condition, wherein R 8, R 9, R 10for replacement or the unsubstituted alkyl of 1-18 carbon, R 3, R 6identical with the definition in aforementioned each general formula,
Route 2:
Route 2: the condensation under alkaline condition of acetylacetic ester and dicthenone obtains compound 2, compound 2 under alkaline condition in dipolar aprotic solvent alkylation generate compound 3, in non-polar solvent, there is free radical halogenating reaction and generate compound 4 in compound 3, compound 4 obtains compound 5 with tricresyl phosphite ester condensation, compound 5 obtains compound 6 with ketone or aldehyde reaction, compound 6 carries out dehydrogenation reaction and generates compound 11 under catalyst action, compound 11 generates compound 12 under the catalysis of Lin Dela palladium, compound 12 de-alkyl under de-alkyl reagent exists obtains compound 13, compound 13 obtains compound 14 with halohydrocarbon generation condensation reaction, compound 14 hydrolysis obtain compound of Formula I 15, compound 15 obtains compound of Formula I 16 by decarboxylic reaction under alkaline condition.
While preparing compound 4, said halide reagent can be but be not limited to be SO 2cl 2, NCS (being N-chlorosuccinimide), NBS (being N-bromosuccinimide), Br 2deng halide reagent, said solvent can be but be not limited to be CH 2cl 2, CHCl 3, CCl 4deng halogenated hydrocarbon solvent, or MeOH, EtOH, AcOH, propyl alcohol, Virahol, propyl carbinol, trimethyl carbinol isopolarity protonic solvent, or acetonitrile, DMF isopolarity aprotic solvent;
While preparing compound 11, said reagent can be but be not limited to be F 2, Cl 2, Br 2, I 2, said alkali can be but be not limited to be KOH, NaOH, K 2cO 3, Na 2cO 3deng mineral alkali, said solvent can be but be not limited to be CH 2cl 2, CHCl 3, CCl 4deng halogenated hydrocarbon solvent, or MeOH, EtOH, AcOH, propyl alcohol, Virahol, propyl carbinol, trimethyl carbinol isopolarity protonic solvent, or acetonitrile, DMF isopolarity aprotic solvent.
While preparing compound 12, said catalyzer can be but be not limited to be palladium, tetra-triphenylphosphine palladium, Pd/C, Pd/BaSO 4, the solvent of saying can be but be not limited to be CH 2cl 2, CHCl 3, CCl 4deng halogenated hydrocarbon solvent, or acetonitrile, DMF isopolarity aprotic solvent.
Again, the present invention also provides the preparation method of general formula I cajanin analogue, as shown in Scheme 3:
Route three:
1, 3-propanedioic acid and 2, 4, under the condition that 6-Trichlorophenol exists in phosphorus oxychloride, be condensed into compound 17, compound 17 and 2-amino-butenate reacting generating compound 18 in polar aprotic solvent, compound 18 alkylation under alkaline condition generates compound 19, in non-polar solvent, there is free radical halogenating reaction and generate compound 20 in compound 19, compound 20 is reacting generating compound 21 in phosphorous acid ester, compound 21 obtains compound 22 with ketone or aldehyde reaction, compound 22 takes off alkyl again and obtains compound 23 under de-alkyl reagent exists, compound 23 obtains compound 24 with halohydrocarbon generation condensation reaction, compound 24 hydrolysis obtain compound of Formula I 25, compound 25 obtains compound of Formula I 26 by decarboxylic reaction under alkaline condition, wherein R 8, R 9for replacement or the unsubstituted alkyl of 1-18 carbon, R 3, R 6, R 8, R 9identical with the definition in aforementioned each general formula.Said alkali can be but be not limited to be KOH, NaOH, K 2cO 3, Na 2cO 3deng mineral alkali, said acid can be but be not limited to be HCl, H 2sO 4, H 3pO 4deng mineral acid, X is Cl, Br, and I, solvent can be but be not limited to be water, various alcohol isopolarity protonic solvents or DMSO, DMF isopolarity aprotic solvent;
While preparing compound 17, said condensing agent can be but be not limited to be POCl 3, DIC, DCC; Or HCl, H 2sO 4, BF 3various mineral acids or the Lewis acid such as diethyl ether solution, said solvent can be but be not limited to be CH 2cl 2, CHCl 3, CCl 4deng halogenated hydrocarbon solvent, or MeOH, EtOH, AcOH, propyl alcohol, Virahol, propyl carbinol, trimethyl carbinol isopolarity protonic solvent, or acetonitrile, DMF isopolarity aprotic solvent.
While preparing compound 18, said solvent can be but be not limited to be PhBr, acetonitrile, DMF isopolarity aprotic solvent.
While preparing compound 19, said alkaline condition can be but be not limited to be KOH, NaOH, K 2cO 3, Na 2cO 3deng mineral alkali, said alkylating reagent can be but be not limited to be alkyl chloride, bromoalkane, idoalkane, and said solvent can be but be not limited to be acetonitrile, DMF isopolarity aprotic solvent.
Again, the present invention also provides the preparation method of general formula I class cajanin, as shown in Scheme 4:
Route 4:
1, 3-propanedioic acid and 2, 4, under the condition that 6-Trichlorophenol exists at catalyzer, be condensed into compound 17, compound 17 and 2-amino-butenate reacting generating compound 18 in polar aprotic solvent, compound 18 alkylation under alkaline condition generates compound 19, in non-polar solvent, there is free radical halogenating reaction and generate compound 20 in compound 19, compound 20 is reacting generating compound 21 in phosphorous acid ester, compound 21 obtains compound 22 with aldehyde reaction, compound 22 carries out dehydrogenation reaction and generates compound 22 ' under catalyst action, compound 22 ' generates compound 27 under the catalysis of Lin Dela palladium, compound 27 de-alkyl under de-alkyl reagent exists obtains compound 28, compound 28 obtains 29 with halohydrocarbon generation condensation reaction, compound 29 hydrolysis obtain general formula I V compound 30, compound 30 obtains compound of Formula I 31 by decarboxylic reaction under alkaline condition.Wherein R 8, R 9, R 10for replacement or the unsubstituted alkyl of 1-18 carbon, R 3, R 5identical with the definition in aforementioned each general formula.Said alkali can be but be not limited to be KOH, NaOH, K 2cO 3, Na 2cO 3deng mineral alkali, said acid can be but be not limited to be HCl, H 2sO 4, H 3pO 4deng mineral acid, X is Cl, Br, and I, solvent can be but be not limited to be water, various alcohol isopolarity protonic solvents or DMSO, DMF isopolarity aprotic solvent;
Again, as R in general formula I 3transformation, when complementary basis group defines as aforementioned formula, its synthetic method as shown in Scheme 5:
Route 5:
The condensation under alkaline condition of acetylacetic ester and crotonate obtains compound 32, compound 32 bromination aromatic rings obtain compound 33, compound 33 alkylations obtain compound 34, compound 34 obtains compound 35 with halide reagent generation free radical halogenating reaction, compound 35 obtains compound 36 with the condensation of organic phosphine reagent, there is substitution reaction and obtain alkylate 37 in compound 36, compound 37 obtains compound 38 with aldehydes or ketones condensation under alkaline condition, there is dealkylation and obtain 39 in compound 38, compound 39 obtains preparing the compound 40 in claim 1 with structure shown in general formula (I) through hydrolysis reaction.
Invention effect:
According to the above route and method, the present invention has synthesized the similar thing of a large amount of novel diarylethenes first, and the chemistry that has completed first pyridine replacement cajanin is complete synthesis, and trans cajanin has been proposed again to another brand-new complete synthesis route.The present invention also measures the anti-resisiting influenza virus infection of the cajanin derivative of synthesized, cells of coxsackie B 3 virus, hiv virus, hepatitis B virus, hepatitis C virus isoreactivity first, and the activity of part of compounds exceedes primer cajanin.The structure of invention compound and determination of pharmacological activity result are respectively in table 1, table 2, table 3.
Adopt cell culture method to find the antiviral activity screening of invention compound, this compounds has stronger preventing respiratory viruses effect (shown in table 1).Wherein, the compound anti-influenza virus activities such as compound 8n, 9f, 9g, 10c, 10e, 24d, 24e, 16a, 25b and 31e are obviously better than primer cajanin, and compared with clinical medicine Tamiflu, the antiviral activity of foregoing invention compound and Tamiflu are quite even stronger.
Table 1: the structure of invention compound and antiviral activity
NA represents there is no activity.
The invention still further relates to described compound at anti-COX-B3, the application of HIV virus aspect, it the results are shown in Table 2, wherein, compound 8d, 8g, 8k, 10b, 15b, 15h, 16h, 24i, 25i, 40e, 40d etc. have shown stronger anti-COX-B3, the activity of HIV virus.
Table 2: the structure of invention compound and antiviral activity
The invention still further relates to described compound and suppressing HBV, the application of HCV virus aspect, it the results are shown in Table 3, wherein, the compounds such as compound 9n, 9o, 10g, 10l, 10m, 10o, 10t, 14g, 14h, 15b, 15c, 15f, 15g, 39c have shown stronger anti-HBV, the activity of HCV virus.
Table 3: the structure of invention compound and antiviral activity
NA is not for there is no activity
The invention still further relates to neuroprotective, the function of resisting osteoporosis of described compound.Bibliographical information, pigeonpea stilbene compound belongs to phytoestrogen, and to have estrogen-like effects relevant with it for the function of resisting osteoporosis of natural product.The present invention is studied confirmation to the cajanin sterling obtaining by chemical means to osteoporosis in ovariectomized rats protection effect, result demonstration, and its osteoporosis effect is in animal body better than clinical medicine Evista.
In addition, described in background of invention, that pigeonpea stilbene class extract and cajanin, Longistylin A, Longistylin C have is antitumor, reducing blood sugar and blood fat, anti-inflammatory and analgesic effect are widely studied and report.The compounds of this invention is the analog taking natural product cajanin, Longistylin A as lead compound, and the compounds of this invention has primer simultaneously, and similarly antitumor, reducing blood sugar and blood fat, anti-inflammatory and analgesic effect are apparent.Therefore, the invention still further relates to the application of described compound at aspects such as antitumor, reducing blood sugar and blood fat, relieving inflammation and relaxing pain.
And; the present invention also provides a kind of pharmaceutical composition for antiviral and bacterium infection, neuroprotective, antimetabolic disease (as osteoporosis, hyperlipidemia, hyperglycemia) etc.; described in comprising in this pharmaceutical composition, there is the compound or pharmaceutically acceptable salt thereof of general formula I, also can further comprise one or more pharmaceutically acceptable pharmaceutical adjuvants.
Wherein, described in there is general formula I compound or pharmaceutically acceptable salt thereof as activeconstituents, the weight content in this pharmaceutical composition is 0.1%-99.5%.Preferably, in this pharmaceutical composition, contain the activeconstituents that weight ratio is 0.5%-99.5%.
Further, the invention provides described composition in the application of preparing in the medicines such as antibacterium and virus infection, neuroprotective, antimetabolic disease (as osteoporosis, hyperlipidemia, hyperglycemia).
Embodiment
Further describe the present invention below in conjunction with specific embodiment, advantage and disadvantage of the present invention will be more clear along with description.But these embodiment are only exemplary, scope of the present invention are not formed to any restriction.It will be understood by those skilled in the art that lower without departing from the spirit and scope of the present invention and can the details of technical solution of the present invention and form be modified or be replaced, but these amendments and replacement all fall within the scope of protection of the present invention.
Embodiment 1
The preparation (2) of 2,4-dihydroxyl-6-methyl-toluate
Methyl acetoacetate (50g, 0.43mol) be dissolved in 300ml ether, add NaH (15.50g0.45mol in room temperature, 70%), finish, drip dicthenone (37g in this temperature, diethyl ether solution 0.45mol), finish, at room temperature reaction 3-4h, now reaction system becomes yellow dirty solution.Termination reaction, is added to reaction solution in 500ml frozen water mixed solution, separates ether layer, water layer 50ml extracted with diethyl ether 2 times, and combined ether layer, and wash with saturated common salt, anhydrous magnesium sulfate drying spends the night.Filter, revolve to steam and remove ether, residuum sherwood oil: ethyl acetate=8:1 crosses silicagel column, obtains 35g (45%) white solid and is target product. 1H-NMR(400M,DMSO-d 6)δ(ppm):10.66(s,1H),9.95(s,1H),6.16(d,J＝2.4Hz,1H),6.14(d,J＝2.4Hz,1H),3.78(s,3H),2.26(s,3H)
Embodiment 2
The preparation (3) of 2,4-dimethoxy-6-methyl-toluate
Compound 2 (12g, 0.066mol) is dissolved in 50ml acetone, adds salt of wormwood (27.3g, 0.198mol), methyl iodide (28g, 0.198mol), heating reflux reaction 3h, stopped reaction, reaction solution adds in 100ml water, is extracted with ethyl acetate (350ml), merge organic layer, organic layer is used 10% sodium hydroxide solution successively, 10% hydrochloric acid, saturated common salt washing.Organic layer anhydrous magnesium sulfate drying.Filter, revolve and steam except desolventizing, obtain colorless oil, obtain clear crystal 13.5g (97%) with petrol ether/ethyl acetate recrystallization. 1H-NMR(400M,CDCl 3)δ(ppm):6.31(s,2H),3.88(s,3H),3.80(s,6H),2.28(s,3H)
Embodiment 3
2-brooethyl-4,6-dimethoxy p-methyl (4)
Compound 3 (10g, 0.0476mol) is dissolved in 50ml tetracol phenixin, nitrogen protection; reflux adds NBS (8.5g, 0.0476mol)+BPO (0.11g in batches; mixture 0.476mmol), adds, back flow reaction 1h.Stopped reaction, cooling, to filter, filtrate is spin-dried for, and obtains light yellow solid, obtains white solid 11.3g (82%) with dehydrated alcohol recrystallization. 1H-NMR(400M,CDCl 3)δ(ppm):6.74(s,1H),6.47(s,1H),4.66(s,2H),3.96(s,3H),3.93(s,3H),3.85(s,3H).
Embodiment 4
2-diethyl phosphite methyl-4,6-dimethoxy p-methyl (5)
The mixture of compound 4 (12g, 0.0326mol) and triethyl-phosphite (10.83g, 0.065mol), heating reflux reaction 2h.Stopped reaction, cooling, the triethyl-phosphite that pressure reducing and steaming is excessive, residuum methylene dichloride: methyl alcohol=40:1 crosses silicagel column and obtains white solid 12.8g (92%). 1H-NMR(400M,CDCl 3)δ(ppm):6.76(s,1H),6.43(s,1H),4.02(q,J＝6.4Hz,4H),3.92(s,3H),3.90(s,3H),3.80(s,3H),3.78(d,J＝22.8Hz,2H),1.26(t,J＝6.4Hz,6H).
Embodiment 5
(E)-2,4-dimethoxy-6-[styryl] methyl benzoate (6)
Compound 5 (10g, 0.0289mol) is dissolved in 100ml tetrahydrofuran (THF), adds NaH (1.09g, 0.0318mol), phenyl aldehyde (3.68g, 0.0347mol), heating reflux reaction 2h, stopped reaction, reaction solution joins in 200ml water, is extracted with ethyl acetate (3100ml), merges organic layer, organic layer is washed with saturated common salt, anhydrous magnesium sulfate drying.Filter, revolve to boil off and desolventize, residue oily matter obtains clear crystal 6.2g (72%) with petrol ether/ethyl acetate recrystallization. 1H-NMR(400M,CDCl 3)δ(ppm):7.47(d,J＝7.2Hz,2H),7.35(t,J＝7.2Hz,2H),7.29(m,1H),7.06(dd,J＝16Hz,2H),6.77(s,1H),6.42(s,1H),3.92(s,3H),3.88(s,3H),3.83(s,3H).
Embodiment 6
(E)-2-hydroxyl-4-methoxyl group-6-[styryl] methyl benzoate (7)
Compound 6 (6g, 0.0201mol) is dissolved in 50ml methylene dichloride, drips BBr in the time of 0 DEG C 3dichloromethane solution (24ml, 1M), drip off room temperature reaction 1h, stopped reaction.Reaction solution washes with water, anhydrous magnesium sulfate drying.Filter, revolve and steam except desolventizing, residuum is crossed silicagel column by petroleum ether/ethyl ether and is obtained white solid 5.4g (95%). 1H-NMR(400M,CDCl 3)δ(ppm):10.28(s,1H),7.52(d,J＝7.2Hz,2H),7.38(t,J＝7.2Hz,2H),7.28(t,J＝7.2Hz,1H),7.15(dd,J＝16Hz,2H),6.80(d,J＝2.4Hz,1H),6.40(d,J＝2.4Hz,1H),3.82(s,3H),3.79(s,3H).
Embodiment 7
(E)-2-hydroxyl-3-isopentene group-4-methoxyl group-6-[styryl] methyl benzoate (8)
Compound 7 (5g, 0.0176mol) be dissolved in 50ml ether, add sodium Metal 99.5 (0.43g, 0.0184mol), stirring at room temperature 4h, add isoprenyl bromide (3.2g, 0.0211mol), back flow reaction 4h, stopped reaction, reaction solution is water successively, and saturated common salt washing, separates organic layer.Organic layer anhydrous magnesium sulfate drying, filters, and revolves to boil off to desolventize to obtain yellow oil, crosses silicagel column and obtains white solid 3.8g (61%). 1H?NMR(400M,DMSO-d 6)δ(ppm):11.66(s,1H),7.84(d,J＝16.0Hz,1H),7.52(d,J＝7.2Hz,2H),7.38(t,J＝7.2Hz,2H),7.27(t,J＝7.2Hz,1H),7.00(d,J＝16.0Hz,1H),6.78(s,1H),5.12(t,J＝6.8Hz,1H),3.94(s,3H),3.91(s,3H),3.24(d,J＝6.8Hz,2H),1.71(s,3H),1.61(s,3H).
Embodiment 8
(E)-2-hydroxyl-3-isopentene group-4-methoxyl group-6-[styryl] phenylformic acid (1, cajanin)
Compound 8 (3g, 0.0085mol) is dissolved in the aqueous sodium hydroxide solution of 30ml20%, heating reflux reaction 2h, and stopped reaction, cooling.Adding 10% dilute hydrochloric acid to adjust pH to be less than 2. now has a large amount of white precipitates to generate, and filters, and the dry white solid that to obtain, obtains white solid 2.6g (90%) with petrol ether/ethyl acetate recrystallization. 1H?NMR(400M,CDCl 3)δ(ppm):11.58(s,1H),7.81(d,J＝16.0Hz,1H),7.52(d,J＝7.2Hz,2H),7.38(t,J＝7.2Hz,2H),7.28(t,J＝7.2Hz,1H),6.83(d,J＝16.0Hz,1H),6.65(s,1H),5.22(t,J＝6.8Hz,1H),3.95(s,3H),3.38(d,J＝6.8Hz,2H),1.79(s,3H),1.68(s,3H).
Embodiment 9
(E)-3-methoxyl group-2-(3-methyl but-2-ene base)-5-styryl-phenol (9)
Compound 8 (1g, 2.84mmol) is dissolved in 10ml ethanol and 5ml water, adds KOH (0.5g, 8.5mmol), microwave reaction 1h (30W, 25psi, 100 DEG C), and reaction is finished.Reaction solution adds in 50ml water, is less than 2 with 10% salt acid for adjusting pH, is extracted with ethyl acetate (3X30ml), merges organic layer, and organic layer is again with saturated common salt washing, and anhydrous magnesium sulfate drying spends the night.Filter next day, concentrates to obtain light yellow solid, then cross silicagel column by petrol ether/ethyl acetate, obtains white solid 0.66g (80%). 1H?NMR(400MHz,CDCl 3):7.50(d,J＝7.2Hz,2H),7.35(t,J＝7.2Hz,2H),7.28(t,J＝7.2Hz,1H),7.02(dd,J＝16.0Hz,2H),6.66(s,1H),6.64(s,1H),5.24(m,2H),3.87(s,3H),3.41(d,J＝6.8Hz,2H),1.82(s,3H),1.75(s,3H).
Embodiment 10
(E)-2,4-dimethoxy-6-(2-thiazol-2-yl vinyl) methyl benzoate (6a)
Taking 2-thiazole phenyl aldehyde as raw material, obtain this compound, white solid (83%) with the similar method of embodiment 5. 1H?NMR(500MHz,CDCl 3)δ7.74(s,1H),7.41(d,J＝18.5Hz,1H),7.30(d,J＝18.5Hz,2H),6.71(s,1H),6.66(s,1H),3.95(s,6H),3.81(s,3H).
Embodiment 11
(E)-2-hydroxyl-4-methoxyl group-6-(2-thiazol-2-yl-vinyl)-methyl benzoate (7a)
Taking compound 6a as raw material, obtain compound, white solid (95%) by the method reaction of embodiment 6.1HNMR(500MHz,CDCl3)δ7.75(s,1H),7.49(d,J＝10.5Hz,2H),7.42(m,1H),6.68(s,1H),6.53(s,1H),3.98(s,3H),3.89(s,3H).
Embodiment 12
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-methyl benzoate (8a);
Taking compound 7a as raw material, obtain compound 8a according to the method for embodiment 7, white solid (62%).1HNMR(500MHz,CDCl3)δ7.76(s,1H),7.57–7.17(m,4H),6.66(s,1H),5.41(s,1H),3.96(s,3H),3.85(s,3H),3.61(d,J＝6.5Hz,2H),1.92(s,3H),1.81(s,3H).
Embodiment 13
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-phenylformic acid (9a);
Taking compound 8a as raw material, obtain compound 9a according to the method for embodiment 8, white solid (90%).1H?NMR(500MHz,CDCl3)δ7.76(s,1H),7.50(d,J＝3.5Hz,2H),7.40(d,J＝13.5Hz,2H),6.76(s,1H),5.42(s,J＝6.5Hz,1H),3.82(s,3H),3.64(d,J＝6.5Hz,2H),1.91(s,3H),1.83(s,3H).
Embodiment 14
(E)-3-methoxyl group-2-(3-methyl but-2-ene base)-5-(2-thiazol-2-yl-vinyl)-phenol (10a);
Taking compound 9a as raw material, obtain compound 10a according to the method for embodiment 9, white solid (86%).1H?NMR(500MHz,CDCl3)δ7.75(s,1H),7.44(d,J＝3.5Hz,2H),7.35(s,1H),7.31(s,1H),6.40(d,J＝3.5Hz,2H),5.83(s,1H),5.48(d,J＝6.5Hz,1H),3.78(s,3H),3.59(d,J＝6.5Hz,2H),1.91(s,3H),1.83(s,3H).
Embodiment 15
(E)-2-[2-(1H-imidazoles-2-yl)-vinyl]-4,6-dimethoxy p-methyl (6b);
Taking 2-imidazoles phenyl aldehyde as raw material, obtain this compound, white solid (81%) with the similar method of embodiment 5.1H?NMR(500MHz,CDCl3)δ7.65(s,1H),7.23(d,J＝7.5Hz,2H),7.07(s,1H),6.69(s,1H),6.62(s,1H),6.50(s,1H),3.91(s,6H),3.89(s,3H).
Embodiment 16
(E)-2-hydroxyl-6-[2-(1H-imidazoles-2-yl)-vinyl]-4-methoxyl group-methyl benzoate (7b);
Taking compound 6b as raw material, obtain compound 7b, white solid (93%) by the method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ7.46(s,1H),7.16(d,J＝18.5Hz,2H),7.02(s,1H),6.66(s,1H),6.52(d,J＝12.7Hz,2H),3.96(s,3H),3.85(s,3H).
