CN103992290B - Diarylethene structurally similar compounds and its preparation method and application - Google Patents

Diarylethene structurally similar compounds and its preparation method and application Download PDF

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CN103992290B
CN103992290B CN201410203747.7A CN201410203747A CN103992290B CN 103992290 B CN103992290 B CN 103992290B CN 201410203747 A CN201410203747 A CN 201410203747A CN 103992290 B CN103992290 B CN 103992290B
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methyl
methoxyl group
vinyl
hydroxyl
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CN103992290A (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 one group of diarylethene structurally similar compounds and its preparation method and application.Compound provided by the present invention has the structure of formula I, present invention also offers in addition containing the described compound pharmaceutical composition as active component；Research finds, the compounds of this invention has resisiting influenza virus, cells of coxsackie B 3 virus, HIV (human immunodeficiency virus), hepatitis B virus, the pharmacologically active of hepatitis C virus etc., therefore, further, the present invention proposes described compound and contains the application in preparation antiviral drugs of this compounds pharmaceutical composition as active component.The present invention is that further investigation from now on is laid a good foundation with developing the application as clinical medicine of the described compound.

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, further relate to the application in the medicines such as resisiting influenza virus infection, cells of coxsackie B 3 virus, HIV (human immunodeficiency virus), hepatitis B virus, hepatitis C virus of the described compound.And containing this compounds as the pharmaceutical composition of active component and application thereof.The invention still further relates to the chemical total synthesis method of natural product cajanin analog.
Background technology
Semen Cajani (CajanuscajanL.Millsp.) is pulse family Semen Cajani platymiscium, for the sixth-largest Food Legume in the world, is also unique woody Food Legume.It is distributed mainly on the ground such as Southeast Asia, India, Burma and Yunnan Province of China, Sichuan, Jiangsu, Guangdong, Guangxi, Taiwan and Hainan.Wood bean has medical value widely, its seed primary efficacy has treatment Liver and kidney edema, stranguria with blood, hemorrhoid hematochezia etc., and root has the effects such as heat-clearing and toxic substances removing, dampness removing hemostasis, pain relieving, parasite killing, it is possible to treatment laryngopharynx swelling and pain, hemorrhoid hematochezia, stranguria with blood edema, dysuria etc..Folium Cajani is mainly used in treatment burn infection, wound, sore, jaundice, pain relieving and parasite killing etc. clinically.Folium Cajani is developed into the medicine for the treatment of ischemic necrosis of femoral head, in clinical treatment femur head necrosis safely and effectively.Chemical characteristic and the pharmacotoxicological effect result of study of wood bean prove, the iso-amylene substituted diaryl ethylene framework structured compound contained in Folium Cajani is mainly cajanin, Longistylin A and Longistylin C.The domestic bioactivity research bibliographical information about the water/alcohol extracts of Folium Cajani is more, and Folium Cajani extract has the multiple biological activitys such as antimetabolic disease disease, anti-cerebral ischemia anoxia-induced apoptosis, anti-inflammatory analgesic.
The activity of the osteoporosis of cajanin monomer and runic thing is confirmed, experimental result finds in 0.01～100mg/L mass concentration, Folium Cajani water extract can dose-dependently suppress the formation (P < 0.05) of osteoclast-like cell, also substantially suppresses the bone resorption activity (P < 0.05) of osteoclast-like cell simultaneously.
Luo Qingfeng etc. are investigated the treatment hyperlipemia effect of cajanin class formation analog, result shows that Folium Cajani extract can substantially reduce serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) level of abnormal rising in Mice Body, and without obvious toxic and side effects in effective dosage ranges.The antiinflammatory of Semen Cajani crude extract and analgesic activity also obtain the proof of experiment (referring to Chinese herbal medicine such as Sun Shaomei, 1995,26 (3:147-148), experimental result finds, laboratory sample cajanin preparation has obvious antiinflammatory action, effect is better than salicylic acid, and antiinflammatory action presents dose-dependence.The effect of vascular permeability is significantly reduced by cajanin preparation compared with matched group, it is suppressed that rate is 38.96%.Additionally, the influence research of the mice threshold of pain is found by cajanin preparation, gavage cajanin preparation high low dose group (200,120mg/kg), all can extend the mice threshold of pain, compared with before administration, extend more than one times, illustrate that cajanin preparation has obvious analgesic activity.
Natural product pharmacological research result shows, cajanin and Folium Cajani stilbene class extract have pharmacological action widely, and multiple mankind's major disease has stronger pharmacologically active (such as osteoporosis, hyperglycemia, hyperlipidemia, inflammation, tumor).Especially it has the mechanism of action (promoting bone growing simultaneously suppress bone resorption) that regulate bone metabolism balance similar to estrogen, and toxic and side effects is little, has more deep research at home.
But, the domestic and international chemical research about Semen Cajani stilbene class material is still confined to the Natural Medicine Chemistry aspects such as extracting and developing and the Structural Identification of natural product at present, and the quantity of the analog with clear and definite structure obtained is very limited.And, by the restriction of medicament sources, the further investigation of natural product cajanin pharmacological action is difficult to launch.The present inventor devises a series of cajanin compounds in the Chinese invention patent that application number is 201110439374.X and has carried out complete synthesis, and the multiformity for expanding such molecular structure of compounds further provides chemical means and basis.