Embodiment 17
(E)-2-hydroxyl-6-[2-(1H-imidazoles-2-yl)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate (8b)
Taking compound 7b as raw material, obtain compound 8b according to the method for embodiment 7, white solid (54%).1HNMR(500MHz,CDCl3)δ7.65(s,1H),7.48(s,1H),7.22(d,J＝7.5Hz,2H),7.15(s,1H),7.11(d,J＝37.9Hz,2H),6.64(s,1H),6.50(s,1H),5.42(s,1H),3.96(s,3H),3.82(s,3H),3.60(s,2H),1.90(s,3H),1.82(s,3H).
Embodiment 18
(E)-2-hydroxyl-6-[2-(1H-imidazoles-2-yl)-vinyl]-4-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (9b)
Taking compound 8b as raw material, obtain compound 9b according to the method for embodiment 8, white solid (90%).1H?NMR(500MHz,CDCl3)δ7.50(s,1H),7.36(s,1H),7.09(s,1H),6.99(d,J＝4.8Hz,2H),6.78(s,1H),6.50(s,1H),5.44(s,1H),3.83(s,3H),3.61(s,2H),1.91(s,3H),1.83(s,3H).
Embodiment 19
(E)-5-[2-(1H-imidazoles-2-yl) vinyl]-3-methoxyl group-2-(3-methyl but-2-ene base)-phenol (10b)
Taking compound 9b as raw material, obtain compound 10b according to the method for embodiment 9, white solid (88%).1H?NMR(500MHz,CDCl3)δ7.52(s,1H),7.13(d,J＝7.5Hz,2H),6.92(d,J＝7.5Hz,1H),6.49(s,1H),6.40(d,J＝3.0Hz,2H),5.83(s,1H),5.47(s,1H),3.78(s,3H),3.59(s,2H),1.90(s,3H),1.81(s,3H).
Embodiment 20
(E)-2,4-dimethoxy-6-(2-oxazole-2-base vinyl) methyl benzoate (6c)
Taking 2-oxazole phenyl aldehyde as raw material, obtain compound 6c, white solid (92%) by the method reaction of embodiment 5.1H?NMR(500MHz,CDCl3)δ7.63(s,1H),7.16(d,J＝8.0Hz,1H),7.06(t,J＝8.0Hz,1H),6.73(s,1H),6.62(s,1H),3.96(d,J＝16.3Hz,6H),3.85(s,3H).
Embodiment 21
(E)-2-hydroxyl-4-methoxyl group-6-(2-oxazole-2-base vinyl) methyl benzoate (7c)
Taking compound 6c as raw material, obtain compound 7c according to the method for embodiment 6, white solid (96%).1HNMR(500MHz,CDCl3)δ7.67(s,1H),7.44(s,1H),7.20(s,1H),7.11(s,1H),6.68(s,1H),6.52(s,1H),3.99(s,3H),3.81(s,3H).
Embodiment 22
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-methyl benzoate (8c)
Taking compound 7c as raw material, obtain compound 8c according to the method for embodiment 7, white solid (70%).1H?NMR(500MHz,CDCl3)δ9.04(s,1H),7.65(s,1H),7.40(s,1H),7.22(d,J＝8.0Hz,1H),7.06(d,J＝8.0Hz,1H),6.66(s,1H),5.44(t,J＝7.5Hz,1H),3.95(s,3H),3.81(s,3H),3.60(d,J＝7.5Hz,2H),1.95(s,3H),1.82(s,3H).
Embodiment 23
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-phenylformic acid (9c)
Taking compound 8c as raw material, obtain compound 9c according to the method for embodiment 8, white solid (86%).1HNMR(500MHz,CDCl3)δ7.69(d,J＝16.0Hz,1H),7.50(s,1H),7.22(d,J＝16.0Hz,1H),6.92(s,1H),6.75(s,1H),5.41(t,J＝7.0Hz,1H),3.82(s,3H),3.64(d,J＝7.0Hz,2H),1.91(s,3H),1.83(s,3H).
Embodiment 24
(E)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-(2-oxazole-2-base vinyl)-phenol (10c)
Taking compound 9c as raw material, obtain compound 10c according to the method for embodiment 9, white solid (95%).1H?NMR(500MHz,CDCl3)δ7.67(s,1H),7.26(s,1H),7.20(s,1H),6.96(s,1H),6.40(d,J＝3.1Hz,2H),5.83(s,J＝7.0Hz,1H),5.48(s,1H),3.78(s,3H),3.58(d,J＝7.0Hz,2H),1.91(s,3H),1.83(s,3H).
Embodiment 25
(E)-2,4-dimethoxy-6-[2-(1H-pyrroles-2-yl)-vinyl] methyl benzoate (6d)
Taking 2-pyrroles's phenyl aldehyde as raw material, obtain compound 6d, white solid (87%) by the method reaction of embodiment 5.1H?NMR(500MHz,CDCl3)δ9.67(s,1H),7.10–6.98(m,3H),6.71(s,1H),6.60(s,1H),6.47(s,1H),6.09(s,1H),3.98(s,3H),3.97(s,3H),3.81(s,3H).
Embodiment 26
(E)-2-hydroxyl-4-methoxyl group-6-[2-(1H-pyrroles-2-yl)-vinyl] methyl benzoate (7d)
Taking compound 6d as raw material, obtain compound 7d according to the method for embodiment 6, white solid (96%).1HNMR(500MHz,CDCl3)δ9.75(s,1H),7.28(s,1H),7.07(d,J＝5.5Hz,2H),6.65(s,1H),6.50(d,J＝11.1Hz,2H),6.11(s,1H),3.97(s,3H),3.85(s,3H).
Embodiment 27
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-methyl benzoate (8d)
Taking compound 7d as raw material, obtain compound 8d according to the method for embodiment 7, white solid (52%).1H?NMR(500MHz,CDCl3)δ9.65(s,1H),9.04(s,1H),7.37–7.04(m,3H),6.67(s,1H),6.51(s,1H),6.12(s,1H),5.43(t,J＝7.5Hz,1H),3.98(s,3H),3.81(s,3H),3.51(d,J＝7.5Hz,2H),1.93(s,3H),1.80(s,3H).
Embodiment 28
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-phenylformic acid (9d)
Taking compound 8d as raw material, obtain compound 9d according to the method for embodiment 8, white solid (90%) 1HNMR (500MHz, CDCl3) δ 9.74 (s, 1H), 8.42 (s, 3H), 7.37 – 7.03 (m, 2H), 6.79 (s, 1H), 6.78 – 6.46 (m, 2H), 6.45 (s, 1H), 6.11 (s, 1H), 5.45 (s, 1H), 3.74 (s, 3H), 3.66 (s, 2H), 1.92 (s, 3H), 1.83 (s, 3H).
Embodiment 29
(E)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-[2-(1H-pyrroles-2-yl)-vinyl]-phenol (10d)
Taking compound 9d as raw material, obtain compound 10d according to the method for embodiment 9, white solid (89%).1H?NMR(500MHz,CDCl3)δ9.72(s,1H),7.07–6.72(m,3H),6.60(d,J＝4.5Hz,2H),6.45(s,1H),6.08(s,1H),5.84(s,1H),5.45(t,J＝7.5Hz,1H),3.80(s,3H),3.56(d,J＝7.5Hz,2H),,1.91(s,3H),1.82(s,3H).
Embodiment 30
(E)-2-(2-biphenyl-4-base-vinyl)-4,6-dimethoxy p-methyl (6e)
Taking 4-phenyl phenyl aldehyde as raw material, obtain this compound, white solid (84%) with the similar method of embodiment 5.1H?NMR(500MHz,CDCl3)δ7.81–7.68(m,2H),7.68(s,1H),7.70–7.55(m,2H),7.52–7.46(m,1H),7.42(s,1H),7.34(s,1H),6.84(s,1H),6.60(s,1H),3.99(s,6H),3.87(s,3H)
Embodiment 31
(E)-2-(2-biphenyl-4-base-vinyl)-6-hydroxyl-4-methoxyl group-methyl benzoate (7e)
Taking compound 6e as raw material, obtain compound 7e, white solid (92%) by the method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ7.83–7.70(m,2H),7.70–7.68(m,1H),7.68–7.60(m,2H),7.55–7.24(m,1H),7.41(s,1H),7.41(s,1H),7.16(s,1H),6.77(s,1H),6.50(s,1H),3.96(s,3H),3.81(s,3H).
Embodiment 32
(E)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (8e)
Taking compound 7e as raw material, obtain compound 8e according to the method for embodiment 7, white solid (55%).1HNMR(500MHz,CDCl3)δ7.73(dd,J＝18.5,14.0Hz,3H),7.71(d,J＝18.5Hz,1H),7.74–7.57(m,2H),7.55(s,1H),7.52–7.46(m,1H),7.42(s,1H),7.13(s,1H),7.03(s,1H),6.78(s,1H),5.43(s,1H),3.97(s,3H),3.83(s,3H),3.60(s,2H),1.91(s,3H),1.83(s,3H).
Embodiment 33
(E)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (9e)
Taking compound 8e as raw material, obtain compound 9e according to the method for embodiment 8, white solid (77%) 1HNMR (500MHz, CDCl3) δ 7.83 – 7.76 (m, 1H), 7.76 – 7.68 (m, 3H), 7.68 – 7.53 (m, 3H), 7.51 – 7.45 (m, 2H), 7.40 (s, 1H), 7.08 (d, J=17.5Hz, 2H), 6.78 (s, 1H), 5.41 (t, J=7.5Hz, 1H), 3.80 (s, 3H), 3.52 (d, J=7.5Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 34
(E)-5-(2-biphenyl-4-base-vinyl)-3-methoxyl group-2-(3-methyl but-2-ene base)-phenol (10e)
Taking compound 9e as raw material, obtain compound 10e according to the method for embodiment 9, white solid (91%).1H?NMR(500MHz,CDCl3)δ7.68–7.54(m,6H),7.54–7.37(m,3H),7.22(d,J＝7.0Hz,2H),6.58(d,J＝6.5Hz,2H),5.83(s,1H),5.56(s,1H),3.82(s,3H),3.52(s,2H),1.90(s,3H),1.82(s,3H).
Embodiment 35
(E)-2-(2-furans-2-base-vinyl)-4,6-dimethoxy p-methyl (6f)
Taking 2 furan carboxyaldehyde as raw material, obtain this compound, white solid (84%) with the similar method of embodiment 5.1H?NMR(500MHz,CDCl3)δ7.60(s,1H),7.12(t,J＝15.0Hz,1H),6.79(s,J＝15.0Hz,2H),6.71(s,1H),6.60(s,1H),6.42(s,1H),3.98(s,3H),3.94(s,3H),3.82(s,3H).
Embodiment 36
(E)-2-(2-furans-2-base-vinyl)-6-hydroxyl-4-methoxyl group-methyl benzoate (7f)
Taking compound 6f as raw material, obtain compound 7f, white solid (92%) by the method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ7.62(d,J＝22.5Hz,1H),7.39(d,J＝15.0Hz,1H),7.04(dd,J＝22.5,15.0Hz,2H),6.80(s,1H),6.65(s,1H),6.51(s,1H),6.44(s,1H),3.97(s,3H),3.81(s,3H).
Embodiment 37
(E)-6-(2-furans-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (8f)
Taking compound 7f as raw material, obtain compound 8f according to the method for embodiment 7, white solid (70%).1HNMR(500MHz,CDCl3)δ7.73(s,1H),7.60(s,1H),7.10(d,J＝10.5Hz,2H),6.79(s,1H),6.63(s,1H),6.43(s,1H),5.40(s,J＝7.5Hz,1H),3.99(s,3H),3.83(s,3H),3.55(s,J＝7.5Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 38
(E)-6-(2-furans-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (9f)
Taking compound 8f as raw material, obtain compound 9f according to the method for embodiment 8, white solid (88%) 1HNMR (500MHz, CDCl3) δ 7.82 (s, 1H), 7.62 (s, 1H), 7.50 (m, 1H), 7.01 (m, 1H), 6.77 (d, J=17.5Hz, 2H), 6.44 (s, 1H), 5.40 (s, J=6.5Hz, 1H), 3.83 (s, 3H), 3.58 (s, J=6.5Hz, 2H), 1.92 (s, 3H), 1.83 (s, 3H).
Embodiment 39
(E)-5-(2-furans-2-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol (10f)
Taking compound 9f as raw material, obtain compound 10f according to the method for embodiment 9, white solid (92%).1HNMR(500MHz,CDCl3)δ7.60(s,1H),7.12(s,1H),7.03(s,1H),6.84(s,1H),6.49(s,1H),6.44(d,J＝3.3Hz,2H),5.84(s,1H),5.39(t,J＝6.5Hz,1H),3.79(s,3H),3.51(d,J＝6.5Hz,2H),1.96(s,3H),1.80(s,3H).
Embodiment 40
(E)-2-[2-(3,4-dihydroxyl-phenyl)-vinyl]-4,6-dimethoxy p-methyl (6g)
For raw material, obtain this compound, white solid (88%) with the similar method of embodiment 5 with 3,4-Dihydroxy benzaldehyde.1H?NMR(500MHz,CDCl3)δ7.17(s,1H),7.12–6.61(m,4H),6.81(s,1H),6.81(s,1H),6.60(s,1H),5.78(s,1H),5.55(s,1H),3.96(s,6H),3.86(s,3H).
Embodiment 41
(E)-2-[2-(3,4-dihydroxyl-phenyl)-vinyl]-6-hydroxyl-4-methoxyl group-methyl benzoate (7g)
Taking compound 6g as raw material, obtain compound 7g, white solid (91%) by the method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ7.40(s,1H),7.23–6.96(m,3H),6.87(s,1H),6.75(s,1H),6.49(s,1H),5.49(s,1H),5.42(s,1H),3.93(s,3H),3.87(s,3H).
Embodiment 42
(E)-6-[2-(3,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (8g)
Taking compound 7g as raw material, obtain compound 8g according to the method for embodiment 7, white solid (71%).1HNMR(500MHz,CDCl3)δ9.15(s,1H),7.42(s,1H),7.21(s,1H),7.06(d,J＝1.7Hz,2H),6.85(s,1H),6.76(s,1H),5.62(s,1H),5.59(s,1H),5.57(t,J＝7.5Hz,1H),3.96(s,3H),3.83(s,3H),3.51(s,J＝7.5Hz,2H),1.91(s,3H),1.83(s,3H).
Embodiment 43
(E)-6-[2-(3,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (9g)
Taking compound 8g as raw material, obtain compound 9g according to the method for embodiment 8, white solid (93%) 1HNMR (500MHz, CDCl3) δ 9.04 (s, 1H), 7.45 – 7.11 (m, 2H), 7.07 (s, 2H), 6.85 (d, J=6.0Hz, 2H), 5.72 – 5.52 (m, 3H), 3.83 (s, 3H), 3.54 (s, J=6.5Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 44
(E)-4-{2-[3-hydroxy-5-methyl oxygen base-4-(3-methyl but-2-ene base)-phenyl]-vinyl }-benzene-1,2-glycol (10g)
Taking compound 9g as raw material, obtain compound 10g, white solid (93%) according to the similar method of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.12(s,1H),7.00(dt,J＝16.0,8.0Hz,1H),6.91(s,1H),6.91–6.72(m,3H),6.53(d,J＝11.5Hz,2H),5.82(s,1H),5.69(s,1H),5.54(t,J＝7.5Hz,1H),3.74(s,3),3.50(s,J＝7.5Hz,2H),1.90(s,3H),1.81(s,3H).
Embodiment 45
(E)-2-[2-(2,4-dihydroxyl-phenyl)-vinyl]-4,6-dimethoxy p-methyl (6h)
For raw material, obtain this compound, white solid (80%) with the similar method of embodiment 5 with 2,4-Dihydroxy benzaldehyde.1H?NMR(500MHz,CDCl3)δ7.62(s,1H),7.39(s,1H),7.04(s,1H),6.80(s,1H),6.65(s,1H),6.51(s,1H),6.44(s,1H),3.97(s,3H),3.85(s,3H).
Embodiment 46
(E)-2-[2-(2,4-dihydroxyl-phenyl)-vinyl]-6-hydroxyl-4-methoxyl group-methyl benzoate (7h)
Taking compound 6h as raw material, obtain compound 7h, white solid (87%) by the method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ7.65(s,1H),6.96(d,J＝14.5Hz,2H),6.67(d,J＝14.5Hz,1H),6.52(s,1H),6.44(s,1H),6.34(d,J＝8.5Hz,2H),6.19(s,1H),3.97(s,3H),3.81(s,3H).
Embodiment 47
(E)-6-[2-(2,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (8h)
Taking compound 7h as raw material, obtain compound 8h, white solid (47%) by the method reaction of embodiment 7.1H?NMR(500MHz,CDCl3)δ8.78(s,1H),7.65(s,1H),7.01(d,J＝14.0Hz,2H),6.70(s,1H),6.32(d,J＝14.0Hz,2H),6.20(s,1H),5.69(s,1H),5.54(t,J＝7.0Hz,1H),3.91(s,3H),3.83(s,3H),3.54(d,J＝7.0Hz2H),1.96(s,3H),1.87(s,3H).
Embodiment 48
(E)-6-[2-(2,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (9h)
Taking compound 8h as raw material, obtain compound 9h according to the method for embodiment 8, white solid (89%) 1HNMR (500MHz, CDCl3) δ 8.50 (s, 1H), 7.73 (s, 1H), 7.17 (d, J=10.0Hz, 2H), 6.76 (s, 1H), 6.34 (d, J=7.2Hz, 2H), 6.22 (s, 1H), 5.69 (s, 1H), 5.01 (s, 1H), 3.77 (s, 3H), 3.05 (s, 2H), 1.89 (s, 3H), 1.80 (s, 3H).
Embodiment 49
(E)-4-{2-[3-hydroxy-5-methyl oxygen base-4-(3-methyl but-2-ene base)-phenyl]-vinyl }-benzene-1,3-glycol (10h)
Taking compound 9h as raw material, obtain compound 10h according to the method for embodiment 9, white solid (94%) 1HNMR (500MHz, CDCl3) δ 7.69 (s, 1H), 7.19 (s, 1H), 6.89 (s, 1H), 6.60 (s, 1H), 6.56 (s, 1H), 6.35 (s, 1H), 6.29 (s, 1H), 6.21 (s, 1H), 5.92 (s, 1H), 5.67 (s, 1H), 5.39 (t, J=7.0Hz1H), 3.80 (s, 3H), 3.53 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.87 (s, 3H).
Embodiment 50
(E)-2,4-dimethoxy-6-[2-(6-methoxypyridine-3-yl)-vinyl] methyl benzoate (6i)
Taking 6-methoxypyridine-3-formaldehyde as raw material, obtain this compound, white solid (83%) with the similar method of embodiment 5.1H?NMR(500MHz,Chloroform)δ7.73(s,1H),7.65(s,1H),7.10(s,1H),6.89(s,1H),6.72(s,1H),6.60(d,J＝14.0Hz,2H),3.95(d,J＝5.6Hz,6H),3.84(d,J＝7.8Hz,6H).
Embodiment 51
(E)-2-hydroxyl-4-methoxyl group-6-[2-(6-methoxypyridine-3-yl)-vinyl] methyl benzoate (7i)
Taking 6i as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.74 (s, 1H), 7.65 (dd, J=7.5,1.5Hz, 1H), 7.09 (m, 3H), 6.81 (t, J=10.0Hz, 1H), 6.56 (d, J=8.0Hz, 1H), 6.50 – 6.48 (m, 1H), 3.97 (s, 3H), 3.84 (s, 3H).
Embodiment 52
(E)-2-hydroxyl-4-methoxyl group-6-[2-(6-methoxypyridine-3-yl)-vinyl]-3-(3-methyl but-2-ene base)-methyl benzoate (8i)
Taking 7i as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 7.77 (s, 1H), 7.70 (d, J=10.5Hz, 2H), 7.27 (m, 1H), 7.05 (m, 1H), 6.61 (d, J=16.0Hz, 2H), 5.40 (s, 1H), 3.97 (s, 3H), 3.83 (s, 6H), 3.46 (s, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 53
(E)-2-hydroxyl-4-methoxyl group-6-[2-(6-methoxypyridine-3-yl)-vinyl]-3-(3-methyl but-2-ene base)-phenylformic acid (9i)
Taking 8i as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 7.90 (s, 1H), 7.83 (s, 1H), 7.64 (s, 1H), 7.43 (s, 1H), 6.99 (s, 1H), 6.75 (s, 1H), 6.58 (s, 1H), 5.38 (s, 1H), 3.83 (s, 6H), 3.50 (s, 2H), 1.92 (s, 3H), 1.83 (s, 3H).
Embodiment 54
(E)-3-methoxyl group-5-[2-(6-methoxypyridine-3-yl)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10i)
Taking 9i as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 7.70 (s, 1H), 7.64 (s, 1H), 6.85 (d, J=8.6Hz, 2H), 6.56 (s, 1H), 6.45 (s, 1H), 6.39 (s, 1H), 5.85 (s, 1H), 5.40 (t, J=7.0Hz, 1H), 3.83 (s, 3H), 3.73 (s, 3H), 3.42 (d, J=7.0Hz, 2H), 1.90 (s, 3H), 1.81 (s, 3H).
Embodiment 55
(E)-2-[2-(4,6-dimethoxy-pyridine-3-yl)-vinyl]-4,6-dimethoxy p-methyl (6j)
For raw material, obtain this compound, white solid (83%) with the similar method of embodiment 5 with 4,6-dimethoxy-pyridine-3-formaldehyde.1H?NMR(500MHz,Chloroform)δ7.64(s,1H),6.94(s,1H),6.87(s,1H),6.81(s,1H),6.72(s,1H),6.34(s,1H),3.98–3.88(m,12H),3.85(s,3H).
Embodiment 56
(E)-2-[2-(4,6-dimethoxy-pyridine-3-yl)-vinyl]-6-hydroxyl-4-methoxyl group-methyl benzoate (7j)
Taking 7i as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.55 (s, 1H), 7.00 (s, 1H), 6.76 (s, 1H), 6.56 (s, 1H), 6.41 (s, 1H), 6.33 (s, 1H), 3.89 (s, 6H), 3.85 (s, 6H).
Embodiment 57
(E)-6-[2-(4,6-dimethoxy-pyridine-3-yl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate (8j)
Taking 7j as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 8.55 (s, 1H), 7.76 (s, 1H), 7.16 (s, 1H), 6.97 (s, 1H), 6.67 (s, 1H), 6.48 (s, 1H), 5.51 (t, J=7.0Hz, 1H), 3.98 (s, 3H), 3.90 (s, 6H), 3.80 (s, 3H), 3.48 (s, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 58
(E)-6-[2-(4,6-dimethoxy-pyridine-3-yl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid (9j)
Taking 8j as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 7.77 (s, 1H), 7.51 (s, 1H), 7.15 (s, 1H), 6.83 (s, 1H), 6.74 (s, 1H), 6.47 (s, 1H), 5.41 (t, J=7.0Hz, 1H), 3.89 (d, J=5.7Hz, 6H), 3.83 (s, 3H), 3.52 (s, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 59
(E)-5-(2-(4,6-dimethoxy-pyridine-3-yl) vinyl]-3-methoxyl group-2-(3-methyl but-2-ene base)-phenol (10j)
Taking 9j as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 7.66 (s, 1H), 7.14 (s, 1H), 6.93 (s, 1H), 6.46 (d, J=0.8Hz, 2H), 6.33 (s, 1H), 5.98 (s, 1H), 5.01 (s, 1H), 3.94 (s, 3H), 3.88 (s, 3H), 3.83 (s, 3H), 3.06 (s, 2H), 1.88 (s, 3H), 1.80 (s, 3H).
Embodiment 60
(E)-2,4-dimethoxy-6-[2-(2-methoxypyridine-4-yl)-vinyl] methyl benzoate (6k)
Taking 2-methoxypyridine-4-formaldehyde as raw material, obtain this compound, white solid (83%) with the similar method of embodiment 5.1H?NMR(500MHz,Chloroform)δ7.65(s,1H),7.39(s,1H),7.05(s,1H),6.81(s,1H),6.73(s,1H),6.62(s,1H),6.34(s,1H),3.96(s,6H),3.86(s,6H).
Embodiment 61
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxypyridine-4-yl)-vinyl] methyl benzoate (7k)
Taking 6k as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.64 (m, 2H), 6.82 (m, 2H), 6.62 (s, 1H), 6.52 (s, 1H), 6.35 (s, 1H), 3.96 (s, 3H), 3.89 (s, 3H), 3.85 (s, 3H).
Embodiment 62
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxypyridine-4-yl)-vinyl]-3-(3-methyl but-2-ene base)-methyl benzoate (8k)
Taking 7k as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 9.04 (s, 1H), 7.69-7.51 (m, 2H), 6.92 (d, J=7.5Hz, 2H), 6.75 (s, 1H), 6.30 (s, 1H), 5.42 (t, J=7.0Hz, 1H), 3.95 (s, 3H), 3.90 (s, 3H), 3.75 (s, 3H), 3.56 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 63
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxypyridine-4-yl)-vinyl]-3-(3-methyl but-2-ene base)-phenylformic acid (9k)
Taking 8k as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 7.84 – 7.59 (m, 3H), 6.99-6.76 (m, 3H), 6.29 (s, 1H), 5.40 (s, J=7.0Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.50 (s, J=7.0Hz, 2H), 1.92 (s, 3H), 1.83 (s, 3H).
Embodiment 64
(E)-3-methoxyl group-5-[2-(2-methoxypyridine-4-yl)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10k)
Taking 9k as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 7.65-7.38 (m, 2H), 7.21 (s, 2H), 6.84 (s, 1H), 6.48 (d, J=9.0Hz, 2H), 6.29 (s, 1H), 5.84 (s, 1H), 5.41 (s, J=7.0Hz, 1H), 3.87 (s, 3H), 3.79 (s, 3H), 3.44 (s, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 65
(E)-2-[2-(2,5-dimethoxy-pyridine-4-yl)-vinyl]-4,6-dimethoxy-methyl benzoate (6l)
For raw material, obtain this compound, white solid (83%) with the similar method of embodiment 5 with 2,5-dimethoxy-pyridine-4-formaldehyde.1H?NMR(500MHz,Chloroform)δ7.41(d,J＝8.0Hz,2H),6.92(s,1H),6.79(d,J＝8.0Hz,2H),6.62(s,1H),3.96(s,6H),3.91–3.83(m,9H).
Embodiment 66
(E)-2-[2-(2,5-dimethoxy-pyridine-4-yl)-vinyl]-6-hydroxyl-4-methoxyl group-methyl benzoate (7l)
Taking 6l as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.48 (s, 1H), 7.35 (s, 1H), 6.92 (s, 1H), 6.87 (s, 1H), 6.63 (s, 1H), 6.50 (s, 1H), 3.97 (s, 3H), 3.91 – 3.83 (m, 9H).
Embodiment 67
(E)-6-[2-(2,5-dimethoxy-pyridine-4-yl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (8l)
Taking 7l as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 7.54-7.44 (m, 2H), 7.32 (s, 1H), 6.90 (d, J=16.0Hz, 2H), 6.67 (s, 1H), 5.40 (s, J=7.0Hz, 1H), 3.97 (s, 3H), 3.89 (s, 6H), 3.83 (s, 3H), 3.51 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 68
(E)-6-[2-(2,5-dimethoxy-pyridine-4-yl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (9l)
Taking 8l as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 7.85 (s, 1H), 7.77 (s, 1H), 7.41 (s, 1H), 6.98 (s, 2H), 6.72 (s, 1H), 5.47 (s, J=7.0Hz, 1H), 3.88 (s, 3H), 3.82 (s, 6H), 3.49 (s, J=7.0Hz, 2H), 1.91 (s, 3H), 1.83 (s, 3H).
Embodiment 69
(E)-5-(2-(2,5-dimethoxy-pyridine-4-yl) vinyl]-3-methoxyl group-2-(3-methyl but-2-ene base)-phenol
Taking 9l as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 7.51 (s, 1H), 7.07 (s, 2H), 6.94 (s, 1H), 6.52 (s, 1H), 6.45 (s, 1H), 5.86 (s, 1H), 5.44 (s, J=7.0Hz, 1H), 3.88 (s, 6H), 3.80 (s, 3H), 3.46 (s, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 70
(E)-2,4-dimethoxy-6-[2-(1H-pyrroles-3-yl)-vinyl] methyl benzoate (6m)
Taking 1H-pyrroles-3-formaldehyde as raw material, obtain this compound with the similar method of embodiment 5, white solid 1H NMR (500MHz, Chloroform) δ 7.24 (s, 1H), 6.88 (t, J=17.5Hz, 2H), 6.68 (s, 1H), 6.58 (t, J=17.5Hz, 2H), 6.43 (s, 1H), 6.17 (s, 1H), 3.95 (s, 6H), 3.85 (s, 3H).
Embodiment 71
(E)-2-hydroxyl-4-methoxyl group-6-[2-(1H-pyrroles-3-yl)-vinyl] methyl benzoate (7m)
Taking 6m as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.34 (d, J=6.0Hz, 2H), 6.97 (s, 1H), 6.77 (s, 1H), 6.55 (s, 1H), 6.43-6.41 (m, 2H), 6.22 (s, 1H), 3.96 (s, 3H), 3.85 (s, 3H).
Embodiment 72
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-3-yl) vinyl] methyl benzoate (8m)
Taking 7m as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 7.56 (s, 1H), 7.12-7.00 (m, 3H), 6.67 (d, J=10.5Hz, 2H), 6.36 (s, 1H), 6.13 (s, 1H), 5.42 (t, J=7.0Hz, 1H), 3.97 (s, 3H), 3.83 (s, 3H), 3.58 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 73
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-3-yl) vinyl] phenylformic acid (9m)
Taking 8m as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 7.76 (s, 1H), 7.45 (s, 1H), 7.23 (s, 1H), 6.93 (d, J=18.2Hz, 2H), 6.73 (s, 1H), 6.32 (s, 1H), 6.23 (s, 1H), 5.45 (s, 1H), 3.80 (s, 3H), 3.58 (s, 2H), 1.91 (s, 3H), 1.83 (s, 3H).
Embodiment 74
(E)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-[2-(1H-pyrroles-3-yl)-vinyl]-phenol (10m)
Taking 9m as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 7.34 (s, 1H), 7.06 (s, 1H), 6.95 (s, 1H), 6.68 (s, 1H), 6.45 (t, J=7.3Hz, 3H), 6.19 (s, 1H), 5.82 (s, 1H), 5.54 (t, J=7.0Hz, 1H), 3.82 (s, 3H), 3.50 (d, J=7.0Hz, 2H), 1.90 (s, 3H), 1.82 (s, 3H).
Embodiment 75
(E)-2,4-dimethoxy-6-[2-(5-methoxyl group-1H-pyrroles-3-yl)-vinyl] methyl benzoate (6n)
Taking 5-methoxyl group-1H-pyrroles-3-formaldehyde as raw material, obtain this compound with the similar method of embodiment 5, white solid 1H NMR (500MHz, Chloroform) δ 7.26 (s, 1H), 7.04 (s, 1H), 6.71 (s, 1H), 6.65 (s, 1H), 6.60 (s, 1H), 6.48 (s, 1H), 5.27 (s, 1H), 3.96 (s, 6H), 3.85 (s, 6H).
Embodiment 76
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-1H-pyrroles-3-yl)-vinyl] methyl benzoate (7n)
Taking 6n as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.34-7.11 (m, 2H), 6.67 (d, J=15.5Hz, 2H), 6.49 (d, J=16.5Hz, 2H), 5.53 (s, 1H), 3.97 (s, 3H), 3.85 (s, 6H).
Embodiment 77
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-1H-pyrroles-3-yl)-vinyl]-3-(3-methyl but-2-ene base)-methyl benzoate
Taking 7n as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 7.21 (s, 1H), 7.08 (d, J=18.0Hz, 2H), 6.69 (s, 2H), 6.45 (s, 1H), 5.77 (s, 1H), 5.31 (t, J=7.0Hz, 1H), 3.97 (s, 3H), 3.83 (s, 6H), 3.55 (d, J=7.0Hz, 2H), 1.88 (s, 3H), 1.79 (s, 3H).
Embodiment 78
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-1H-pyrroles-3-yl)-vinyl]-3-(3-methyl but-2-ene base)-phenylformic acid (9n)
Taking 8n as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 7.78 (s, 1H), 7.03 (dd, J=16.0,7.0Hz, 2H), 6.81-6.74 (m, 2H), 6.54 (s, 1H), 5.74 (s, 1H), 5.48 (t, J=7.0Hz, 1H), 5.33 (s, 1H), 3.84 (s, 3H), 3.80 (s, 3H), 3.58 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.83 (s, 3H).
Embodiment 79
(E)-3-methoxyl group-5-[2-(5-methoxyl group-1H-pyrroles-3-yl)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10n)
Taking 9n as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 7.36 (s, 1H), 7.06 (s, 1H), 6.67 (s, 1H), 6.59 (s, 1H), 6.50 (s, 1H), 6.42 (s, 1H), 5.82 (s, 1H), 5.54 (s, J=7.0Hz, 1H), 5.29 (s, 1H), 3.83 (s, 6H), 3.50 (s, J=7.0Hz, 2H), 1.90 (s, 3H), 1.82 (s, 3H).
Embodiment 80
(E)-2-(2-furans-3-base-vinyl)-4,6-dimethoxy p-methyl (6o)
Taking furans-3-formaldehyde as raw material, obtain this compound with the similar method of embodiment 5, white solid 1HNMR (500MHz, Chloroform) δ 7.93 (s, 3H), 7.40 – 7.25 (m, 3H), 7.12 (s, 1H), 7.05 (s, 1H), 6.70 (s, 1H), 6.61 (s, 2H), 3.96 (s, 6H), 3.85 (s, 3H).
Embodiment 81
(E)-2-(2-furans-3-base-vinyl)-6-hydroxyl-4-methoxyl group-methyl benzoate (7o)
Taking 6o as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.93 (s, 1H), 7.40 (d, J=15.0Hz, 1H), 7.32 (dt, J=15.0,7.5Hz, 2H), 7.26 (s, 1H), 6.77-6.66 (m, 2H), 6.51 (s, 1H), 3.97 (s, 3H), 3.85 (s, 3H).
Embodiment 82
(E)-6-(2-furans-3-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (8o)
Taking 7o as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 7.89 (s, 1H), 7.75 (s, 1H), 7.32 (s, 1H), 7.20 (s, 2H), 6.71 (s, 1H), 6.62 (s, 1H), 5.45 (s, J=7.0Hz, 1H), 3.97 (s, 3H), 3.80 (s, 3H), 3.54 (s, J=7.0Hz, 2H), 1.91 (s, 3H), 1.83 (s, 3H).
Embodiment 83
(E)-6-(2-furans-3-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (9o)
Taking 8o as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 8.02 (s, 1H), 7.82 (s, 1H), 7.46 (s, 1H), 7.34 (s, 1H), 7.24 (s, 1H), 6.72 (s, 2H), 5.40 (t, J=7.0Hz, 1H), 3.83 (s, 3H), 3.57 (d, J=7.0Hz, 2H), 1.92 (s, 3H), 1.83 (s, 3H).
Embodiment 84
(E)-5-(2-furans-3-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol (10o)
Taking 9o as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 7.92 (s, 1H), 7.35 (s, 2H), 7.09 (s, 1H), 6.72 (s, 1H), 6.46 (s, 2H), 5.82 (s, 1H), 5.54 (t, J=7.0Hz, 1H), 3.82 (s, 3H), 3.51 (d, J=7.0Hz2H), 1.90 (s, 3H), 1.82 (s, 3H).
Embodiment 85
(E)-2,4-dimethoxy-6-[2-(4-methoxyl group furans-3-yl)-vinyl] methyl benzoate (6p)
Taking 4-methoxyl group-furans-3-formaldehyde as raw material, obtain this compound with the similar method of embodiment 5, white solid 1H NMR (500MHz, Chloroform) δ 7.86 (s, 1H), 7.28 (s, 2H), 6.73 (s, 1H), 6.61 (s, 1H), 6.52 (s, 1H), 3.96 (s, 6H), 3.85 (s, 6H).
Embodiment 86
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group-furans-3-yl)-vinyl] methyl benzoate (7p)
Taking 6p as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.90 (s, 1H), 7.33 (s, 2H), 6.66 (s, 1H), 6.52 (s, 2H), 3.97 (s, 3H), 3.86 (s, 6H).
Embodiment 87
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group furans-3-yl)-vinyl]-3-(3-methyl but-2-ene base)-methyl benzoate (8p)
Taking 7p as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 9.04 (s, 1H), 7.80 (s, 1H), 7.19 (d, J=26.4Hz, 2H), 6.68 (s, 1H), 6.57 (s, 1H), 5.45 (t, J=7.0Hz, 1H), 3.98 (s, 3H), 3.86 (s, 3H), 3.80 (s, 3H), 3.58 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 88
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group furans-3-yl)-vinyl]-3-(3-methyl but-2-ene base)-phenylformic acid (9p)
Taking 8p as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 9.23 (s, 1H), 7.86 (s, 1H), 7.53 (s, 1H), 7.03 (s, 1H), 6.75 (s, 1H), 6.56 (s, 1H), 5.50 (t, J=7.0Hz, 1H), 3.86 (s, 3H), 3.80 (s, 3H), 3.61 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 89
(E)-3-methoxyl group-5-[2-(4-methoxyl group furans-3-yl)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10p)
Taking 9p as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 7.82 (s, 1H), 7.37 (s, 1H), 7.13 (s, 1H), 6.50 (s, 2H), 6.43 (s, 1H), 5.82 (s, 1H), 5.55 (s, 1H), 3.84 (s, 6H), 3.51 (s, 2H), 1.90 (s, 3H), 1.82 (s, 3H).
Embodiment 90
(E)-2-[2-(2H-imidazol-4 yl)-vinyl]-4,6-dimethoxy p-methyl (6q)
Taking 2H-imidazoles-4-formaldehyde as raw material, obtain this compound with the similar method of embodiment 5, white solid 1H NMR (500MHz, Chloroform) δ 7.07 (s, 2H), 6.90 – 6.70 (m, 3H), 6.71 (s, 1H), 6.71 (s, 1H), 6.62 (s, 1H), 5.18 (s, 2H), 3.95 (s, 6H), 3.84 (s, 3H).
Embodiment 91
(E)-2-hydroxyl-6-[2-(2H-imidazol-4 yl)-vinyl]-4-methoxyl group-methyl benzoate (7q)
Taking 6q as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.17 (s, 2H), 6.95 (s, 1H), 6.64 (s, 1H), 6.51 (s, 1H), 5.20 (s, 2H), 3.95 (s, 3H), 3.84 (s, 3H).
Embodiment 92
(E)-2-hydroxyl-6-[2-(2H-imidazol-4 yl)-vinyl]-4-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (8q)
Taking 7q as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 7.76 (s, 33H), 6.68 (s, 2H), 6.63 (s, 1H), 6.54 (s, 2H), 5.45 (t, J=7.0Hz, 1H), 5.16 (s, 2H), 3.96 (s, 3H), 3.79 (s, 3H), 3.54 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 93
(E)-2-hydroxyl-6-[2-(2H-imidazol-4 yl)-vinyl]-4-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (9q)
Taking 8q as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 7.80 (s, 1H), 7.15 (s, 1H), 6.74 (s, 2H), 6.46 (s, 1H), 5.39 (t, J=7.0Hz, 1H), 5.21 (s, 2H), 3.82 (s, 3H), 3.57 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.83 (s, 3H).
Embodiment 94
(E)-5-[2-(2H-imidazol-4 yl) vinyl]-3-methoxyl group-2-(3-methyl but-2-ene base)-phenol (10q)
Taking 9q as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 6.92 (s, 1H), 6.74 (s, 1H), 6.58 (s, 1H), 6.51 (d, J=7.8Hz, 2H), 5.81 (s, 1H), 5.57 (s, 1H), 5.19 (s, 2H), 3.81 (s, 3H), 3.55 (s, 2H), 1.90 (s, 3H), 1.81 (s, 3H).
Embodiment 95
(E)-2,4-dimethoxy-6-[2-(5-methoxyl group-2H-imidazol-4 yl)-vinyl] methyl benzoate (6r)
Taking 5-methoxyl group-2H-imidazoles-4-formaldehyde as raw material, obtain this compound with the similar method of embodiment 5, white solid 1H NMR (500MHz, Chloroform) δ 7.09 (s, 1H), 6.68 (s, 1H), 6.61 (s, 1H), 5.90 (s, 1H), 5.23 (s, 2H), 3.94 (s, 6H), 3.86 (s, 6H).
Embodiment 96
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-2H-imidazol-4 yl)-vinyl] methyl benzoate (7r)
Taking 6r as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.12 (s, 1H), 6.59 (s, 1H), 6.51 (s, 1H), 6.10 (s, 1H), 5.27 (s, 2H), 3.95 (s, 3H), 3.84 (s, 6H).
Embodiment 97
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-2H-imidazol-4 yl)-vinyl]-3-(3-methyl but-2-ene base)-methyl benzoate (8r)
Taking 7r as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 7.79 (s, 1H), 6.83 (s, 1H), 6.63 (s, 1H), 6.51 (s, 1H), 5.40 (t, J=7.0Hz, 1H), 5.22 (s, 2H), 3.95 (s, 3H), 3.89 (s, 3H), 3.82 (s, 3H), 3.55 (d, J=7.0Hz, 2H), 1.90 (s, 3H), 1.82 (s, 3H).
Embodiment 98
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-2H-imidazol-4 yl)-vinyl]-3-(3-methyl but-2-ene base)-methyl benzoate (9r)
Taking 8r as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 7.77 (s, 1H), 7.03 (s, 1H), 6.67 (s, 2H), 5.41 (t, J=7.0Hz, 1H), 5.24 (s, 2H), 3.88 (s, 3H), 3.82 (s, 3H), 3.55 (d, J=7.0Hz, 2H), 1.90 (s, 3H), 1.81 (s, 3H).
Embodiment 99
(E)-3-methoxyl group-5-[2-(5-methoxyl group-2H-imidazol-4 yl)-vinyl]-2-(3-methyl but-2-ene base)-phenol
Taking 9r as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 6.94 (s, 1H), 6.67 (s, 1H), 6.58 (s, 1H), 6.53 (s, 1H), 5.86 (s, 1H), 5.41 (t, J=7.0Hz1H), 5.28 (s, 2H), 3.89 (s, 3H), 3.73 (s, 3H), 3.63 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 100
(E)-2,4-dimethoxy-6-(2-thiazole-5-base-vinyl)-methyl benzoate (6s)
Taking thiazole-5-formaldehyde as raw material, obtain this compound, white solid 1HNMR (500MHz with the similar method of embodiment 5, Chloroform) δ 8.59 (s, 1H), 7.35 (s, 1H), 7.26 (s, 2H), 6.73 (s, 1H), 6.61 (s, 1H), 3.95 (s, 6H), 3.86 (s, 3H).
Embodiment 101
(E)-2-hydroxyl-4-methoxyl group-6-(2-thiazole-5-base-vinyl)-methyl benzoate (7s)
Taking 6s as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 8.62 (s, 1H), 7.48 (s, 1H), 7.29 (s, 2H), 6.60 (s, 1H), 6.43 (s, 1H), 3.96 (s, 3H), 3.86 (s, 3H).
Embodiment 102
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazole-5-base-vinyl)-methyl benzoate
Taking 7s as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 9.04 (s, 1H), 8.94 (s, 1H), 7.38 (s, 1H), 7.28 (s, 1H), 7.20 (s, 1H), 6.68 (s, 1H), 5.50 (t, J=7.0Hz, 1H), 3.97 (s, 3H), 3.83 (s, 3H), 3.57 (d, J=7.0Hz, 2H), 1.90 (s, 3H), 1.81 (s, 3H).
Embodiment 103
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazole-5-base-vinyl)-phenylformic acid (9s)
Taking 8s as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 8.90 (s, 1H), 7.59 (s, 1H), 7.35 (s, 1H), 7.18 (s, 2H), 6.75 (s, 1H), 5.40 (t, J=7.0Hz, 1H), 3.83 (s, 3H), 3.60 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 104
(E)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-(2-thiazole-5-base-vinyl)-phenol (10s)
Taking 9s as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 8.93 (s, 1H), 7.39 (s, 1H), 7.22 (s, 2H), 6.50 (s, 2H), 5.93 (s, 1H), 5.39 (t, J=7.0Hz, 1H), 3.80 (s, 3H), 3.53 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 105
(E)-2,4-dimethoxy-6-[2-(4-methoxyl group-thiazole-5-yl)-vinyl] methyl benzoate
Taking 4-methoxyl group-thiazole-5-formaldehyde as raw material, obtain this compound with the similar method of embodiment 5, white solid (6t) 1H NMR (500MHz, Chloroform) δ 8.73 (s, 1H), 7.20 (s, 1H), 6.97 (s, 1H), 6.70 (s, 1H), 6.60 (s, 1H), 4.10 (s, 3H), 3.96 (s, 6H), 3.85 (s, 3H).
Embodiment 106
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group-thiazole-5-yl)-vinyl] methyl benzoate (7t)
Taking 6t as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 9.04 (s, 1H), 7.05 (s, 2H), 6.63 (s, 1H), 6.50 (s, 1H), 4.11 (s, 3H), 3.97 (s, 3H), 3.85 (s, 3H).
Embodiment 107
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group-thiazole-5-yl)-vinyl]-3-(3-methyl but-2-ene base)-methyl benzoate (8t)
Taking 7t as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 9.10 (s, 1H), 9.04 (s, 1H), 7.38 – 7.06 (m, 2H), 7.05 (s, 1H), 6.67 (s, 1H), 5.46 (t, J=7.0Hz, 1H), 4.12 (s, 3H), 3.98 (s, 3H), 3.81 (s, 3H), 3.58 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 108
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group-thiazole-5-yl)-vinyl]-3-(3-methyl but-2-ene base)-phenylformic acid (9t)
Taking 8t as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 9.04 (s, 2H), 7.27 (s, 1H), 6.83 (s, 2H), 5.51 (t, J=7.0Hz, 1H), 4.12 (s, 3H), 3.83 (s, 3H), 3.57 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 109
(E)-3-methoxyl group-5-[2-(4-methoxyl group-thiazole-5-yl)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10t)
Taking 9t as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 8.75 (s, 1H), 7.33 (s, 1H), 7.14 (s, 1H), 6.49 (s, 1H), 6.42 (s, 1H), 5.82 (s, 1H), 5.54 (t, J=7.0Hz, 1H), 4.08 (s, 3H), 3.82 (s, 3H), 3.50 (d, J=7.0Hz, 2H), 1.90 (s, 3H), 1.82 (s, 3H).
Embodiment 110
(E)-2,4-dimethoxy-6-(2-oxazole-5-base-vinyl)-methyl benzoate (6u)
Taking oxazole-5-formaldehyde as raw material, obtain this compound, white solid 1HNMR (500MHz with the similar method of embodiment 5, Chloroform) δ 7.90 (s, 1H), 7.09 (s, 2H), 6.98 (s, 1H), 6.71 (s, 1H), 6.61 (s, 1H), 3.96 (s, 6H), 3.85 (s, 3H).
Embodiment 111
(E)-2-hydroxyl-4-methoxyl group-6-(2-oxazole-5-base-vinyl)-methyl benzoate (7u)
Taking 6u as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.90 (s, 1H), 7.35 (s, 1H), 7.09 (s, 1H), 7.03 (s, 1H), 6.65 (s, 1H), 6.51 (s, 1H), 3.97 (s, 3H), 3.85 (s, 3H).
Embodiment 112
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-5-base-vinyl)-methyl benzoate (8u)
Taking 7u as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 7.90 (s, 1H), 7.77 (s, 1H), 7.09 (s, 2H), 6.97 (s, 1H), 6.61 (s, 1H), 5.46 (s, 1H), 3.97 (s, 3H), 3.80 (s, 3H), 3.55 (s, 2H), 1.91 (s, 3H), 1.83 (s, 3H).
Embodiment 113
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-5-base-vinyl)-phenylformic acid (9u)
Taking 8u as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 7.90 (s, 1H), 7.77 (s, 1H), 7.19 (s, 1H), 7.09 (s, 1H), 7.01 (s, 1H), 6.73 (s, 1H), 5.41 (t, J=7.0Hz, 1H), 3.83 (s, 3H), 3.55 (d, J=7.0Hz, 2H), 1.90 (s, 3H), 1.82 (s, 3H).
Embodiment 114
(E)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-(2-oxazole-5-base-vinyl)-phenol (10u)
Taking 9u as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 7.90 (s, 1H), 7.23 – 7.07 (m, 3H), 6.49 (s, 1H), 6.43 (s, 1H), 5.82 (s, 1H), 5.54 (t, J=7.0Hz, 1H), 3.82 (s, 3H), 3.51 (d, J=7.0Hz, 2H), 1.90 (s, 3H), 1.82 (s, 3H).
Embodiment 115
(E)-2,4-dimethoxy-6-[2-(2-methoxyl group-oxazole-5-yl)-vinyl] methyl benzoate (6v)
Taking 2-methoxyl group-oxazole-5-formaldehyde as raw material, obtain this compound with the similar method of embodiment 5, white solid 1H NMR (500MHz, Chloroform) δ 7.16 (s, 2H), 6.87 (s, 1H), 6.63 (s, 1H), 6.51 (s, 1H), 3.99 – 3.89 (m, 9H), 3.86 (s, 3H).
Embodiment 116
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxyl group-oxazole-5-yl)-vinyl] methyl benzoate (7v)
Taking 6v as raw material, obtain this compound with the similar method of embodiment 6, white solid 1H NMR (500MHz, Chloroform) δ 7.30 (s, 1H), 7.05 (s, 1H), 6.87 (s, 1H), 6.53 (s, 1H), 6.41 (s, 1H), 3.96 (s, 3H), 3.92 (s, 3H), 3.86 (s, 3H).
Embodiment 117
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxyl group-oxazole-5-yl)-vinyl]-3-(3-methyl but-2-ene base)-methyl benzoate (8v)
Taking 7v as raw material, obtain this compound with the similar method of embodiment 7, white solid 1H NMR (500MHz, Chloroform) δ 7.77 (s, 1H), 6.96 (s, 2H), 6.81 (s, 1H), 6.60 (s, 1H), 5.46 (t, J=7.0Hz, 2H), 3.97 (s, 3H), 3.91 (s, 3H), 3.80 (s, 3H), 3.54 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.83 (s, 3H).
Embodiment 118
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxyl group-oxazole-5-yl)-vinyl]-3-(3-methyl but-2-ene base)-phenylformic acid (9v)
Taking 8v as raw material, obtain this compound with the similar method of embodiment 8, white solid 1H NMR (500MHz, Chloroform) δ 7.82 (s, 1H), 7.38 (s, 1H), 6.97 (s, 1H), 6.83 (s, 1H), 6.73 (s, 1H), 5.40 (t, J=7.0Hz, 1H), 3.92 (s, 3H), 3.83 (s, 3H), 3.57 (d, J=7.0Hz, 2H), 1.92 (s, 3H), 1.83 (s, 3H).
Embodiment 119
(E)-3-methoxyl group-5-[2-(2-methoxyl group-oxazole-5-yl)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10v)
Taking 9v as raw material, obtain this compound with the similar method of embodiment 9, white solid 1H NMR (500MHz, Chloroform) δ 7.08 (s, 1H), 7.00 (s, 1H), 6.87 (s, 1H), 6.45 (s, 2H), 5.82 (s, 1H), 5.54 (d, J=7.0Hz, 2H), 3.91 (s, 3H), 3.82 (s, 3H), 3.50 (d, J=7.0Hz, 2H), 1.90 (s, 3H), 1.82 (s, 3H).
Embodiment 120
2,4-dimethoxy-6-thiazol-2-yl ethynyl-methyl benzoate (11a)
Under normal temperature, compound 6a (40g, 0.131mol) is dissolved in dehydrated alcohol, add bromine (42g, 0.262mol), be heated to 70 DEG C, 2h, after cold normal temperature processed, successively by adding KOH (22g, 0.139mmol), finish and be warming up to 80 DEG C, after 5h, stop reaction, dehydrated alcohol is steamed, acetic acid ethyl dissolution system, saturated common salt washing, anhydrous magnesium sulfate drying spends the night.Filter, revolve to steam and remove ethyl acetate, residuum sherwood oil: ethyl acetate=7:1 crosses silicagel column, obtain compound 11a (31.2g, 80%) white solid .1H NMR (500MHz, Chloroform) δ 7.59 (s, 1H), 7.38 (s, 1H), 7.28 (s, 1H), 6.61 (s, 1H), 3.95 (s, 9H).
Embodiment 121
(Z)-2,4-dimethoxy-6-(2-thiazol-2-yl vinyl) methyl benzoate (12a)
Compound 11a (25g, 0.072mol) is dissolved in dehydrated alcohol, adds Pd/CaCO3, be placed in microwave device, microwave condition is 100 DEG C, 30w, and 60psi, stops reaction after 2h, dehydrated alcohol is steamed, acetic acid ethyl dissolution system, saturated common salt washing, anhydrous magnesium sulfate drying spends the night.Filter, revolve to steam and remove ethyl acetate, residuum sherwood oil: ethyl acetate=10:1 crosses silicagel column, obtains compound 12a (21.3g, 85%) white solid 1H NMR (500MHz, CDCl3) δ 7.75 (s, 1H), 7.47 (s, 1H), 6.99 (d, J=16.0Hz, 2H), 6.65 (d, J=16.0Hz, 2H), 3.94 (s, 6H), 3.85 (s, 3H).
Embodiment 122
(Z)-2-hydroxyl-4-methoxyl group-6-(2-thiazol-2-yl-vinyl)-methyl benzoate (13a)
Taking compound 12a as raw material, obtain compound 13a according to the similar method of embodiment 6, white solid (95%) 1H NMR (500MHz, CDCl3) δ 7.75 (d, J=7.5Hz, 1H), 7.52 – 7.28 (m, 3H), 7.28 – 7.18 (m, 1H), 6.67 (s, 1H), 6.52 (s, 1H), 3.97 (s, 3H), 3.85 (s, 3H).
Embodiment 123
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-methyl benzoate (14a);
Taking compound 13a as raw material, obtain compound 14a according to the method for embodiment 7, white solid (56%).1H?NMR(500MHz,CDCl3)δ9.04(s,1H),7.76(s,1H),7.49(s,1H),7.40(s,1H),7.23(s,1H),6.65(s,1H),5.50(t,J＝7.5Hz,1H),3.95(s,3H),3.80(s,3H),3.58(d,J＝7.5Hz,2H),1.91(s,3H),1.80(s,3H).
Embodiment 124
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-phenylformic acid (15a);
Taking compound 14a as raw material, obtain compound 15a according to the method for embodiment 8, white solid (80%).1H?NMR(500MHz,CDCl3)δ8.78(s,1H),7.76(s,1H),7.49(s,1H),7.39(s,1H),7.24(s,1H),6.74(s,1H),5.49(t,J＝7.5Hz,1H),3.80(s,3H),3.59(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 125
(Z)-3-methoxyl group-2-(3-methyl but-2-ene base)-5-(2-thiazol-2-yl-vinyl)-phenol (16a);
Taking compound 15a as raw material, obtain compound 16a according to the method for embodiment 9, white solid (88%).1H?NMR(500MHz,CDCl3)δ7.76(s,1H),7.48(s,1H),7.34(s,1H),7.07(s,1H),6.62(s,1H),6.57(s,1H),5.87(s,1H),5.44(t,J＝7.5Hz,1H),3.73(s,3H),3.64(d,J＝7.5Hz,2H),1.91(s,3H),1.83(s,3H).
Embodiment 126
2,4-dimethoxy-6-imidazoles-2-ethyl-acetylene base-methyl benzoate (11b)
Obtain compound 11b taking 6b as raw material according to the method for embodiment 120, white solid (87%) 1H NMR (500MHz, Chloroform) δ 7.30 (s, 2H), 7.12 (d, J=10.5Hz, 2H), 6.62 (t, J=10.5Hz, 1H), 5.96 (s, 1H), 3.95 (s, 9H).
Embodiment 127
(Z)-2,4-dimethoxy-6-(2 – imidazoles-2-base vinyl) methyl benzoate (12b)
Taking compound 11b as raw material, obtain compound 12b according to the method for embodiment 121, white solid (87%) 1H NMR (500MHz, CDCl3) δ 7.65 (s, 1H), 7.07-6.90 (m, 2H), 6.85 (d, J=12.0Hz, 2H), 6.68 (s, 1H), 6.63 (s, 1H), 6.50 (s, 1H), 3.95 (d, J=8.5Hz, 6H), 3.86 (s, 3H).
Embodiment 128
(Z)-2-hydroxyl-6-[2-(1H-imidazoles-2-yl)-vinyl]-4-methoxyl group-methyl benzoate (13b)
Taking compound 12b as raw material, obtain compound 13b according to the similar method of embodiment 6, white solid (95%) 1H NMR (500MHz, CDCl3) δ 7.65 (s, 1H), 7.11 – 7.03 (m, 3H), 6.60 (s, 1H), 6.50 (d, J=6.5Hz, 2H), 3.97 (s, 3H), 3.85 (s, 3H).
Embodiment 129
(Z)-2-hydroxyl-6-[2-(1H-imidazoles-2-yl)-vinyl]-4-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (14b)
Taking compound 13b as raw material, obtain compound 14b according to the method for embodiment 7, white solid (60%).1H?NMR(500MHz,CDCl3)δ9.04(s,1H),7.65(s,1H),7.25(s,2H),7.11(d,J＝6.8Hz,2H),6.72(s,1H),6.51(s,1H),5.48(s,1H),3.96(s,3H),3.74(s,3H),3.66(s,2H),1.92(s,3H),1.83(s,3H).
Embodiment 130
(Z)-2-hydroxyl-6-[2-(1H-imidazoles-2-yl)-vinyl]-4-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (15b)
Taking compound 14b as raw material, obtain compound 15b according to the method for embodiment 8, white solid (89%).1H?NMR(500MHz,CDCl3)δ8.75(s,1H),7.65(s,1H),7.18(d,J＝16.0Hz,2H),7.12-6.81(m,2H),6.50(s,1H),5.47(s,1H),3.74(s,3H),3.67(s,2H),1.92(s,3H),1.83(s,3H).
Embodiment 131
(Z)-5-[2-(1H-imidazoles-2-yl) vinyl]-3-methoxyl group-2-(3-methyl but-2-ene base)-phenol (16b)
Taking compound 15b as raw material, obtain compound 16b according to the method for embodiment 9, white solid (93%).1H?NMR(500MHz,CDCl3)δ7.65(s,1H),7.15(s,1H),7.10-6.95(m,2H),6.51(d,J＝8.0Hz,2H),6.45(s,1H),5.83(s,1H),5.51(s,1H),3.82(s,3H),3.54(s,2H),1.90(s,3H),1.82(s,3H).
Embodiment 132
2,4-dimethoxy-6-oxazole-2-ethyl-acetylene base-methyl benzoate (11c)
Obtain compound 11c taking 6c as raw material according to the method for embodiment 120, white solid (85%) 1H NMR (500MHz, Chloroform) δ 7.63 (s, 1H), 7.26 (s, 1H), 7.20 (s, 1H), 6.62 (s, 1H), 3.95 (s, 9H).
Embodiment 133
(Z)-2,4-dimethoxy-6-(2 – oxazole-2-base vinyl) methyl benzoate (12c)
Taking compound 11c as raw material, obtain compound 12c according to the method for embodiment 121, white solid (86%) 1H NMR (500MHz, CDCl3) δ 7.63 (s, 1H), 7.20 (s, 1H), 6.84 (m, 1H), 6.74 (d, J=8.0Hz, 2H), 6.63 (s, 1H), 3.94 (s, 6H), 3.86 (s, 3H).
Embodiment 134
(Z)-2-hydroxyl-4-methoxyl group-6-(2-oxazole-2-base-vinyl)-methyl benzoate (13c)
Taking compound 12c as raw material, obtain compound 13c according to the similar method of embodiment 6, white solid (77%) 1H NMR (500MHz, CDCl3) δ 7.65 (s, 2H), 7.20 (d, J=14.5Hz, 1H), 7.05 (s, 1H), 6.65 (s, 2H), 6.53 (s, 2H), 3.95 (s, 3H), 3.85 (s, 3H).
Embodiment 135
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-methyl benzoate (14c)
Taking compound 13c as raw material, obtain compound 14c according to the method for embodiment 7, white solid (74%).1H?NMR(500MHz,CDCl3)δ7.63(s,1H),7.56(t,J＝14.5Hz,1H),7.21(d,J＝14.5Hz,2H),7.00(s,1H),6.65(s,1H),5.42(s,J＝7.5Hz,1H),3.97(s,3H),3.82(s,3H),3.60(s,J＝7.5Hz,2H),1.92(s,3H),1.80(s,3H).
Embodiment 136
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-phenylformic acid (15c)
Taking compound 14c as raw material, obtain compound 15c according to the method for embodiment 8, white solid (86%).1H?NMR(500MHz,CDCl3)δ7.66(s,1H),7.50(s,1H),7.22(s,1H),7.16(s,1H),7.02(s,1H),6.76(s,1H),5.41(s,1H),3.82(s,3H),3.64(s,2H),1.91(s,3H),1.83(s,3H).
Embodiment 137
(Z)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-(2-oxazole-2-base vinyl)-phenol (16c)
Taking compound 15c as raw material, obtain compound 16c according to the method for embodiment 9, white solid (97%).1H?NMR(500MHz,CDCl3)δ7.64(s,1H),7.21(m,1H),7.00(d,J＝15.0Hz,2H),6.55(s,1H),6.49(s,1H),5.79(s,1H),5.38(s,1H),3.82(s,3H),3.56(s,2H),1.91(s,3H),1.82(s,3H).
Embodiment 138
2,4-dimethoxy-6-pyrroles-2-ethyl-acetylene base-methyl benzoate (11d)
Obtain compound 11d taking 6d as raw material according to the method for embodiment 120, white solid (82%) 1H NMR (500MHz, Chloroform) δ 7.46 (s, 1H), 6.93 (s, 1H), 6.78 (d, J=16.8Hz, 2H), 6.62 (s, 1H), 6.16 (s, 1H), 4.01 (s, 3H), 3.87 (d, J=7.0Hz, 6H).
Embodiment 139
(Z)-2,4-dimethoxy-6-(2 – pyrroles-2-base vinyl) methyl benzoate (12d)
Taking compound 11b as raw material, obtain compound 12d according to the method for embodiment 121, white solid (75%) 1H NMR (500MHz, CDCl3) δ 9.63 (s, 1H), 7.00 (t, J=16.0Hz, 1H), 6.92 (d, J=16.0Hz, 2H), 6.72 (s, 1H), 6.62 (s, 1H), 6.50 (s, 1H), 6.11 (s, 1H), 3.96 (s, 6H), 3.86 (s, 3H).
Embodiment 140
(Z)-2-hydroxyl-4-methoxyl group-6-(2-pyrroles-2-base-vinyl)-methyl benzoate (13d)
Taking compound 12d as raw material, obtain compound 13d according to the similar method of example 6, white solid (90%) 1H NMR (500MHz, CDCl3) δ 9.63 (s, 1H), 7.00 (d, J=15.5Hz, 2H), 6.93 (s, 1H), 6.63 (s, 1H), 6.50 (s, 1H), 6.11 (s, 1H), 3.97 (s, 3H), 3.85 (s, 3H).
Embodiment 141
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-methyl benzoate (14d)
Taking compound 13d as raw material, obtain compound 14d according to the method for embodiment 7, white solid (59%).1H?NMR(500MHz,CDCl3)δ9.68(s,1H),9.04(s,1H),7.10–6.98(m,3H),6.67(s,1H),6.51(s,1H),6.12(s,1H),5.48(t,J＝7.5Hz,1H),3.99(s,3H),3.81(s,3H),3.56(s,J＝7.5Hz,2H),1.94(s,3H),1.83(s,3H).
Embodiment 142
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-phenylformic acid (15d)
Taking compound 14d as raw material, obtain compound 15d according to the method for embodiment 8, white solid (79%) 1HNMR (500MHz, CDCl3) δ 9.65 (s, 3H), 8.40 (s, 3H), 7.10 (s, 7H), 6.96 (s, 1H), 6.76 (s, 3H), 6.51 (s, 3H), 6.12 (s, 3H), 5.54 (t, J=7.5Hz, 1H), 3.83 (s, 3H), 3.59 (d, J=7.5Hz, 2H), 1.90 (s, 8H), 1.81 (s, 8H).
Embodiment 143
(Z)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-[2-(1H-pyrroles-2-yl)-vinyl]-phenol (16d)
Taking compound 15d as raw material, obtain compound 16d according to the method for embodiment 9, white solid (87%).1H?NMR(500MHz,CDCl3)δ9.64(s,1H),7.08(s,1H),7.01(s,1H),6.84(s,1H),6.50(t,J＝8.5Hz,3H),6.12(s,1H),5.79(s,1H),5.38(t,J＝6.0Hz,1H),3.82(s,3H),3.55(d,J＝6.0Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 144
2-biphenyl-4-ethyl-acetylene base-4-2,6-dimethoxy-methyl benzoate (11e)
Obtain compound 11e taking 6e as raw material according to the method for embodiment 120, white solid (77%) 1H NMR (500MHz, Chloroform) δ 7.78 – 7.74 (m, 4H), 7.74 – 7.59 (m, 2H), 7.53 – 7.45 (m, 3H), 7.41 (s, 1H), 6.76 (s, 1H), 4.00 (s, 3H), 3.87 (s, 6H).
Embodiment 145
(Z)-2-(2-biphenyl-4-base-vinyl)-4,6-dimethoxy p-methyl (12e)
Taking compound 11e as raw material, obtain compound 12e according to the method for embodiment 121, white solid (91%) 1H NMR (500MHz, CDCl3) δ 7.77 (d, J=1.5Hz, 1H), 7.77 – 7.62 (m, 5H), 7.62 – 7.53 (m, 2H), 7.52 – 7.46 (m, 2H), 7.41 (s, 1H), 6.76 (s, 1H), 3.99 (s, 3H), 3.94 (s, 3H), 3.79 (s, 3H).
Embodiment 146
(Z)-2-(2-biphenyl-4-base-vinyl)-6-hydroxyl-4-methoxyl group-methyl benzoate (13e)
Taking compound 13d as raw material, obtain compound 13e according to the similar method of embodiment 6, white solid (82%) 1H NMR (500MHz, CDCl3) δ 7.64 – 7.57 (m, 2H), 7.57 – 7.44 (m, 5H), 7.00 (s, 1H), 6.81 (s, 1H), 6.68 (s, 1H), 6.50 (s, 1H), 3.97 (s, 3H), 3.83 (s, 3H).
Embodiment 147
(Z)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (14e)
Taking compound 13e as raw material, obtain compound 14e according to the method for embodiment 7, white solid (57%).1H?NMR(500MHz,CDCl3)δ9.04(s,1H),7.81–7.68(m,3H),7.68–7.58(m,3H),7.52–7.46(m,2H),7.42(s,1H),7.15(s,1H),7.08(d,J＝12.0Hz,2H),6.85(s,1H),5.42(t,J＝7.0Hz,1H),3.99(s,3H),3.76(s,3H),3.68(d,J＝7.0Hz,2H),1.92(s,3H),1.83(s,3H).
Embodiment 148
(Z)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (15e)
Taking compound 14e as raw material, obtain compound 15e according to the method for embodiment 8, white solid (88%) 1HNMR (500MHz, CDCl3) δ 7.78 – 7.74 (m, 2H), 7.69-7.45 (m, 4H), 7.40 (s, 1H), 6.90 (m, 2H), 6.79 (s, 1H), 5.41 (s, 1H), 3.80 (s, 3H), 3.57 (s, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 149
(Z)-5-(2-biphenyl-4-base-vinyl)-3-methoxyl group-2-(3-methyl but-2-ene base)-phenol (16e)
Taking compound 15e as raw material, obtain compound 16e according to the method for embodiment 9, white solid (80%).1H?NMR(500MHz,CDCl3)δ7.77(d,J＝1.5Hz,1H),7.77–7.61(m,3H),7.61–7.52(m,2H),7.52–7.46(m,2H),7.41(s,1H),6.73(d,J＝9.0Hz,2H),6.54(d,J＝9.0Hz,2H),5.83(s,1H),5.55(t,J＝7.0Hz,1H),3.76(s,3H),3.52(d,J＝7.0Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 150
2,4-dimethoxy-6-furans-2-ethyl-acetylene base-methyl benzoate (11f)
Obtain compound 11f taking 6f as raw material according to the method for embodiment 120, white solid (91%) 1H NMR (500MHz, Chloroform) δ 7.58 (s, 1H), 7.43 (s, 1H), 6.83 (s, 1H), 6.73 (s, 1H), 6.39 (s, 1H), 3.98 – 3.88 (m, 9H).
Embodiment 151
(Z)-2,4-dimethoxy-6-(2 – furans-2-base vinyl) methyl benzoate (12f)
Taking compound 11f as raw material, obtain compound 12f according to the method for embodiment 121.(87％)1H?NMR(500MHz,CDCl3)δ7.57(s,1H),6.86–6.72(m,3H),6.66(s,1H),6.61(s,1H),6.44(s,1H),4.00(s,3H),3.94(s,3H),3.86(s,3H).
Embodiment 152
(Z)-2-hydroxyl-4-methoxyl group-6-(2-pyrroles-2-base-vinyl)-methyl benzoate (13f)
Taking compound 12f as raw material, obtain compound 13f, white solid (91%) according to the similar method of embodiment 6.1H?NMR(500MHz,CDCl3)δ7.61(s,1H),7.14(s,1H),6.86(s,1H),6.65(d,J＝1.2Hz,2H),6.52(s,1H),6.44(s,1H),3.98(s,3H),3.85(s,3H).
Embodiment 153
(Z)-6-(2-furans-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (14f)
Taking compound 13f as raw material, obtain compound 14f according to the method for embodiment 7, white solid (63%).1H?NMR(500MHz,CDCl3)δ9.04(s,1H),7.63(s,1H),7.04(s,1H),6.85(d,J＝13.8Hz,2H),6.67(s,1H),6.44(s,1H),5.48(t,J＝6.0Hz,1H),3.98(s,3H),3.81(s,3H),3.56(d,J＝6.0Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 154
(Z)-6-(2-furans-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (15f)
Taking compound 14f as raw material, obtain compound 15f according to the method for embodiment 8, white solid (80%) 1HNMR (500MHz, CDCl3) δ 8.32 (s, 1H), 7.63 (s, 1H), 7.00 (m, 1H), 6.84 (d, J=12.0Hz, 2H), 6.76 (s, 1H), 6.44 (s, 1H), 5.54 (t, J=7.0Hz, 1H), 3.83 (s, 3H), 3.57 (d, J=7.0Hz, 2H), 1.90 (s, 3H), 1.81 (s, 3H).
Embodiment 155
(Z)-5-(2-furans-2-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol (16f)
Taking compound 15f as raw material, obtain compound 16f according to the method for embodiment 9, white solid (86%).1H?NMR(500MHz,CDCl3)δ7.63(s,1H),6.95–6.73(m,3H),6.49(s,1H),6.44(d,J＝6.5Hz,2H),5.81(s,1H),5.51(t,J＝7.0Hz,1H),3.82(s,3H),3.53(d,J＝7.0Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 156
2-(3,4-dihydroxyl-phenylene-ethynylene)-4,6-dimethoxy p-methyl (11g)
Obtain compound 11g taking 6g as raw material according to the similar method of embodiment 120, white solid (87%) 1HNMR (500MHz, Chloroform) δ 7.31 (d, J=4.0Hz, 2H), 6.92 (s, 1H), 6.62 (s, 1H), 6.57 (s, 1H), 5.62 (s, 1H), 5.54 (s, 1H), 3.98 – 3.90 (m, 9H).
Embodiment 157
(Z)-2-[2-(3,4-dihydroxyl-phenyl)-vinyl]-4,6-dimethoxy p-methyl (12g)
Taking compound 11g as raw material, obtain compound 12g according to the method for embodiment 121, white solid (75%) 1H NMR (500MHz, CDCl3) δ 7.06 (d, J=13.5Hz, 2H), 6.90 (s, 1H), 6.88 – 6.79 (m, 3H), 6.31 (s, 1H), 5.66 (s, 1H), 5.47 (s, 1H), 3.97 (s, 6H), 3.84 (s, 3H).
Embodiment 158
(Z)-2-[2-(3,4-dihydroxyl-phenyl)-vinyl]-6-hydroxyl-4-methoxyl group-methyl benzoate (13g)
Taking compound 12g as raw material, obtain compound 13g (95%) .1H NMR (500MHz, CDCl3) δ 7.07 (d, J=10.0Hz according to the method for embodiment 6,2H), 6.96 – 6.79 (m, 3H), 6.65 (s, 1H), 6.48 (s, 1H), 5.60 (s, 1H), 5.48 (s, 1H), 3.97 (s, 3H), 3.77 (s, 3H).
Embodiment 159
(Z)-6-[2-(3,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (14g)
Taking compound 13g as raw material, obtain compound 14g according to the method for embodiment 7, white solid (53%).1H?NMR(500MHz,CDCl3)δ7.86(s,1H),7.14(s,1H),7.05(s,1H),6.85(t,J＝4.5Hz,3H),6.58(s,1H),5.49(s,1H),5.42(m,2H),3.96(s,3H),3.72(s,3H),2.94(s,J＝6.0Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 160
(Z)-6-[2-(3,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (15g)
Taking compound 14g as raw material, obtain compound 15g according to the method for embodiment 8, white solid (82%) 1HNMR (500MHz, CDCl3) δ 9.70 (s, 1H), 7.70 (s, 1H), 7.10 (s, 1H), 6.86 (d, J=4.7Hz, 2H), 6.83 – 6.69 (m, 3H), 5.74 (s, 1H), 5.60 (s, 1H), 5.55 (s, J=7.0Hz, 1H), 3.84 (s, 3H), 3.55 (s, J=7.0Hz, 2H), 1.88 (s, 3H), 1.80 (s, 3H).
Embodiment 161
(Z)-4-{2-[3-hydroxy-5-methyl oxygen base-4-(3-methyl but-2-ene base)-phenyl]-vinyl }-benzene-1,2-glycol (16g)
Taking compound 15g as raw material, obtain compound 16g, white solid (76%) according to the similar method of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.13(s,1H),7.01(s,1H),6.84(s,1H),6.76–6.52(m,3H),6.54(s,1H),6.52(d,J＝12.5Hz,2H),5.82(s,1H),5.54(t,J＝6.0Hz,1H),5.47(s,1H),5.43(s,1H),3.74(s,3H),3.50(d,J＝6.0Hz,2H),1.90(s,3H),1.81(s,3H).
Embodiment 162
2-(2,4-dihydroxyl-phenylene-ethynylene)-4,6-dimethoxy p-methyl (11h)
Obtain compound 11h with 6h raw material according to the similar method of embodiment 120, white solid (87%) 1HNMR (500MHz, Chloroform) δ 7.39 (d, J=7.5Hz, 2H), 7.22 (s, 1H), 6.56 (s, 1H), 6.35 (d, J=13.3Hz, 2H), 6.03 (s, 1H), 3.98 – 3.90 (m, 9H).
Embodiment 163
(Z)-2-[2-(2,4-dihydroxyl-phenyl)-vinyl]-4,6-dimethoxy p-methyl (12h)
Taking compound 11h as raw material, obtain compound 12h according to the method for embodiment 121, white solid (78%).1H?NMR(500MHz,CDCl3)δ7.63(s,1H),6.87(d,J＝10.0Hz,2H),6.80(s,1H),6.33–6.23(m,3H),6.18(s,1H),5.67(s,1H),3.99(s,6H),3.89(s,3H).
Embodiment 164
(Z)-2-[2-(2,4-dihydroxyl-phenyl)-vinyl]-6-hydroxyl-4-methoxyl group-methyl benzoate (13h).
Taking compound 12h as raw material, obtain compound 13h (85%) according to the method for embodiment 6.1H?NMR(500MHz,CDCl3)δ7.58(s,1H),6.91(s,1H),6.84(s,1H),6.63(s,1H),6.49(s,1H),6.31(d,J＝11.5Hz,2H),6.19(s,1H),5.66(s,1H),3.97(s,3H),3.76(s,3H).
Embodiment 165
(Z)--6-[2-(2,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-methyl benzoate (14h)
Taking compound 13h as raw material, obtain compound 14h according to the method for embodiment 7, white solid (51%).1H?NMR(500MHz,CDCl3)δ7.86(s,1H),7.65(s,1H),6.88(d,J＝7.5Hz,2H),6.58(s,1H),6.32(d,J＝7.5Hz,2H),6.20(s,1H),5.67(s,1H),5.42(t,J＝7.0Hz,1H),3.96(s,3H),3.72(s,3H),2.93(d,J＝7.0Hz,2H),1.94(s,3H),1.80(s,3H).
Embodiment 166
(Z)-6-[2-(2,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-phenylformic acid (15h)
Taking compound 14h as raw material, obtain compound 15h according to the method for embodiment 8, white solid (86%) 1HNMR (500MHz, CDCl3) δ 7.70 (s, 1H), 7.46 (s, 1H), 6.86 (m, 2H), 6.80 (s, 1H), 6.26 (d, J=16.0Hz, 2H), 6.15 (s, 1H), 5.74 (s, J=7.5Hz, 1H), 5.61 (s, 1H), 3.84 (s, 3H), 3.55 (s, J=7.5Hz2H), 1.89 (s, 3H), (1.80 s, 3H).
Embodiment 167
(Z)-4-{2-[3-hydroxy-5-methyl oxygen base-4-(3-methyl but-2-ene base)-phenyl]-vinyl }-benzene-1,3-glycol (16h)
Taking compound 15h as raw material, obtain compound 16h, white solid (93%) according to the similar method of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.66(d,J＝7.5Hz,1H),6.78(s,1H),6.71(d,J＝12.5Hz,2H),6.54(s,1H),6.44(s,1H),6.31(d,J＝16.5Hz,2H),6.17(s,1H),5.84(s,2H),5.39(t,J＝7.0Hz,1H),3.69(s,3H),3.50(d,J＝7.0Hz2H),1.90(s,3H),1.81(s,3H).
Embodiment 168
Propanedioic acid is two-(2,4,6-trichlorophenyl) ester (17)
1,3-propanedioic acid (40g, 0.38mol) is dissolved in 1000mlDMF, under room temperature, add 2,4,6-Trichlorophenol (151g, 0.76mol), finish, drip phosphorus oxychloride (116.5g in this temperature, 0.76mol), ensure strictly anhydrously, finish, at 120 DEG C of reaction 7-8h, after reaction finishes, DMF is steamed, acetic acid ethyl dissolution system, saturated common salt washing, anhydrous magnesium sulfate drying spends the night.Filter, revolve to steam and remove ethyl acetate, residuum sherwood oil: ethyl acetate=8:1 crosses silicagel column, obtain compound (17) (122g, 64%) white solid 1H NMR (500MHz, CDCl3) δ 7.43 – 7.39 (m, 4H), 3.61 (s, 2H).
Embodiment 169
4-hydroxy-2-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate methyl ester (18)
Compound 17 (100g, 0.22mol) is dissolved in dry toluene, adds 3-amino-but-2-ene acid methyl esters (30g, 0.25mol) under room temperature, and the system that is warming up to refluxes, and after 2.5h, reaction finishes.Dry toluene is steamed, acetic acid ethyl dissolution system, saturated common salt washing, anhydrous magnesium sulfate drying spends the night.Filter, revolve to steam and remove ethyl acetate, residuum sherwood oil: ethyl acetate=10:1 crosses silicagel column, obtains compound 18 (25g, 64.1%) white solid.1H?NMR(500MHz,CDCl3)δ5.28(s,1H),3.82(s,3H),2.47(s,3H).
Embodiment 170
4,6-dimethoxy-2-methylnicotinic acid methyl esters (19)
Compound 18 (22g, 0.12mol) is dissolved in 400ml dry DMF, adds Anhydrous potassium carbonate (76g, 0.55mol), dropwise adds methyl iodide (37.5g, 0.26mol), finishes, and is warming up to 100 DEG C, keeps 3h, and reaction finishes.Dry DMF is steamed, acetic acid ethyl dissolution system, saturated common salt washing, anhydrous magnesium sulfate drying spends the night.Filter, revolve to steam and remove ethyl acetate, residuum sherwood oil: ethyl acetate=10:1 crosses silicagel column, obtains compound 19 (20g, 79%) white solid.1H?NMR(500MHz,CDCl3)δ6.42(s,1H),3.96(s,6H),3.88(s,3H),2.60(s,3H).
Embodiment 171
2-brooethyl-4,6-dimethoxy-nicotinic acid methyl ester (20)
Taking compound 19 as raw material, obtain compound 20 according to the method for embodiment 3, white solid (57%) 1HNMR (500MHz, CDCl3) δ 6.56 (s, 1H), 5.04 (s, 2H), 3.97 (s, 3H), 3.89 (m, 6H).
Embodiment 172
2-diethyl phosphite methyl-4,6-dimethoxy nicotinic acid methyl ester (21)
Taking compound 20 as raw material, obtain compound 21 according to the method for embodiment 4, white solid (65%), white solid 1H NMR (500MHz, CDCl3) δ 6.55 (s, 1H), 4.22 – 4.18 (m, 3H), 3.96 (s, 3H), 3.89 (s, 6H), 3.38 (s, 2H), 1.42 – 1.38 (m, 6H).
Embodiment 173
(E)-4,6-dimethoxy-2-styryl nicotinic acid methyl ester (22a)
Taking phenyl aldehyde and compound 21 as raw material, obtain this compound (22a) with the similar method of embodiment 5, white solid (87%) .1H NMR (500MHz, CDCl3) δ 7.62 (s, 1H), 7.62 – 7.47 (m, 3H), 7.42 – 7.36 (m, 2H), 7.31 (s, 1H), 6.45 (s, 1H), 3.99 – 3.88 (m, 9H).
Embodiment 174
(E)-4-hydroxyl-6-methoxyl group-2-styryl nicotinic acid methyl ester (23a)
Taking compound 22a as raw material, obtain compound 23a, white solid (92%) by the method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ7.52(t,J＝6.0Hz,1H),7.59–7.27(m,5H),6.27(s,1H),3.91(s,6H).
Embodiment 175
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-styryl-nicotinic acid methyl ester (24a)
Taking compound 23a as raw material, obtain compound 24a, white solid (53%) by the method reaction of embodiment 7.1H?NMR(500MHz,CDCl3)δ7.68(s,1H),7.56–7.49(m,2H),7.47(s,1H),7.41–7.35(m,2H),7.30(s,1H),7.16(s,1H),5.22(s,J＝7.0Hz,1H),4.08(s,3H),3.95(s,3H),3.52(s,J＝7.0Hz,2H),1.97(s,3H),1.85(s,3H).
Embodiment 176
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-styryl-nicotinic acid (25a)
Taking compound 24a as raw material, obtain compound 25a, white solid (89%) by the method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ7.62(dd,J＝12.5,6.0Hz,4H),7.58–7.51(m,2H),7.59–7.55(m,2H),7.49(s,1H),7.42–7.36(m,2H),7.31(s,1H),5.21(t,J＝7.0Hz1H),4.08(s,3H),3.54(d,J＝7.0Hz,2H),1.90(s,3H),1.83(s,3H).
Embodiment 177
(E)-2-methoxyl group-3-(3-methyl but-2-ene base)-6-styryl-pyridine-4-alcohol (26a)
Taking compound 25a as raw material, obtain compound 26a, white solid (93%) by the method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.54(t,J＝5.0Hz,2H),7.42–7.36(m,2H),7.30(d,J＝18.0Hz,2H),6.02(s,1H),5.89(s,1H),5.26(s,J＝7.0Hz,1H),4.06(s,3H),3.50(s,J＝7.0Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 178
(E)-4,6-dimethoxy-2-(2-pyridine-2-base-vinyl)-nicotinic acid methyl ester (22b)
Taking 2-pyridylaldehyde and compound 21 as raw material, obtain this compound 22b with the similar method of embodiment 5, white solid (78%) 1H NMR (500MHz, CDCl3) δ 8.42 (s, 1H), 7.86 (t, J=6.0Hz, 1H), 7.41 (s, 1H), 7.36 (d, 1H), 7.31 (d, J=6.0Hz, 2H), 6.45 (s, 1H), 3.97 (s, 3H), 3.91 (s, 6H).
Embodiment 179
(E)-4-hydroxyl-6-methoxyl group-2-(2-pyridine-2-base-vinyl)-nicotinic acid methyl ester (23b)
Taking compound 22b as raw material, obtain compound 23b, white solid (92%) by the method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ8.46(s,1H),7.78(s,1H),7.71(s,1H),7.42(d,J＝7.5Hz,2H),7.33(s,1H),6.29(s,1H),3.97(s,3H),3.89(s,3H).
Embodiment 180
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridine-2-base-vinyl)-nicotinic acid methyl ester (24b)
Taking compound 23b as raw material, obtain compound 24b, white solid (53%) by the method reaction of embodiment 7.1H?NMR(500MHz,CDCl3)δ8.54(s,1H),8.46-8.22(m,2H),7.77(t,J＝18.5Hz,1H),7.42(d,J＝18.5Hz,2H),7.33(s,1H),5.24(t,J＝7.5Hz,1H),4.07(s,3H),3.98(s,3H),3.45(d,J＝7.5Hz2H),1.90(s,3H),1.81(s,3H).
Embodiment 181
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridine-2-base-vinyl)-nicotinic acid (25b)
Taking compound 24b as raw material, obtain compound 25b, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.42(s,1H),7.76(s,1H),7.43–7.29(m,5H),5.21(t,J＝7.5Hz,1H),4.05(s,3H),3.38(d,J＝7.5Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 182
(E)-2-methoxyl group-3-(3-methyl but-2-ene base)-6-(2-pyridine-2-base-vinyl)-pyridine-4-alcohol (26b)
Taking compound 25b as raw material, obtain compound 26b, white solid (87%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ8.46(s,1H),7.75(d,J＝16.0Hz,2H),7.47–7.38(m,2H),7.33(s,1H),6.06(s,1H),5.90(s,1H),5.26(t,J＝7.5Hz,1H),4.05(s,3H),3.42(d,J＝7.5Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 183
(E)-4,6-dimethoxy-2-(2-pyridin-3-yl-vinyl)-nicotinic acid methyl ester (22c)
Taking 3-pyridylaldehyde and compound 21 as raw material, obtain this compound with the similar method of embodiment 5, white solid (82%) 1H NMR (500MHz, CDCl3) δ 8.52 (d, J=4.2Hz, 2H), 7.82 (s, 1H), 7.54 (s, 1H), 7.37 (s, 1H), 7.28 (s, 1H), 6.46 (s, 1H), 3.95 (s, 6H), 3.89 (s, 3H).
Embodiment 184
(E)-4-hydroxyl-6-methoxyl group-2-(2-pyridin-3-yl-vinyl)-nicotinic acid methyl ester (23c)
Taking compound 22c as raw material, obtain compound 23c, white solid (90%) by the similar method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ8.61(s,1H),8.51(s,1H),7.76(s,1H),7.47(s,1H),7.37(s,1H),7.29(s,1H),6.27(s,1H),3.93(s,3H),3.89(s,3H).
Embodiment 185
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridin-3-yl-vinyl)-nicotinic acid methyl ester (24c)
Taking compound 23c as raw material, obtain compound 24c, white solid (53%) by the similar method reaction of embodiment 7.1H?NMR(500MHz,CDCl3)δ8.54–8.49(m,2H),8.07(s,1H),7.80(s,1H),7.44(s,1H),7.37(s,1H),7.31(s,1H),5.45(s,J＝7.5Hz,1H),4.07(s,3H),4.02(s,3H),3.30(s,J＝7.5Hz,2H),1.90(s,3H),1.81(s,3H).
Embodiment 186
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridin-3-yl-vinyl)-nicotinic acid (25c)
Taking compound 24c as raw material, obtain compound 25c, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.51(d,J＝8.0Hz,2H),7.76(s,1H),7.68–7.32(m,3H),6.96(d,J＝8.0Hz,1H),5.22(t,J＝7.5Hz,1H),4.05(s,3H),3.38(d,J＝7.5Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 187
(E)-2-methoxyl group-3-(3-methyl but-2-ene base)-6-(2-pyridin-3-yl-vinyl)-pyridine-4-alcohol (26c)
Taking compound 25c as raw material, obtain compound 26c, white solid (96%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ8.59(s,1H),8.55(d,J＝8.0Hz,1H),7.79(s,1H),7.46(d,J＝8.0Hz,2H),7.24(s,1H),6.01(s,1H),5.89(s,1H),5.25(t,J＝7.5Hz,1H),4.06(s,3H),3.42(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 188
(E)-4,6-dimethoxy-2-(2-pyridin-4-yl-vinyl)-nicotinic acid methyl ester (22d)
Taking 4-pyridylaldehyde and compound 21 as raw material, obtain this compound 22d with the similar similar method of embodiment 5, white solid (82%) 1H NMR (500MHz, CDCl3) δ 8.65 – 8.50 (m, 2H), 7.53 (d, J=12.3Hz, 2H), 7.44 – 7.29 (m, 2H), 6.46 (s, 1H), 3.95 (s, 6H), 3.89 (s, 3H).
Embodiment 189
(E)-4-hydroxyl-6-methoxyl group-2-(2-pyridin-3-yl-vinyl)-nicotinic acid methyl ester (23d)
Taking compound 22d as raw material, obtain compound 23d, white solid (90%) by the similar method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ8.65–8.51(m,4H),7.79(s,3H),7.60(s,1H),7.45–7.30(m,4H),6.28(s,2H),3.97(s,6H),3.89(s,6H).
Embodiment 190
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridin-4-yl-vinyl)-nicotinic acid methyl ester (24d)
Taking compound 23d as raw material, obtain compound 24d, white solid (44%) by the similar method reaction of embodiment 7.1H?NMR(500MHz,CDCl3)δ8.64–8.50(m,2H),7.50(d,J＝9.0Hz,2H),7.42–7.31(m,2H),7.14(s,1H),5.30(t,J＝7.5Hz,1H),4.04(s,3H),3.90(s,3H),3.34(d,J＝7.5Hz2H),1.91(s,3H),1.82(s,3H).
Embodiment 191
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridin-4-yl-vinyl)-nicotinic acid (25d)
Taking compound 24d as raw material, obtain compound 25d, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.61–8.49(m,2H),7.53(s,1H),7.36–7.26(m,3H),7.21(s,1H),5.22(t,J＝7.5Hz,1H),4.05(s,3H),3.39(d,J＝7.5Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 192
(E)-2-methoxyl group-3-(3-methyl but-2-ene base)-6-(2-pyridin-3-yl-vinyl)-pyridine-4-alcohol (26d)
Taking compound 25d as raw material, obtain compound 26d, white solid (90%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ8.64–8.49(m,2H),7.53(s,1H),7.36–7.26(m,3H),7.21(s,1H),5.22(t,J＝7.5Hz,1H),4.05(s,3H),3.39(d,J＝7.5Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 193
(E)-2-(2-furans-2-base-vinyl)-4,6-dimethoxy-nicotinic acid methyl ester (22e)
Taking 2 furan carboxyaldehyde and compound 21 as raw material, obtain this compound 22e with the similar method of embodiment 5, white solid (78%) 1H NMR (500MHz, CDCl3) δ 7.63 (t, J=10.0Hz, 1H), 7.31 (d, J=10.0Hz, 2H), 6.82 (s, 1H), 6.50 (s, 1H), 6.44 (s, 1H), 3.95 (s, 6H), 3.90 (s, 3H).
Embodiment 194
(E)-2-(2-furans-2-base-vinyl)-4-hydroxyl-6-methoxyl group nicotinic acid methyl ester (23e)
Taking compound 22e as raw material, obtain compound 23e, white solid (53%) 1H NMR (500MHz, CDCl3) δ 7.66 (s by the similar method reaction of embodiment 7,1H), 7.49 (s, 1H), 7.45 (s, 1H), 6.84 (s, 1H), 6.45 (s, 1H), 6.31 (s, 1H), 3.99 (s, 3H), 3.90 (s, 3H).
Embodiment 195
(E)-2-(2-furans-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid methyl ester (24e)
Taking compound 23e as raw material, obtain compound 24e, white solid (53%) 1H NMR (500MHz by the similar method reaction of embodiment, CDCl3) δ 7.62 (s, 1H), 7.43 (s, 1H), 7.35 (d, J=9.0Hz1H), 7.09 (s, 1H), 6.81 (d, J=9.0Hz, 1H), 6.43 (s, 1H), 5.26 (t, J=7.5Hz, 1H), 4.07 (s, 3H), 3.98 (s, 3H), 3.45 (d, J=7.5Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 196
(E)-2-(2-furans-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid
(25e)
Taking compound 24e as raw material, obtain compound 25e, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ7.68(s,3H),7.50-7.45(m,3H),7.41(s,1H),6.85(s,3H),6.46(s,2H),5.23(s,2H),4.09(s,2H),3.52(s,2H),1.91(s,3H),1.83(s,7H).
Embodiment 197
(E)-6-(2-furans-2-base-vinyl)-2-methoxyl group-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol (26e)
Taking compound 25e as raw material, obtain compound 26e, white solid (93%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.64(s,1H),7.30-7.16(m,3H),6.82(s,1H),6.44(s,1H),6.05(s,1H),5.90(s,1H),5.24(t,J＝7.0Hz,1H),4.06(s,3H),3.42(d,J＝7.0Hz,2H),1.92(s,3H),1.87(s,3H).
Embodiment 198
(E)-4,6-dimethoxy-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid methyl ester (22f)
Taking 2-pyrrole aldehyde and compound 21 as raw material, obtain this compound 22f with the similar method of embodiment 5, white solid (78%) 1H NMR (500MHz, CDCl3) δ 9.64 (s, 1H), 7.53-7.38 (m, 2H), 7.12 (s, 1H), 7.03 (s, 1H), 6.51 (d, J=10.5Hz, 2H), 6.12 (s, 1H), 3.99 – 3.89 (m, 9H).
Embodiment 199
(E)-4-hydroxyl-6-methoxyl group-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid methyl ester (23f)
Taking compound 22f as raw material, obtain compound 23f, white solid (53%) 1H NMR (500MHz by the similar method reaction of embodiment 7, CDCl3) δ 9.65 (s, 1H), 7.65 (s, 1H), (7.45-7.33 t, J=7.5Hz, 1H), 7.13 (s, 1H), 6.58 (s, 1H), 6.31 (s, 1H), 6.12 (d, J=10.5Hz1H), 3.97 (s, 3H), 3.90 (s, 3H).
Embodiment 200
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid methyl ester (24f)
Taking compound 23f as raw material, obtain compound 24f, white solid (72%) 1H NMR (500MHz by the similar method reaction of embodiment, CDCl3) δ 9.71 (s, 1H), 7.46-7.34 (m, 2H), 7.00 (d, J=11.5Hz, 2H), 6.45 (s, 1H), 6.09 (s, 1H), 5.23 (t, J=7.5Hz, 1H), 4.09 (s, 3H), 3.96 (s, 3H), (3.46 d, J=7.5Hz, 2H), 1.90 (s, 3H), 1.82 (s, 3H).
Embodiment 201
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid (25f)
Taking compound 24f as raw material, obtain compound 25f, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ9.66(s,1H),7.59(s,1H),7.50(d,J＝10.0Hz,2H),7.16(s,1H),6.58(s,1H),6.14(s,1H),5.23(s,1H),4.10(s,3H),3.52(s,J＝7.5Hz,2H),1.92(s,3H),1.83(s,3H).
Embodiment 202
(E)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-pyridine-4-alcohol (26f)
Taking compound 25f as raw material, obtain compound 26f, white solid (93%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ9.66(s,1H),7.56(d,J＝15.5Hz,1H),7.23(s,1H),7.18(d,J＝15.5Hz,2H),6.53(s,1H),6.13(s,1H),6.07(s,1H),5.87(s,1H),5.21(t,J＝7.5Hz,1H),4.09(s,3H),3.48(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 203
(E)-4,6-dimethoxy-2-(2-thiazol-2-yl-vinyl) nicotinic acid methyl ester (22g)
Taking 2-thiazole carboxaldehyde and compound 21 as raw material, obtain this compound 22g with the similar method of embodiment 5, white solid (78%) 1H NMR (500MHz, CDCl3) δ 7.84-7.79 (m, 1H), 7.78 (d, J=12.0Hz, 2H), 7.46 (d, J=5.7Hz, 2H), 6.51 (s, 1H), 3.99 – 3.88 (m, 9H).
Embodiment 204
(E)-4-hydroxyl-6-methoxyl group-2-(2-thiazol-2-yl-vinyl)-nicotinic acid methyl ester (23g)
Taking compound 22g as raw material, obtain compound 23g, white solid (53%) 1H NMR (500MHz by the similar method reaction of embodiment 6, CDCl3) δ 7.80 (d, J=54.5Hz, 2H), 7.53 (d, J=71.8Hz, 2H), 6.33 (s, 1H), 3.97 (s, 3H), 3.90 (s, 3H).
Embodiment 205
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-thiazol-2-yl-vinyl-nicotinic acid methyl ester (24g)
Taking compound 23g as raw material, obtain compound 24g, white solid (53%) 1H NMR (500MHz by the similar method reaction of embodiment 7, CDCl3) δ 7.79 (s, 1H), 7.74 (s, 1H), 7.55-7.43 (m, 2H), 7.21 (s, 1H), 5.26 (t, J=7.5Hz, 1H), 4.07 (s, 3H), 3.99 (s, 3H), 3.46 (d, J=7.5Hz, 2H), 1.91 (s, 3H), 1.83 (s, 3H).
Embodiment 206
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-thiazol-2-yl-vinyl-nicotinic acid (25g)
Taking compound 24g as raw material, obtain compound 25g, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ7.87(s,1H),7.75(s,1H),7.49-7.40(m,1H),7.22-7.10(m,2H),5.26(t,J＝7.5Hz,1H),4.10(s,3H),3.52(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 207
(E)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-pyridine-4-alcohol (26g)
Taking compound 25g as raw material, obtain compound 26g, white solid (93%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.85(s,1H),7.75(s,1H),7.49-7.23(m,2H),6.09(s,1H),5.92(s,1H),5.28(s,1H),4.07(s,3H),3.46(s,2H),1.91(s,3H),1.82(s,3H).
Embodiment 208
(E)-2-[2-(1H-imidazoles-2-yl)-vinyl]-4,6-dimethoxy-nicotinic acid methyl ester (22h)
Taking 2-imidazole formaldehyde and compound 21 as raw material, obtain this compound 22h with the similar method of embodiment 5, white solid (78%) 1H NMR (500MHz, CDCl3) δ 7.70 (s, 1H), 7.65 (s, 1H), 7.11 (t, J=9.5Hz, 2H), 6.49 (t, J=9.5Hz, 2H), 3.99 (s, 3H), 3.92 (s, 6H).
Embodiment 209
(E)-4-hydroxyl-2-[2-(1H-imidazoles-2-yl) vinyl]-6-methoxyl group nicotinic acid methyl ester (23h)
Taking compound 22h as raw material, obtain compound 23h, white solid (53%) 1H NMR (500MHz, CDCl3) δ 7.78 (s by the similar method reaction of embodiment 7,1H), 7.65 (s, 1H), 7.50 (s, 1H), 7.19 (s, 1H), 6.49 (s, 1H), 6.32 (s, 1H), 3.97 (s, 3H), 3.90 (s, 3H).
Embodiment 210
(E)-4-hydroxyl-2-[2-(1H-imidazoles-2-yl)-vinyl]-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid methyl ester (24h)
Taking compound 23h as raw material, obtain compound 24h, white solid (53%) 1H NMR (500MHz by the similar method reaction of embodiment 8, CDCl3) δ 7.89 (s, 1H), 7.73 (s, 1H), 7.65 (s, 1H), 7.49 (s, 1H), 7.29 (s, 1H), 6.50 (s, 1H), 5.39 (s, 1H), 4.08 (s, 3H), 3.88 (s, 3H), 3.23 (d, J=7.5Hz2H), 1.90 (s, 3H), (1.81 s, 3H).
Embodiment 211
(E)-4-hydroxyl-2-[2-(1H-imidazoles-2-yl)-vinyl]-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid (25h)
Taking compound 24h as raw material, obtain compound 25h, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.24(s,1H),7.73(s,1H),7.65-7.44(m,2H),7.14(s,1H),6.50(s,1H),5.31(t,J＝7.5Hz,1H),4.08(s,3H),3.49(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 212
(E)-6-[2-(1H-imidazoles-2-yl)-vinyl]-2-methoxyl group-3-(3-methyl but-2-ene base)-pyridine-4-alcohol (26h)
Taking compound 25h as raw material, obtain compound 26h, white solid (72%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.71(s,1H),7.65(s,1H),7.32-7.13(m,2H),6.50(s,1H),6.09(s,1H),5.86(s,1H),5.21(t,J＝7.5Hz,1H),4.09(s,3H),3.48(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 213
(E)-4,6-dimethoxy-2-[2-(5-methoxypyridine-2-yl)-vinyl]-nicotinic acid methyl ester (22i)
Taking 5-methoxypyridine-2-formaldehyde and compound 21 as raw material, obtain this compound 22i with the similar method of embodiment 5, white solid (87%) 1H NMR (500MHz, CDCl3) δ 8.04 (s, 2H), 7.73 (s, 2H), 7.37 (d, J=7.5Hz, 2H), 7.12 (s, 1H), 6.44 (s, 2H), 3.91 (s, 3H).
Embodiment 214
(E)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-yl)-vinyl]-nicotinic acid methyl ester (23i)
Taking compound 22i as raw material, obtain compound 23i, white solid (71%) 1H NMR (500MHz by the similar method reaction of embodiment 7, CDCl3) δ 8.06 (s, 1H), 7.74 (d, J=16.0Hz, 2H), 7.49 (s, 1H), 7.13 (s, 1H), 6.26 (s, 1H), 3.97 (s, 3H), 3.89 (s, 6H).
Embodiment 215
(E)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-yl) vinyl]-5-(3-methyl but-2-ene base) nicotinic acid methyl ester
Taking compound 23i as raw material, obtain compound 24i, white solid (64%) 1H NMR (500MHz by the similar method reaction of embodiment 8, CDCl3) δ 8.04 (s, 1H), 7.77-7.66 (m, 1H), 7.48 (d, J=5.5Hz, 2H), 7.42 (s, 1H), 7.12 (s, 1H), 5.19 (t, J=7.5Hz, 1H), 4.08 (s, 3H), 3.98 (s, 3H), 3.87 (s, 3H), 3.44 (d, J=7.5Hz, 2H), 1.90 (s, 3H), 1.81 (s, 3H).
Embodiment 216
(E)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-yl) vinyl]-5-(3-methyl but-2-ene base) nicotinic acid
Taking compound 24i as raw material, obtain compound 25i, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.02(d,J＝16.0Hz,2H),7.79-7.64(m,1H),7.54(s,1H),7.43(s,1H),7.14(s,1H),5.26(t,J＝7.5Hz,1H),4.06(s,3H),3.87(s,3H),3.44(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 217
(E)-2-methoxyl group-6-[2-(5-methoxypyridine-2-yl)-vinyl]-3-(3-methyl but-2-ene base)-pyridine-4-alcohol
Taking compound 25i as raw material, obtain compound 26i, white solid (93%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ8.12(s,1H),7.82–7.41(m,3H),7.53(d,J＝8.0Hz,1H),7.53(d,J＝8.0Hz,1H),7.13(s,1H),6.02(s,1H),5.89(s,1H),5.25(t,J＝7.5Hz,1H),4.05(s,3H),3.88(s,3H),3.41(d,J＝7.5Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 218
(22 ' a) for 4,6-dimethoxy-2-phenylene-ethynylene-nicotinic acid methyl ester
Obtain compound 21 ' a (77%) 1H NMR (500MHz, Chloroform) δ 7.71 – 7.59 (m, 2H) taking 22a as raw material according to the method for embodiment 120,7.45 (s, 1H), 7.40 – 7.35 (m, 2H), 6.59 (s, 1H), 3.96 (s, 6H), 3.89 (s, 3H).
Embodiment 219
(Z)-4,6-dimethoxy-2-styryl nicotinic acid methyl ester (27a)
Taking compound 22 ' a as raw material, obtain compound 27a, white solid (80%) 1H NMR (500MHz, CDCl3) δ 7.54 – 7.41 (m by the method reaction of embodiment 121,2H), 7.40 – 7.35 (m, 2H), 7.30 (s, 1H), 6.84 (s, 1H), 6.64 (s, 1H), 6.50 (s, 1H), 4.00 (s, 3H), 3.85 (s, 6H).
Embodiment 220
(Z)-4-hydroxyl-6-methoxyl group-2-styryl nicotinic acid methyl ester (28a)
Taking compound 27a as raw material, obtain compound 28a (91%) by the method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ7.53–7.41(m,2H),7.40–7.34(m,2H),7.30(s,1H),6.94(d,J＝45.0Hz,2H),6.28(s,1H),3.96(s,3H),3.85(s,3H).
Embodiment 221
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-styryl-nicotinic acid methyl ester (29a)
Taking compound 28a as raw material, obtain compound 29a, white solid (53%) by the method reaction of embodiment 7.1H?NMR(500MHz,CDCl3)δ7.59–7.46(m,2H),7.42–7.36(m,2H),7.31(s,1H),7.18(s,1H),7.11(s,1H),6.84(s,1H),5.23(s,1H),4.08(s,3H),3.95(s,3H),3.55(s,2H),1.90(s,3H),1.82(s,3H).
Embodiment 222
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-styryl-nicotinic acid (30a)
Taking compound 29a as raw material, obtain compound 30a, white solid (89%) by the method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ7.81(s,1H),7.61–7.49(m,2H),7.42–7.37(m,2H),7.31(s,1H),7.19(s,1H),7.04(s,1H),5.36(t,J＝7.5Hz,1H),4.09(s,3H),3.53(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 223
(Z)-2-methoxyl group-3-(3-methyl but-2-ene base)-6-styryl-pyridine-4-alcohol (31a)
Taking compound 30a as raw material, obtain compound 31a, white solid (87%) by the method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.60–7.48(m,3H),7.42–7.36(m,3H),7.32(s,1H),7.16(s,1H),7.04(s,2H),6.03(s,2H),5.85(s,2H),5.20(t,J＝7.5Hz,1H),4.08(s,3H),3.52(s,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 224
(22 ' b) for 4,6-dimethoxy-2-pyridine-2-ethyl-acetylene base-nicotinic acid methyl ester
Obtain compound 21 ' b (87%) 1H NMR (500MHz, Chloroform) δ 8.04 (s, 1H) taking 22b as raw material according to the method for embodiment 120,7.53 (s, 1H), 7.31 (s, 1H), 7.04 (s, 1H), 6.52 (s, 1H), 4.02 (s, 3H), 3.91 (s, 6H).
Embodiment 225
(Z)-4,6-dimethoxy-2-(2-pyridine-2-base-vinyl)-nicotinic acid methyl ester (27b)
Taking 22 ' b as raw material, obtain this compound 27b with the similar method of embodiment 121, white solid (78%) 1H NMR (500MHz, CDCl3) δ 8.45 (s, 1H), 7.41 (d, J=8.5Hz, 2H), 7.33 (s, 1H), 7.25 (s, 1H), 7.06 (s, 1H), 6.47 (s, 1H), 3.97 (s, 3H), 3.91 (s, 6H).
Embodiment 226
(Z)-4-hydroxyl-6-methoxyl group-2-(2-pyridine-2-base-vinyl)-nicotinic acid methyl ester (28b)
Taking compound 27b as raw material, obtain compound 28b, white solid (92%) by the method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ8.43(s,1H),7.40-7.15(m,2H),7.31(d,J＝10.5Hz,2H),7.12(d,J＝1.5Hz,1H),6.28(s,1H),3.96(s,3H),3.86(s,3H).
Embodiment 227
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridine-2-base-vinyl)-nicotinic acid methyl ester (29b)
Taking compound 28b as raw material, obtain compound 29b, white solid (46%) by the method reaction of embodiment 7.1H?NMR(500MHz,CDCl3)δ8.80(s,1H),8.37(dd,J＝7.5,1.5Hz,2H),7.43(s,1H),7.32(s,2H),7.32–7.29(m,1H),7.12(s,1H),6.99(s,2H),5.30(t,J＝7.0Hz,1H),3.96(s,3H),3.40(d,J＝7.0Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 228
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridine-2-base-vinyl)-nicotinic acid (30b)
Taking compound 29b as raw material, obtain compound 305b, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.37(dd,J＝7.5,1.5Hz,1H),7.81(s,1H),7.42(s,2H),7.30-7.00(m,2H),6.96(s,2H),5.26(s,3H),4.03(s,3H),3.39(s,2H),1.90(s,3H),1.82(s,3H).
Embodiment 229
(Z)-2-methoxyl group-3-(3-methyl but-2-ene base)-6-(2-pyridine-2-base-vinyl)-pyridine-4-alcohol (31b)
Taking compound 25b as raw material, obtain compound 26b, white solid (91%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ8.44(s,1H),7.41(d,J＝12.5Hz,2H),7.33-7.00(m,2H),6.98(s,1H),6.04(s,1H),5.89(s,1H),5.27(t,J＝7.5Hz,1H),4.05(s,3H),3.42(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 230
(22 ' c) for 4,6-dimethoxy-2-pyridin-3-yl ethynyl-nicotinic acid methyl ester
Obtain compound 22 ' c (78%) 1H NMR (500MHz, Chloroform) δ 8.04 (s, 1H) taking 22c as raw material according to the method for embodiment 120,7.53 (s, 1H), 7.31 (s, 1H), 7.04 (s, 1H), 6.52 (s, 1H), 4.02 (s, 3H), 3.91 (d, J=17.6Hz, 6H).
Embodiment 231
(Z)-4,6-dimethoxy-2-(2-pyridin-3-yl-vinyl)-nicotinic acid methyl ester (27c)
Taking 22 ' c as raw material, obtain this compound with the similar method of embodiment 121, white solid (82%) 1HNMR (500MHz, CDCl3) δ 8.49 (s, 2H), 7.73 (dt, J=7.5,1.5Hz, 1H), 7.36-7.11 (m, 1H), 6.79 (dd, J=7.5,4.0Hz, 2H), 6.71 – 6.62 (m, 1H), 6.45 (s, 1H), 3.99 (s, 3H), 3.92 (s, 3H), (3.86 s, 3H).
Embodiment 232
(Z)-4-hydroxyl-6-methoxyl group-2-(2-pyridin-3-yl-vinyl)-nicotinic acid methyl ester (28c)
Taking compound 27c as raw material, obtain compound 28c, white solid (88%) by the similar method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ8.51(s,1H),8.28(s,1H),7.78(s,1H),7.37(s,1H),7.00(s,1H),6.86(s,1H),6.28(s,1H),3.96(s,3H),3.86(s,3H).
Embodiment 233
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridin-3-yl-vinyl)-nicotinic acid methyl ester (29c)
Taking compound 28c as raw material, obtain compound 29c, white solid (67%) by the similar method reaction of embodiment 7.1H?NMR(500MHz,CDCl3)δ8.57–8.49(m,3H),7.73(s,1H),7.35(s,1H),6.88(d,J＝14.0Hz,2H),5.30(t,J＝7.5Hz,1H),3.96(s,6H),3.39(d,J＝7.5Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 234
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridin-3-yl-vinyl)-nicotinic acid (30c)
Taking compound 29c as raw material, obtain compound 30c, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.52(s,1H),8.34(s,1H),7.77(s,1H),7.42(s,1H),7.38(s,1H),6.83(s,1H),6.66(s,1H),5.32(t,J＝7.5Hz,1H),3.99(s,3H),3.42(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 235
(Z)-2-methoxyl group-3-(3-methyl but-2-ene base)-6-(2-pyridin-3-yl-vinyl)-pyridine-4-alcohol (31c)
Taking compound 30c as raw material, obtain compound 31c, white solid (90%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ8.58-8.42(m,2H),7.79(s,1H),7.38(s,1H),7.14(s,1H),7.00(s,1H),6.03(s,1H),5.86(s,1H),5.20(t,J＝7.0Hz,1H),4.07(s,3H),3.44(d,J＝7.0Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 236
(22 ' d) for 4,6-dimethoxy-2-pyridin-4-yl ethynyl-nicotinic acid methyl ester
Obtain compound 22 ' d (77%) 1H NMR (500MHz taking 22d as raw material according to the method for embodiment 120, CDCl3) δ 8.40 – 8.25 (m, 2H), 7.52 – 7.38 (m, 2H), 6.64 (s, 1H), 3.96 (s, 6H), (3.89 s, 3H).
Embodiment 237
(Z)-4,6-dimethoxy-2-(2-pyridin-4-yl-vinyl)-nicotinic acid methyl ester (27d)
Taking 22 ' d as raw material, obtain this compound 27d with the similar similar method of embodiment 121, white solid (82%) 1H NMR (500MHz, CDCl3) δ 8.65 – 8.49 (m, 2H), 7.37 – 7.23 (m, 2H), 6.82 (d, J=8.0Hz, 2H), 6.51 (s, 1H), 3.99 (s, 3H), 3.86 (s, 6H).
Embodiment 238
(Z)-4-hydroxyl-6-methoxyl group-2-(2-pyridin-3-yl-vinyl)-nicotinic acid methyl ester (28d)
Taking compound 27d as raw material, obtain compound 28d, white solid (92%) by the similar method reaction of embodiment 6.1H?NMR(500MHz,CDCl3)δ8.64–8.50(m,2H),7.38–7.23(m,2H),7.10(s,1H),6.89(s,1H),6.27(s,1H),3.96(s,3H),3.85(s,3H).
Embodiment 239
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridin-4-yl-vinyl)-nicotinic acid methyl ester (29d)
Taking compound 28d as raw material, obtain compound 29d, white solid (92%) by the similar method reaction of embodiment 7.1H?NMR(500MHz,CDCl3)δ8.66–8.56(m,2H),8.54(s,1H),7.36–7.21(m,2H),7.11(s,1H),6.77(s,1H),5.34(s,J＝7.5Hz,1H),4.06(s,3H),3.92(s,3H),3.46(s,J＝7.5Hz,2H),1.91(s,3H),1.83(s,3H).
Embodiment 240
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-pyridin-4-yl-vinyl)-nicotinic acid (30d)
Taking compound 29d as raw material, obtain compound 30d, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.69–8.54(m,2H),7.75(s,1H),7.42–7.28(m,2H),7.18(d,J＝17.5Hz,2H),5.36(t,J＝7.5Hz,1H),4.08(s,3H),3.45(d,J＝7.5Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 241
(Z)-2-methoxyl group-3-(3-methyl but-2-ene base)-6-(2-pyridin-3-yl-vinyl)-pyridine-4-alcohol (31d)
Taking compound 30d as raw material, obtain compound 31d, white solid (91%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ8.63–8.49(m,3H),7.37–7.23(m,3H),6.96(s,2H),6.02(s,1H),5.95(s,1H),5.19(t,J＝7.5Hz,1H),3.94(s,3H),3.36(s,J＝7.5Hz,2H),1.90(s,3H),1.81(s,3H
Embodiment 242
2-furans-2-ethyl-acetylene base-4-2, (22 ' e) for 6-dimethoxy-nicotinic acid methyl ester
Obtain compound 22 ' e (86%) 1H NMR (500MHz, Chloroform) δ 7.64 (s, 1H) taking 22e as raw material according to the method for embodiment 120,7.07 (s, 1H), 6.57 (s, 1H), 6.42 (s, 1H), 3.96 (d, J=10.1Hz, 6H), 3.90 (s, 3H).
Embodiment 243
(Z)-2-(2-furans-2-base-vinyl)-4,6-dimethoxy-nicotinic acid methyl ester (27e)
Taking 22 ' e as raw material, obtain this compound 27e with the similar method of embodiment 121, white solid (78%) 1H NMR (500MHz, CDCl3) δ 7.65 (s, 1H), 7.06 (s, 1H), 6.83 (d, J=2.5Hz, 2H), 6.51 (s, 1H), 6.44 (s, 1H), 3.99 – 3.85 (m, 9H).
Embodiment 244
(Z)-2-(2-furans-2-base-vinyl)-4-hydroxyl-6-methoxyl group nicotinic acid methyl ester (28e)
Taking compound 27e as raw material, obtain compound 28e, white solid (77%) 1H NMR (500MHz, CDCl3) δ 7.49 (s by the similar method reaction of embodiment 7,1H), 6.94 (s, 1H), 6.77 (s, 1H), 6.71 (s, 1H), 6.38 (s, 1H), 6.32 (s, 1H), 3.96 (s, 3H), 3.90 (s, 3H).
Embodiment 245
(Z)-2-(2-furans-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid methyl ester (29e)
Taking compound 28e as raw material, obtain compound 29e, white solid (49%) 1H NMR (500MHz by the similar method reaction of embodiment, CDCl3) δ 8.54 (s, 1H), 7.67-7.60 (m, 1H), 7.06 (d, J=6.0Hz, 2H), 6.87 (s, 1H), 6.45 (s, 1H), 5.26 (t, J=7.5Hz, 1H), 4.08 (s, 3H), 3.98 (s, 3H), 3.49 (s, J=7.5Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 246
(Z)-2-(2-furans-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid (30e)
Taking compound 29e as raw material, obtain compound 30e, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.88(s,1H),7.67-7.33(m,2H),7.04(s,1H),6.92(s,1H),6.46(s,1H),5.31(t,J＝7.5Hz,1H),4.08(s,3H),3.53(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 247
(Z)-6-(2-furans-2-base-vinyl)-2-methoxyl group-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol (31e)
Taking compound 30e as raw material, obtain compound 31e, white solid (93%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.66(s,1H),7.02-6.85(m,3H),6.45(s,1H),6.05(s,1H),5.88(s,1H),5.38(t,J＝7.5Hz,1H),4.09(s,3H),3.45(d,J＝7.5Hz,2H),1.90(s,3H),1.82(s,3H).
Embodiment 248
2-pyrroles-2-ethyl-acetylene base-4-2, (22 ' f) for 6-dimethoxy-nicotinic acid methyl ester
Obtain compound 22 ' f (85%) 1H NMR (500MHz, Chloroform) δ 7.04 (s, 1H) taking 22f as raw material according to the method for embodiment 120,6.83 (s, 1H), 6.68 (s, 1H), 6.60 (s, 1H), 6.18 (s, 1H), 4.01 (s, 3H), 3.90 (s, 3H), 3.86 (s, 3H).
Embodiment 249
(Z)-4,6-dimethoxy-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid methyl ester (27f)
Taking 22 ' f as raw material, obtain this compound 27f with the similar method of embodiment 121, white solid (78%) 1H NMR (500MHz, CDCl3) δ 9.64 (s, 1H), 7.18-7.02 (m, 2H), 6.78 (s, 1H), 6.51 (d, J=5.5Hz, 2H), 6.12 (s, 1H), 3.99 – 3.89 (m, 9H).
Embodiment 250
(Z)-4-hydroxyl-6-methoxyl group-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid methyl ester (28f)
Taking compound 27f as raw material, obtain compound 28f, white solid (87%) 1H NMR (500MHz, CDCl3) δ 9.64 (s by the similar method reaction of embodiment 7,1H), 7.24-7.13 (m, 2H), 6.79 (s, 1H), 6.51 (s, 1H), 6.31 (s, 1H), 6.12 (s, 1H), 3.98 (s, 3H), 3.91 (s, 3H).
Embodiment 251
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid methyl ester (29f)
Taking compound 28f as raw material, obtain compound 29f, white solid (59%) 1H NMR (500MHz by the similar method reaction of embodiment, CDCl3) δ 9.64 (s, 1H), 7.25 (d, J=1.5Hz, 2H), 7.13-6.81 (m, 2H), 6.51 (s, 1H), 6.12 (s, 1H), 5.26 (s, 1H), 4.10 (s, 3H), 3.96 (s, 3H), 3.51 (s, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 252
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid (30f)
Taking compound 29f as raw material, obtain compound 30f, white solid (87%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ9.65(s,1H),7.27-7.14(m,3H),6.81(s,1H),6.51(s,1H),6.12(s,1H),5.27(s,J＝7.5Hz,1H),4.10(s,3H),3.52(s,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 253
(Z)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-pyridine-4-alcohol (31f)
Taking compound 30f as raw material, obtain compound 31f, white solid (96%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ9.66(s,1H),7.27-7.15(m,2H),6.98(s,1H),6.53(s,1H),6.13(s,1H),6.07(s,1H),5.87(s,1H),5.21(t,J＝7.5Hz,1H),4.09(s,3H),3.48(d,J＝7.5Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 254
(22 ' g) for 4,6-dimethoxy-2-thiazol-2-yl ethynyl-nicotinic acid methyl ester
Obtain compound 22 ' g (75%) 1H NMR (500MHz taking 22g as raw material according to the method for embodiment 120, Chloroform) δ 7.59 (s, 1H), 7.41 (s, 1H), 6.58 (s, 1H), 3.97 (s, 6H), 3.90 (s, 3H).
Embodiment 255
(Z)-4,6-dimethoxy-2-(2-thiazol-2-yl-vinyl) nicotinic acid methyl ester (27g)
Taking 22 ' g as raw material, obtain this compound 22g with the similar method of embodiment 121, white solid (78%) 1H NMR (500MHz, CDCl3) δ 7.75 (s, 1H), 7.45 (s, 1H), 7.00 (s, 2H), 6.88 (s, 1H), 6.53 (s, 1H), 3.95 (s, 6H), 3.90 (s, 3H).
Embodiment 256
(Z)-4-hydroxyl-6-methoxyl group-2-(2-thiazol-2-yl-vinyl)-nicotinic acid methyl ester (28g)
Taking compound 27g as raw material, obtain compound 28g, white solid (86%) 1H NMR (500MHz, CDCl3) δ 7.75 (d by the similar method reaction of embodiment 6, J=7.5Hz, 1H), 7.56 (dd, J=15.0Hz, 7.5Hz, 2H), 7.49 – 7.43 (m, 1H), 7.26 (s, 1H), 6.34 (s, 1H), 3.98 (s, 3H), 3.91 (s, 3H).
Embodiment 257
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-thiazol-2-yl-vinyl)-nicotinic acid methyl ester (29g)
Taking compound 28g as raw material, obtain compound 29g, white solid (53%) 1H NMR (500MHz by the similar method reaction of embodiment 7, CDCl3) δ 8.54 (s, 1H), 7.75 (s, 1H), 7.55-7.25 (m, 2H), 5.27 (t, J=7.0Hz, 1H), 4.08 (s, 3H), 3.98 (s, 3H), 3.50 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 258
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-2-(2-thiazol-2-yl-vinyl)-nicotinic acid (30g)
Taking compound 30g as raw material, obtain compound 30g, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.54(s,1H),7.75-7.46(m,2H),7.14(d,J＝8.5Hz,2H),5.30(t,J＝7.0Hz,1H),4.07(s,3H),3.52(d,J＝7.0Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 259
(E)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-pyridine-4-alcohol (31g)
Taking compound 30g as raw material, obtain compound 31g, white solid (95%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.74(s,1H),7.45(s,1H),7.05(s,1H),6.82(s,1H),6.05(s,1H),5.90(s,1H),5.23(t,J＝7.0Hz,1H),4.02(s,3H),3.41(d,J＝7.0Hz,2H),1.90(s,3H),1.81(s,3H).
Embodiment 260
2-(1H-imidazoles-2-ethyl-acetylene base)-4, (22 ' h) for 6-dimethoxy-nicotinic acid methyl ester
Obtain compound 21 ' h. (76%) 1H NMR (500MHz, Chloroform) δ 7.20 (s, 1H) taking 22h as raw material according to the method for embodiment 120,7.10 (s, 1H), 6.80 (s, 1H), 6.57 (s, 1H), 3.97 (s, 6H), 3.90 (s, 3H).
Embodiment 261
(Z)-2-[2-(1H-imidazoles-2-yl)-vinyl]-4,6-dimethoxy-nicotinic acid methyl ester (27h)
Taking 22 ' h as raw material, obtain this compound 27h with the similar method of embodiment 121, white solid (78%) 1H NMR (500MHz, CDCl3) δ 7.72 (s, 1H), 7.23-7.07 (m, 1H), 6.74 (s, 1H), 6.69 (s, 1H), 6.50 (d, J=3.5Hz, 2H), 3.99 (s, 3H), 3.93 (s, 6H).
Embodiment 262
(Z)-4-hydroxyl-2-[2-(1H-imidazoles-2-yl) vinyl]-6-methoxyl group nicotinic acid methyl ester (28h)
Taking compound 27h as raw material, obtain compound 23h, white solid (78%) 1H NMR (500MHz, CDCl3) δ 9.98 (s by the similar method reaction of embodiment 7,1H), 7.65 (s, 1H), 7.40-7.09 (m, 2H), 7.11 (s, 1H), 6.86 (s, 1H), 6.50 (s, 1H), 6.31 (s, 1H), 3.98 (s, 3H), 3.93 (s, 3H).
Embodiment 263
(Z)-4-hydroxyl-2-[2-(1H-imidazoles-2-yl)-vinyl]-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid methyl ester (29h)
Taking compound 28h as raw material, obtain compound 29h, white solid (53%) 1H NMR (500MHz by the similar method reaction of embodiment 8, CDCl3) δ 7.65 (s, 1H), 7.41 (s, 1H), 7.26 (s, 1H), 7.11 (s, 1H), 6.86 (s, 1H), 6.50 (s, 1H), 5.25 (t, J=7.0Hz, 1H), 4.09 (s, 3H), 3.97 (s, 3H), 3.51 (d, J=7.0Hz, 2H), 1.91 (s, 3H), 1.82 (s, 3H).
Embodiment 264
(Z)-4-hydroxyl-2-[2-(1H-imidazoles-2-yl)-vinyl]-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid (30h)
Taking compound 29h as raw material, obtain compound 30h, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.25(s,1H),7.65(s,1H),7.44-7.19(m,2H),7.14(s,1H),6.50(s,1H),5.26(t,J＝7.0Hz,1H),4.08(s,3H),3.50(d,J＝7.0Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 265
(Z)-6-[2-(1H-imidazoles-2-yl)-vinyl]-2-methoxyl group-3-(3-methyl but-2-ene base)-pyridine-4-alcohol (31h)
Taking compound 30h as raw material, obtain compound 31h, white solid (96%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.65(s,1H),7.42-7.12(m,2H),7.08(s,1H),6.50(s,1H),6.09(s,1H),5.86(s,1H),5.21(t,J＝7.0Hz,1H),4.09(s,3H),3.48(d,J＝7.0Hz,2H),1.91(s,3H),1.82(s,3H).
Embodiment 266
2-(5-ethylpyridine-2-ethyl-acetylene base)-4, (22 ' i) for 6-dimethoxy-nicotinic acid methyl ester
Obtain compound 21 ' i (79%) 1H NMR (500MHz, Chloroform) δ 8.19 (s, 1H) taking 22i as raw material according to the method for embodiment 120,7.38 (s, 2H), 6.51 (s, 1H), 3.92 (s, 12H).
Embodiment 267
(Z)-4,6-dimethoxy-2-[2-(5-methoxypyridine-2-yl)-vinyl]-nicotinic acid methyl ester (27i)
Taking 22 ' i as raw material, obtain this compound 27i with the similar method of embodiment 121, white solid (78%) 1H NMR (500MHz, CDCl3) δ 8.03 (s, 2H), 7.40 (s, 2H), 7.11 (s, 2H), 7.03 (s, 1H), 6.75 (s, 1H), 6.51 (s, 1H), 3.99 (s, 3H), 3.86 (s, 6H).
Embodiment 268
(Z)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-yl)-vinyl]-nicotinic acid methyl ester (28i)
Taking compound 22i as raw material, obtain compound 28i, white solid (79%) 1H NMR (500MHz by the similar method reaction of embodiment 7, CDCl3) δ 8.05 (s, 1H), 7.39 (s, 1H), 7.10 (d, J=6.5Hz, 2H), 7.03 (s, 1H), 6.27 (s, 1H), 3.96 (s, 3H), 3.87 (s, 6H).
Embodiment 269
(Z)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-yl) vinyl]-5-(3-methyl but-2-ene base) nicotinic acid methyl ester (29i)
Taking compound 28i as raw material, obtain compound 29i, white solid (58%) 1H NMR (500MHz by the similar method reaction of embodiment 8, CDCl3) δ 8.59 (s, 1H), 8.05 (s, 1H), 7.40 (s, 1H), 7.19 – 6.93 (m, 3H), 5.31 (t, J=7.0Hz, 1H), 3.97 (s, 6H), 3.87 (s, 3H), 3.40 (d, J=7.0Hz, 2H), 1.90 (s, 3H), 1.82 (s, 3H).
Embodiment 270
(Z)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-yl) vinyl]-5-(3-methyl but-2-ene base) nicotinic acid (30i)
Taking compound 29i as raw material, obtain compound 30i, white solid (89%) by the similar method reaction of embodiment 8.1H?NMR(500MHz,CDCl3)δ8.13(s,1H),7.54(s,1H),7.36(d,J＝17.2Hz,2H),7.16(d,J＝20.0Hz,2H),5.23(s,1H),4.08(s,3H),3.88(s,3H),3.49(s,2H),1.91(s,3H),1.82(s,3H).
Embodiment 271
(Z)-2-methoxyl group-6-[2-(5-methoxypyridine-2-yl)-vinyl]-3-(3-methyl but-2-ene base)-pyridine-4-alcohol (31i)
Taking compound 30i as raw material, obtain compound 31i, white solid (93%) by the similar method reaction of embodiment 9.1H?NMR(500MHz,CDCl3)δ7.96(s,1H),7.47(s,1H),7.13(s,1H),6.92(s,1H),6.86(s,1H),5.98(s,1H),5.86(s,1H),5.33(s,J＝7.0Hz,1H),3.96(s,3H),3.88(s,3H),3.36(s,J＝7.0Hz,2H),1.90(s,3H),1.81(s,3H).
Embodiment 272
2-carbonyl-4-hydroxyl-6-methyl cyclohexane-3-alkene methyl carbonate (32)
Sodium Metal 99.5 (3.1g, 0.134mol) be dissolved in anhydrous methanol (200ml), add methyl acetoacetate (12.0g in room temperature, 0.103mol), with methyl crotonate (12.4g, 0.124mol), add, back flow reaction 6h, reaction is finished, and steams most of methyl alcohol, residuum joins frozen water (200ml), be extracted with ethyl acetate (3X50ml), water layer regulates pH to be less than 2 with 15% dilute hydrochloric acid, then is extracted with ethyl acetate (3X50ml).Merge organic layer, organic layer is washed with saturated common salt, and anhydrous MgSO4 is dry.Filter, solvent evaporated, residuum obtains white solid (13.2g, 70%) with petrol ether/ethyl acetate recrystallization.1H?NMR(400MHz,DMSO-d6):11.37(s,1H),5.21(s,1H),3.63(s,3H),3.09(d,J＝9.2Hz,1H),2.32(m,3H),0.94(d,J＝6.0Hz,3H).
Embodiment 273
Bromo-6 methyl-toluates of 2,4-dihydroxyl-3-(33)
Compound 38 (10.0g, 0.054mol) is dissolved in glacial acetic acid (150ml), at room temperature drips acetic acid (40ml) solution of bromine (19.9g, 0.124mol), drips off, and at room temperature reacts 12h.Reaction is finished, and reaction solution is poured in frozen water, separates out a large amount of white solids, filter, and filter cake massive laundering, dry.Gained solid is further crossed silicagel column by petrol ether/ethyl acetate and is obtained compared with pure products, white solid (5.6g, 40%).1H?NMR(400MHz,DMSO-d6):11.72(s,1H),10.98(s,1H),6.41(s,1H),3.86(s,3H),2.21(s,3H).
Embodiment 274
Bromo-6 methyl-toluates of 2,4-dimethoxy-3-(34)
Taking compound 33 as raw material, obtain product according to the method for embodiment 2, white solid (95%).1H?NMR(400MHz,CDCl3):6.52(s,1H),3.91(s,3H),3.89(s,3H),3.86(s,3H),2.30(s,3H).
Embodiment 275
Bromo-6 bromomethyl-benzoic acid methyl esters of 2,4-dimethoxy-3-(35)
Taking compound 34 as raw material, obtain product according to the method for embodiment 3, white solid (82%).1H?NMR(400MHz,CDCl3):3.90(s,3H),3.94(s,3H),3.96(s,3H),4.53(s,2H),6.73(s,1H).
Embodiment 276
The bromo-6-diethyl phosphite of 2,4-dimethoxy-3-methyl-toluate (36)
Taking compound 35 as raw material, obtain product according to the method for embodiment 4, white solid (86%).1H?NMR(400MHz,CDCl3):3.90(s,3H),3.94(s,3H),3.96(s,3H),4.53(s,2H),6.73(s,1H).
Embodiment 277
6-(diethoxy phosphorous acid ester group)-2,4-dimethoxy-3-(3-methyl but-2-ene base amino) methyl benzoate (37a)
By compound 36 (5g, 0.012mol) be dissolved in dry toluene, add isopentene group amine, three (dibenzalacetone) two palladiums, potassium tert.-butoxide, be heated to 110 DEG C, keep temperature 16h, after reaction finishes, toluene is steamed, acetic acid ethyl dissolution (3X50ml), saturated aqueous common salt washed twice, water layer is extracted with ethyl acetate (3X50ml) again.Merge organic layer, anhydrous MgSO4 is dry.Filter, solvent evaporated, residuum obtains white solid (3.8g, 76%) with petrol ether/ethyl acetate recrystallization.1H?NMR(500MHz,CDCl3)δ6.62(s,1H),5.12(s,1H),4.51(m,1H),4.15(dd,J＝17.5,4.0Hz,6H),3.97(s,3H),3.92(s,3H),3.87(s,3H),2.93(s,2H),1.87(s,3H),1.79(s,3H),1.44–1.40(m,6H).
Embodiment 278
(E)-2,4-dimethoxy-3-(3-methyl but-2-ene base amino)-6-styryl-methyl benzoate (38a)
Taking compound 37a as raw material, obtain product according to the method for embodiment 5, white solid (81%).1H?NMR(500MHz,CDCl3)δ7.68–7.55(m,2H),7.46–7.40(m,2H),7.28(s,1H),7.14(s,1H),6.93(d,J＝2.5Hz,2H),5.33(s,1H),4.93(s,1H),4.16(d,J＝16.0Hz,2H),3.94(d,J＝16.0Hz,6H),3.87(s,3H),1.89(s,3H),1.80(s,3H).
Embodiment 279
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base amino)-6-styryl-methyl benzoate (39a)
Taking compound 38a as raw material, obtain product according to the method for embodiment 6, white solid (74%).1H?NMR(500MHz,CDCl3)δ7.66–7.54(m,2H),7.44–7.38(m,2H),7.27(d,J＝8.0Hz,2H),6.87(s,1H),6.55(s,1H),5.29(s,1H),4.83(s,1H),4.20(s,1H),4.10(s,1H),4.03(s,3H),3.90(s,3H),1.89(s,3H),1.80(s,3H).
Embodiment 280
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base amino)-6-styryl-phenylformic acid (40a)
Taking compound 39a as raw material, obtain product according to the method for embodiment 8, white solid (69%).1H?NMR(500MHz,CDCl3)δ7.71–7.59(m,2H),7.53(s,1H),7.46–7.40(m,2H),7.27(s,1H),6.95(s,1H),6.72(s,1H),5.45(s,1H),4.92(s,1H),4.16(d,J＝14.0Hz,2H),3.91(s,3H),1.89(s,3H),1.80(s,3H).
Embodiment 281
6-(diethoxy phosphorous acid ester group)-2,4-dimethoxy-3-(3-methyl-butyl amino) methyl benzoate (37b)
Taking isoamylamine as raw material, obtain product according to the method for embodiment 277, white solid (70%).1H?NMR(500MHz,CDCl3)δ6.64(s,1H),5.75(s,1H),4.20–4.16(m,3H),3.97(s,3H),3.92(s,3H),3.85(s,3H),3.49(s,1H),3.38(s,1H),2.93(s,2H),1.64(d,J＝15.0Hz,3H),1.44–1.40(m,6H),0.98(s,6H).
Embodiment 282
(E)-2,4-dimethoxy-3-(3-methyl-butyl amino)-6-styryl-methyl benzoate (38b)
Taking compound 37b as raw material, obtain product according to the method for embodiment 5, white solid (71%).1H?NMR(500MHz,CDCl3)δ7.70–7.57(m,3H),7.42-7.26(m,4H),6.98(s,1H),6.80(s,1H),5.64(s,1H),3.98(s,3H),3.92(s,3H),3.81(s,3H),3.46(s,2H),1.82(s,1H),1.65(s,1H),1.02(s,6H).
Embodiment 283
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-butyl amino)-6-styryl-methyl benzoate (39b)
Taking compound 38b as raw material, obtain product according to the method for embodiment 6, white solid (73%).1H?NMR(500MHz,CDCl3)δ7.68–7.56(m,2H),7.51–7.31(m,2H),7.34(dd,J＝18.5,13.5Hz,4H),6.96(s,1H),6.65(s,1H),3.94(s,6H),3.87(s,1H),3.41(t,J＝13.5Hz,2H),1.65(m,1H),1.00(s,d,J＝13.5Hz,6H).
Embodiment 284
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-butyl amino)-6-styryl-phenylformic acid (40b)
Taking compound 39b as raw material, obtain product according to the method for embodiment 8, white solid (84%).1H?NMR(500MHz,CDCl3)δ7.60(t,J＝12.0Hz,3H),7.45–7.39(m,2H),7.27(s,1H),6.97(s,1H),6.73(s,1H),5.49(s,1H),3.92(s,3H),3.50(s,1H),3.37(t,d,J＝8.0Hz,2H),1.69(m,2H),1.03(d,J＝8.0Hz,6H).
Embodiment 285
3-butoxy-6-(diethoxy phosphorous acid ester group)-2,4-dimethoxy p-methyl (37C)
Taking propyl carbinol as raw material, obtain product according to the method for embodiment 277, white solid (70%).1H?NMR(500MHz,CDCl3)δ6.64(s,1H),5.75(s,1H),4.20–4.16(m,3H),3.97(s,3H),3.92(s,3H),3.85(s,3H),3.49(s,1H),3.38(s,1H),2.93(s,2H),1.64(d,J＝15.0Hz,3H),1.44–1.40(m,6H),0.98(s,6H).
Embodiment 286
(E)-2,4-dimethoxy-3-(3-methyl-butyl amino)-6-styryl-methyl benzoate (38b)
Taking compound 37b as raw material, obtain product according to the method for embodiment 5, white solid (71%).1H?NMR(500MHz,CDCl3)δ7.70–7.57(m,3H),7.42-7.26(m,4H),6.98(s,1H),6.80(s,1H),5.64(s,1H),3.98(s,3H),3.92(s,3H),3.81(s,3H),3.46(s,2H),1.82(s,1H),1.65(s,1H),1.02(s,6H).
Embodiment 287
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-butyl amino)-6-styryl-methyl benzoate (39b)
Taking compound 38b as raw material, obtain product according to the method for embodiment 6, white solid (73%).1H?NMR(500MHz,CDCl3)δ7.68–7.56(m,2H),7.51–7.31(m,2H),7.34(dd,J＝18.5,13.5Hz,4H),6.96(s,1H),6.65(s,1H),3.94(s,6H),3.87(s,1H),3.41(t,J＝13.5Hz,2H),1.65(m,1H),1.00(s,d,J＝13.5Hz,6H).
Embodiment 288
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-butyl amino)-6-styryl-phenylformic acid (40b)
Taking compound 39b as raw material, obtain product according to the method for embodiment 8, white solid (84%).1H?NMR(500MHz,CDCl3)δ7.60(t,J＝12.0Hz,3H),7.45–7.39(m,2H),7.27(s,1H),6.97(s,1H),6.73(s,1H),5.49(s,1H),3.92(s,3H),3.50(s,1H),3.37(t,d,J＝8.0Hz,2H),1.69(m,2H),1.03(d,J＝8.0Hz,6H).
Experimental example 1 anti-influenza virus activity is measured
Mdck cell is inoculated 96 well culture plates, is placed in 5%CO 2, 37 C cultivate 24 hours.Mdck cell adds the about 100TCID50 of influenza virus (A/H1N1, A/H3N2 or B/13/79 type), and 37 DEG C of absorption hypsokinesis in 2 hours venom of preventing or cure a disease adds respectively the maintenance medium of different dilution the compounds of this invention or positive control drug ribavirin.Establish the virus control of not dosing and the contrast of the cell of virus-free infection simultaneously, 37 C cultivate the each group of cytopathy degree (CPE) (approximately 36 hours) of observing in the time that virus control group lesion degree (CPE) reaches 4+, calculate each sample resisiting influenza virus half-inhibition concentration (IC50), result is referring to table 1.
The anti-COxsackie of experimental example 2 (CoxaskiEs) virus activity is measured
VEro cell kind 96 well culture plates, 24 hours about 100TCID50 of postoperative infection virus (cells of coxsackie B 3 virus), adsorb 2 hours, abandon virus liquid, add the compounds of this invention sample that contains different concns and the maintenance medium of positive control drug ribavirin (RBV), establish the virus control of not dosing and the contrast of the cell of virus-free infection simultaneously, in the time that reaching 4+, observes virus control group lesion degree (CPE) each group of cytopathy degree (CPE), by REEd-MuEnch method, calculation sample is to viral half-inhibition concentration (IC50) respectively, and result is listed table 2 in.
Experimental example 3 anti AIDS virus (HIV) determination of activity
MT-4 cell infects after 1.5h with substratum washing 2 times with 37 DEG C of absorption of 100TCID50HIV-1 III B virus, is mixed with 2 × 10 with nutrient solution 5cell mL-1,100 μ L are inoculated in 96 porocyte culture plates, add respectively the liquid of different concns or the positive drug AZT liquid of 4 times of dilutions of 3 times of dilutions simultaneously, and each concentration repeats 2 holes, establishes cell control group.Put in 37 C, 5%CO2 and saturated humidity incubator and cultivate, after dosing 96h, suct 100 μ L clearly, with the content of kit measurement P24 antigen, calculate IC50.The activity of the anti-HIV of described compound is in table 2.
Experimental example 4 hepatitis B virus resisting (HBV) determination of activity
HepG2.2.15 Tissue Culture Flask covers with after cell, through digestion, is mixed with every milliliter of 200,000 cells, inoculation 96 well culture plates, and every hole 100ml, 37 DEG C of 5%CO2 cultivate 24 hours, and cell is tested after growing up to individual layer.Medicine is mixed with after different concns with nutrient solution, adds 96 porocyte culture plates, and 37 DEG C of 5%CO2 cultivate, and cell cultures to the is observed with inverted microscope for 3 days, taking cytopathy (CPE) as cytotoxicity index.Record cytopathy, destroying is completely 4; 75% is 3; 50% is 2; 25% is 1; Anosisly become 0.Press Reed-Muench method and calculate the poisonous concentration of half (TC50) and maximal non-toxic concentration (TC0).Plate inner cell extracts DNA in cell with a small amount of DNA rapid extraction test kit, add primer, by the level (HVB Ct value) of DNA and the level (GAPDH Ct value) of cell internal reference gene GAPDH in qPCR test kit and iQ5 quantitative PCR instrument detection by quantitative cell.Calculate inhibition percentage by following formula.((HBV Ct cell contrast-HBV Ct medicine group)/(GAPDH Ct cell contrast-GAPDH Ct medicine group) × 100%, with Reed-Muench method calculating (EC50) to suppress percentage %=1/2^.The selection result is listed in table 3
The anti-hepatitis C virus of experimental example 5 (HCV) determination of activity
Huh7.5 cell is with 3 × 10 4the density of cells/cm2 is inoculated in 96 orifice plates, cultivates after 24h, with 45IU/cell cells infected, adds liquid or solvent control processing with HCV virus supernatant liquor simultaneously.Cultivate after 72h, substratum is abandoned in suction, by total RNA in RNeasy Mini Kit extraction cell, one-step real-time RT-PCR kit detection by quantitative for HCV rna expression level, with calculating the inhibiting rate of medicine to HCV, and with the poisonous concentration EC50 of Reed-Muench method calculating half.The activity of the anti-HCV of described compound is in table 3.

Claims (9)

1. one group has compound or its pharmacy acceptable salt of structure as shown in general formula I,
R in formula 1represent H, carboxyl, replaces or unsubstituted alkoxyl formyl, replaces or unsubstituted carbamyl, replaces or unsubstituted sulfydryl;
R 2representation hydroxy, replaces or unsubstituted alkoxyl group, replaces or unsubstituted methanoyl, replace or unsubstituted amino or halogen, or isoureido;
R 3represent H, isopentene group, isopentyl, allyl group, halogen, amino, substituted-amino;
R 4representation hydroxy, replaces or unsubstituted alkoxyl group, replaces or unsubstituted methanoyl, replace or unsubstituted amino or halogen, or isoureido;
R 5represent H, replace or unsubstituted aryl, replace or unsubstituted heteroaryl, replace or unsubstituted alkyl;
R 6represent H, replace or unsubstituted aryl, replace or unsubstituted heteroaryl, replace or unsubstituted alkyl;
X represents C or N.
2. compound as claimed in claim 1 or its pharmacy acceptable salt, wherein,
R 1be selected from hydrogen, carboxyl, methoxycarbonyl;
R 2be selected from hydroxyl, methoxyl group;
R 3be selected from isopentene group, isopentyl, isopentene group amine, isoamylamine;
R 5be selected from 2-furans, 2-thiazole, 2-imidazoles, 4-biphenyl, 2-pyridine, 3-pyridine, 4-pyridine, 6-methoxyl group-2-pyridine, 2,4-dihydroxy-benzene, 3,4-dihydroxy-benzene;
R 6be selected from 2-pyrroles, 3-pyrroles, 2-methoxyl group-3-pyrroles, 2-furans, 3-furans, 2-methoxyl group-3-furans, 2-thiazole, 5-thiazole, 4-methoxyl group-5-thiazole, 2-imidazoles, 3-imidazoles, 2-oxazole, 2-methoxyl group-5-oxazole, 5-methoxyl group-3H-imidazoles, 4-biphenyl, 2-pyridine, 3-pyridine, 4-pyridine, 6-methoxyl group-2-pyridine, 2,4-dihydroxy-benzene, 3,4-dihydroxy-benzene;
R 7be selected from isopentene group, isopentyl.
3. compound as claimed in claim 1 or its pharmacy acceptable salt, it is:
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-phenylformic acid;
(E)-2-hydroxyl-6-[2-(1H-imidazoles-2-yl)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-2-hydroxyl-6-[2-(1H-imidazoles-2-yl)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-phenylformic acid;
(E)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-6-(2-furans-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-6-(2-furans-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-6-[2-(3,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-6-[2-(3,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-6-[2-(2,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-6-[2-(2,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(6-methoxypyridine-3-yl)-vinyl]-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(6-methoxypyridine-3-yl)-vinyl]-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-6-[2-(4,6-dimethoxy-pyridine-3-yl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-6-[2-(4,6-dimethoxy-pyridine-3-yl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxypyridine-4-yl)-vinyl]-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxypyridine-4-yl)-vinyl]-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-6-[2-(2,5-dimethoxy-pyridine-4-yl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-6-[2-(2,5-dimethoxy-pyridine-4-yl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-3-yl) vinyl] methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-3-yl) vinyl] phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-1H-pyrroles-3-yl)-vinyl]-3-(3-methyl-but-2-ene base-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-1H-pyrroles-3-yl)-vinyl]-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-6-(2-furans-3-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-6-(2-furans-3-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group furans-3-yl)-vinyl]-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group furans-3-yl)-vinyl]-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-2-hydroxyl-6-[2-(2H-imidazol-4 yl)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-2-hydroxyl-6-[2-(2H-imidazol-4 yl)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-2H-imidazol-4 yl)-vinyl]-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-2H-imidazol-4 yl)-vinyl]-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazole-5-base-vinyl)-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazole-5-base-vinyl)-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group-thiazole-5-yl)-vinyl]-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group-thiazole-5-yl)-vinyl]-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-5-base-vinyl)-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-5-base-vinyl)-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxyl group-oxazole-5-yl)-vinyl]-3-(3-methyl-but-2-ene base)-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxyl group-oxazole-5-yl)-vinyl]-3-(3-methyl-but-2-ene base)-phenylformic acid;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-styryl-nicotinic acid methyl ester;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-styryl-nicotinic acid;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridine-2-base-vinyl)-nicotinic acid methyl ester;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridine-2-base-vinyl)-nicotinic acid;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridin-3-yl-vinyl)-nicotinic acid methyl ester;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridin-3-yl-vinyl)-nicotinic acid;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridin-4-yl-vinyl)-nicotinic acid methyl ester;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridin-4-yl-vinyl)-nicotinic acid;
(E)-2-(2-furans-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-nicotinic acid methyl ester;
(E)-2-(2-furans-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-nicotinic acid;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid methyl ester;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-thiazol-2-yl-vinyl-nicotinic acid methyl ester;
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-thiazol-2-yl-vinyl-nicotinic acid;
(E)-4-hydroxyl-2-[2-(1H-imidazoles-2-yl)-vinyl]-6-methoxyl group-5-(3-methyl-but-2-ene base)-nicotinic acid methyl ester;
(E)-4-hydroxyl-2-[2-(1H-imidazoles-2-yl)-vinyl]-6-methoxyl group-5-(3-methyl-but-2-ene base)-nicotinic acid;
(E)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-yl) vinyl]-5-(3-methyl-but-2-ene base) nicotinic acid methyl ester;
(E)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-yl) vinyl]-5-(3-methyl-but-2-ene base) nicotinic acid;
(E)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-(2-thiazol-2-yl-vinyl)-phenol;
(E)-5-[2-(1H-imidazoles-2-yl) vinyl]-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol;
(E)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-(2-oxazole-2-base vinyl)-phenol;
(E)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-[2-(1H-pyrroles-2-yl)-vinyl]-phenol;
(E)-5-(2-biphenyl-4-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol;
(E)-5-(2-furans-2-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol;
(E)-4-{2-[3-hydroxy-5-methyl oxygen base-4-(3-methyl-but-2-ene base)-phenyl]-vinyl }-benzene-1,2-glycol;
(E)-4-{2-[3-hydroxy-5-methyl oxygen base-4-(3-methyl-but-2-ene base)-phenyl]-vinyl }-benzene-1,3-glycol;
(E)-3-methoxyl group-5-[2-(6-methoxypyridine-3-yl)-vinyl]-2-(3-methyl-but-2-ene base)-phenol;
(E)-5-(2-(4,6-dimethoxy-pyridine-3-yl) vinyl]-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol;
(E)-3-methoxyl group-5-[2-(2-methoxypyridine-4-yl)-vinyl]-2-(3-methyl-but-2-ene base)-phenol;
(E)-5-(2-(2,5-dimethoxy-pyridine-4-yl) vinyl]-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol;
(E)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-[2-(1H-pyrroles-3-yl)-vinyl]-phenol;
(E)-3-methoxyl group-5-[2-(5-methoxyl group-1H-pyrroles-3-yl)-vinyl]-2-(3-methyl-but-2-ene base)-phenol;
(E)-5-(2-furans-3-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol;
(E)-3-methoxyl group-5-[2-(4-methoxyl group furans-3-yl)-vinyl]-2-(3-methyl-but-2-ene base)-phenol;
(E)-5-[2-(2H-imidazol-4 yl) vinyl]-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol;
(E)-3-methoxyl group-5-[2-(5-methoxyl group-2H-imidazol-4 yl)-vinyl]-2-(3-methyl-but-2-ene base)-phenol;
(E)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-(2-thiazole-5-base-vinyl)-phenol;
(E)-3-methoxyl group-5-[2-(4-methoxyl group-thiazole-5-yl)-vinyl]-2-(3-methyl-but-2-ene base)-phenol;
(E)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-(2-oxazole-5-base-vinyl)-phenol;
(E)-3-methoxyl group-5-[2-(2-methoxyl group-oxazole-5-yl)-vinyl]-2-(3-methyl but-2-ene base)-phenol;
(E)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-styryl-pyridine-4-alcohol;
(E)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-pyridine-2-base-vinyl)-pyridine-4-alcohol;
(E)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-pyridin-3-yl-vinyl)-pyridine-4-alcohol;
(E)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-pyridin-4-yl-vinyl)-pyridine-4-alcohol;
(E)-6-(2-furans-2-base-vinyl)-2-methoxyl group-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol;
(E)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-pyridine-4-alcohol;
(E)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-pyridine-4-alcohol;
(E)-6-[2-(1H-imidazoles-2-yl)-vinyl]-2-methoxyl group-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol;
(E)-2-methoxyl group-6-[2-(5-methoxypyridine-2-yl)-vinyl]-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol;
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-methyl benzoate;
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-phenylformic acid;
(Z)-2-hydroxyl-6-[2-(1H-imidazoles-2-yl)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(Z)-2-hydroxyl-6-[2-(1H-imidazoles-2-yl)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-methyl benzoate;
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-phenylformic acid;
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-methyl benzoate;
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-phenylformic acid;
(Z)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(Z)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(Z)-6-(2-furans-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(Z)-6-(2-furans-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(Z)-6-[2-(3,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(Z)-6-[2-(3,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(Z)-6-[2-(2,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-methyl benzoate;
(Z)-6-[2-(2,4-dihydroxyl-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-phenylformic acid;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-styryl-nicotinic acid methyl ester;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-styryl-nicotinic acid;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridine-2-base-vinyl)-nicotinic acid methyl ester;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridine-2-base-vinyl)-nicotinic acid;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridin-3-yl-vinyl)-nicotinic acid methyl ester;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridin-3-yl-vinyl)-nicotinic acid;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridin-4-yl-vinyl)-nicotinic acid methyl ester;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridin-4-yl-vinyl)-nicotinic acid;
(Z)-2-(2-furans-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid methyl ester;
(Z)-2-(2-furans-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-nicotinic acid;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid methyl ester;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-[2-(1H-pyrroles-2-yl)-vinyl]-nicotinic acid;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-thiazol-2-yl-vinyl-nicotinic acid methyl ester;
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-thiazol-2-yl-vinyl-nicotinic acid;
(Z)-4-hydroxyl-2-[2-(1H-imidazoles-2-yl)-vinyl]-6-methoxyl group-5-(3-methyl-but-2-ene base)-nicotinic acid methyl ester;
(Z)-4-hydroxyl-2-[2-(1H-imidazoles-2-yl)-vinyl]-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid;
(Z)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-yl) vinyl]-5-(3-methyl-but-2-ene base) nicotinic acid methyl ester;
(Z)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-yl) vinyl]-5-(3-methyl-but-2-ene base) nicotinic acid;
(Z)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-(2-thiazol-2-yl-vinyl)-phenol;
(Z)-5-[2-(1H-imidazoles-2-yl) vinyl]-3-methoxyl group-2-(3-first-Ji but-2-ene base)-phenol;
(Z)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-(2-oxazole-2-base vinyl)-phenol;
(Z)-3-methoxyl group-2-(3-methyl-but-2-ene base)-5-[2-(1H-pyrroles-2-yl)-vinyl]-phenol;
(Z)-5-(2-biphenyl-4-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol;
(Z)-5-(2-furans-2-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol;
(Z)-4-{2-[3-hydroxy-5-methyl oxygen base-4-(3-methyl-but-2-ene base)-phenyl]-vinyl }-benzene-1,2-glycol
(Z)-4-{2-[3-hydroxy-5-methyl oxygen base-4-(3-methyl-but-2-ene base)-phenyl]-vinyl }-benzene-1,3-glycol
(Z)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-styryl-pyridine-4-alcohol;
(Z)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-pyridine-2-base-vinyl)-pyridine-4-alcohol;
(Z)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-pyridin-3-yl-vinyl)-pyridine-4-alcohol;
(Z)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-pyridin-4-yl-vinyl)-pyridine-4-alcohol;
(Z)-6-(2-furans-2-base-vinyl)-2-methoxyl group-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol;
(Z)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles-2-yl)-vinyl]-pyridine-4-alcohol;
(Z)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-pyridine-4-alcohol;
(Z)-6-[2-(1H-imidazoles-2-yl)-vinyl]-2-methoxyl group-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol;
(Z)-2-methoxyl group-6-[2-(5-methoxypyridine-2-yl)-vinyl]-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base amino)-6-styryl-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base amino)-6-styryl-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-butyl amino)-6-styryl-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-butyl amino)-6-styryl-phenylformic acid;
(E)-3-butoxy-2-hydroxyl-4-methoxyl group-6-styryl-methyl benzoate;
(E)-3-butoxy-2-hydroxyl-4-methoxyl group-6-styryl-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-butoxy)-6-styryl-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-butoxy)-6-styryl-phenylformic acid;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene oxygen base)-6-styryl-methyl benzoate;
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene oxygen base)-6-styryl-phenylformic acid.
4. the method in preparation claim 1 with the compound of structure shown in general formula (I), comprising:
Work as R 1for carboxyl or hydrogen, R 2for hydroxyl, R 3for halohydrocarbon, R 4for alkoxyl group, R 5for H, X is C, and all the other groups are while defining as claim 1 formula of, and its synthetic method is as route 1:
Route 1: the condensation under alkaline condition of acetylacetic ester and dicthenone obtains compound 2, compound 2 under alkaline condition in dipolar aprotic solvent alkylation generate compound 3, in non-polar solvent, there is free radical halogenating reaction and generate compound 4 in compound 3, compound 4 obtains compound 5 with tricresyl phosphite ester condensation, compound 5 obtains compound 6 with ketone or aldehyde reaction, compound 6 takes off alkyl again and obtains compound 7 under de-alkyl reagent exists, compound 7 obtains compound 8 with halohydrocarbon generation condensation reaction, compound 8 hydrolysis obtain compound of Formula I 9, compound 9 obtains compound of Formula I 10 by decarboxylic reaction under alkaline condition, wherein R 8, R 9, R 10for replacement or the unsubstituted alkyl of 1-18 carbon, R 3, R 6identical with the definition in claim 1 general formula,
Work as R again, 1for carboxyl or hydrogen, R 2for hydroxyl, R 3for halohydrocarbon, R 4for alkoxyl group, R 6for H, X is C, and all the other groups are while defining as claim 1 general formula, and its synthetic method is as route 2:
Route 2:
Route 2: the condensation under alkaline condition of acetylacetic ester and dicthenone obtains compound 2, compound 2 under alkaline condition in dipolar aprotic solvent alkylation generate compound 3, in non-polar solvent, there is free radical halogenating reaction and generate compound 4 in compound 3, compound 4 obtains compound 5 with tricresyl phosphite ester condensation, compound 5 obtains compound 6 with ketone or aldehyde reaction, compound 6 carries out dehydrogenation reaction and generates compound 11 under catalyst action, compound 11 under the effect of catalyzer in polar solvent reacting generating compound 12, compound 12 de-alkyl under de-alkyl reagent exists obtains compound 13, compound 13 obtains compound 14 with halohydrocarbon generation condensation reaction, compound 14 hydrolysis obtain compound of Formula I 15, compound 15 obtains compound of Formula I 16 by decarboxylic reaction under alkaline condition.Wherein R 8, R 9, R 10for replacement or the unsubstituted alkyl of 1-18 carbon, R 3, R 6identical with the definition in claim 1 general formula;
Work as R again, 1for carboxyl or hydrogen, R 2for hydroxyl, R 3for halohydrocarbon, R 4for alkoxyl group, R 5for H, X is N, and all the other groups are while defining as claim 1 general formula, and its synthetic method is as route 3:
Route 3:
1, 3-propanedioic acid and 2, 4, under the condition that 6-Trichlorophenol exists in phosphorus oxychloride, be condensed into compound 17, compound 17 and 2-amino-butenate reacting generating compound 18 in polar aprotic solvent, compound 18 alkylation under alkaline condition generates compound 19, in non-polar solvent, there is free radical halogenating reaction and generate compound 20 in compound 19, compound 20 is reacting generating compound 21 in phosphorous acid ester, compound 21 obtains compound 22 with ketone or aldehyde reaction, compound 22 takes off alkyl again and obtains compound 23 under de-alkyl reagent exists, compound 23 obtains 24 with halohydrocarbon generation condensation reaction, compound 24 hydrolysis obtain the compound 25 of general formula I, compound 25 obtains the compound 26 of general formula I by decarboxylic reaction under alkaline condition, wherein R 8, R 9, R 10for replacement or the unsubstituted alkyl of 1-18 carbon, R 3, R 6identical with the definition in claim 1 general formula.
Work as R again, 1for carboxyl or hydrogen, R 2for hydroxyl, R 3for halohydrocarbon, R 4for alkoxyl group, R 6for H, X is N, and all the other groups while defining as claim 1 general formula its synthetic method as route 4:
Route 4:
1, 3-propanedioic acid and 2, 4, under the condition that 6-Trichlorophenol exists at catalyzer, be condensed into compound 17, compound 17 and 2-amino-butenate reacting generating compound 18 in polar aprotic solvent, compound 18 alkylation under alkaline condition generates compound 19, in non-polar solvent, there is free radical halogenating reaction and generate compound 20 in compound 19, compound 20 is reacting generating compound 21 in phosphorous acid ester, compound 21 reacts with aldehydes or ketones and obtains compound 22, compound 22 carries out dehydrogenation reaction and generates compound 22 ' under alkali and bromine effect, compound 22 ' under the effect of catalyzer in polar solvent reacting generating compound 27, compound 27 de-alkyl under de-alkyl reagent exists obtains compound 28, compound 28 obtains compound 29 with halohydrocarbon generation condensation reaction, compound 29 hydrolysis obtain the compound 30 of general formula I, compound 30 obtains compound of Formula I 31 by decarboxylic reaction under alkaline condition.Wherein R 8, R 9, R 10for replacement or the unsubstituted alkyl of 1-18 carbon, R 3, R 6identical with the definition in claim 1 general formula.
Work as R again, 1for carboxyl or hydrogen, R 2for hydroxyl, R 3for alkylamino, R 4for alkoxyl group, R 5for H, and all the other groups are while defining as claim 1 general formula, and its synthetic method is as route 5:
Route 5:
The condensation under alkaline condition of acetylacetic ester and crotonate obtain compound 32 compounds 38 again bromination aromatic ring obtain compound 33, compound 33 again alkylation obtains compound 34, compound 34 obtains compound 35 with halide reagent generation free radical halogenating reaction, compound 35 obtains compound 36 with the condensation of organic phosphine reagent, there is substitution reaction and obtain alkylate 37 in compound 36, compound 37 obtains compound 38 with benzaldehyde under alkaline condition, there is again dealkylation and obtain compound 39 in compound 38, compound 39 obtains compound 40 through hydrolysis reaction.Wherein R 8, R 9, R 11for replacement or the unsubstituted alkyl of 1-18 carbon, Y is N, R 6identical with the definition in claim 1 general formula.
5. the compound with structure as shown in general formula I claimed in claim 1 or its pharmacy acceptable salt are in the application of preparing in anti-virus infection medicine.
6. application as claimed in claim 5, wherein, described virus comprises influenza virus, cells of coxsackie B 3 virus, hiv virus, hepatitis B virus and hepatitis C virus.
7. an antiviral medicinal composition, its activeconstituents comprises compound or its pharmacy acceptable salt with structure shown in general formula I claimed in claim 1.
8. pharmaceutical composition as claimed in claim 7, wherein, compound or the weight content of its pharmacy acceptable salt in this pharmaceutical composition with structure shown in general formula I are 0.1%-99.5%.
9. pharmaceutical composition as claimed in claim 8, wherein, compound or the weight content of its pharmacy acceptable salt in this pharmaceutical composition with structure shown in general formula I are 0.5%-99.5%.
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