Summary of the invention
First passage chemical means of the present invention, expands the multiformity of cajanin compounds molecular structure, synthesis, optimization Structures of Natural Products further；Synthesize the new compound in a large number with diarylethene structural framework first, and the cajanin analog derivative being synthetically derived has been carried out pharmacological action screening active ingredients, probe into the structure activity relationship disclosing this compounds；Research finds that this compounds has the activity (such as AntiHIV1 RT activity, HBV, HCV, influenza and Cox etc.) of strong antiviral widely.Realization for being optimized to medicine from activated natural product is laid a good foundation.
The present invention also completes the transformation to Longistylin A ring first；Meanwhile, on the basis of the patent application that application number is 201110439374.X, this compounds be also been proposed another brand-new complete synthesis route.
In order to achieve the above object, the present invention adopts the following technical scheme that
The invention provides the cajanin structurally similar compounds or its pharmaceutical salts that have as shown in formula I,
R in formula1Represent H, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, replacement or unsubstituted aryl, replacement or unsubstituted alkoxyl formyl or carboxyl.Preferably, selected from the phenyl replaced, benzyl, phenethyl, styryl.
R2Represent H, hydroxyl, replacement or unsubstituted alkoxyl, substituted or unsubstituted formyloxy, replacement or unsubstituted amino or halogen or isoureido.
R3Represent H, isopentene group, isopentyl, 3 ', 7 '-dimethyl-octa-2 ', 6 '-dialkylene, substituted or unsubstituted aryl, pi-allyl, halogen, substituted or unsubstituted amino.
R4Represent H, hydroxyl, replacement or unsubstituted alkoxyl, substituted or unsubstituted formyloxy, replacement or unsubstituted amino or halogen or isoureido.
R5Represent H, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, replacement or unsubstituted aryl, replacement or unsubstituted alkoxyl formyl or carboxyl；
R6Represent H, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, replacement or unsubstituted aryl, replacement or unsubstituted alkoxyl formyl or carboxyl；
In the present invention, it is preferred that
R1Selected from hydrogen, carboxyl, carbomethoxy；
R2Selected from hydroxyl, methoxyl group；
R3Selected from isopentene group, isopentyl, isopentene group amine, isoamylamine；
R5Selected from 2-furan, 2-thiazole, 2-imidazoles, 4-biphenyl, 2-pyridine, 3-pyridine, 4-pyridine, 6-methoxyl group-2-pyridine, 2,4-dihydroxy benzenes, 3,4-dihydroxy benzenes；
R6Selected from 2-pyrroles, 3-pyrroles, 2-methoxyl group-3-pyrroles, 2-furan, 3-furan, 2-methoxyl group-3-furan, 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 benzenes, 3,4-dihydroxy benzenes；
R7Selected from isopentene group, isopentyl.
Described in defined above:
" replacement " can be but not limited to by halogen, alkoxyl, hydroxyl, alkyl, amino, and alkyl amino replaces.Such as " substituted aryl " can be but not limited to: by halogen, alkoxyl, hydroxyl, alkyl, amino and substituted-amino etc. are replaced in the phenyl of various position.
" hetero-aromatic ring " can be but not limited to pyridine ring, thiazole ring, furan nucleus etc..
" alkyl " can be but not limited to the carbon number alkyl or cycloalkyl at the straight or branched of 1-18, such as, methyl, ethyl, isopropyl, n-pro-pyl, normal-butyl, isobutyl group, sec-butyl, the tert-butyl group, n-pentyl, isopentyl, n-hexyl, isohesyl etc. or its corresponding cycloalkyl.It is more preferably the low alkyl group of C1-C6.
" alkoxyl " can be but not limited to the carbon number alkoxyl at 1-18, such as, methoxyl group, ethyoxyl, isopropoxy, positive propoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy, isoamoxy, positive hexyloxy, different hexyloxy etc..It is more preferably C1-C6Lower alkoxy.
" acyl group " can be but not limited to hydrocarbon substituted acyl or the aryl-acyl with 1-18 carbon, for instance formoxyl, acetyl group, isopropyl acyl group, n-pro-pyl acyl group, pi-allyl acyl group, cyclopropyl acyl, normal-butyl acyl group, isobutyl group acyl group, sec-butyl acyl group, tert-butyl group acyl group, n-pentyl acyl group, isopentyl acyl group, n-hexyl acyl group, isohesyl acyl group, phenylacyl, tolyl acyl group etc..
" alkoxyl formyl " or " ester group " can be but not limited to hydrocarbon ester appended (alkylacyloxy) or the aryl ester group with 1-18 carbon, for instance formyloxy, acetoxyl group, isopropyl acyloxy, n-pro-pyl acyloxy, pi-allyl acyloxy, cyclopropyl acyloxy, normal-butyl acyloxy, isobutyl group acyloxy, sec-butyl acyloxy, tert-butyl group acyloxy, n-pentyl acyloxy, isopentyl acyloxy, n-hexyl acyloxy, isohesyl acyloxy, phenyl acyloxy, tolyl acyloxy etc..
" aminoacyl " or " carbamyl " can be have that the hydrocarbon of 1-18 carbon is monosubstituted or disubstituted aminoacyl or aryl aminoacyl, for instance N-methyl aminoacyl, ethyl aminoacyl, isopropyl aminoacyl, n-pro-pyl aminoacyl, pi-allyl aminoacyl, cyclopropyl aminoacyl, normal-butyl aminoacyl, isobutyl group aminoacyl, sec-butyl aminoacyl, tert-butyl group aminoacyl, n-pentyl aminoacyl, isopentyl aminoacyl, n-hexyl aminoacyl, isohesyl aminoacyl, phenylamino acyl group, tolyl aminoacyl etc..
" halo " or " halogen " can be fluorine, chlorine, bromine or iodine.
Present invention also offers the synthetic method of cajanin structurally similar compounds as shown in formula I, specific as follows.
The present invention provides the synthetic method of compound as shown in formula I:
Work as R1For carboxyl or hydrogen, R2For hydroxyl, R3For halogenated hydrocarbons, R4For alkoxyl, R5It is C and all the other groups such as its synthetic method such as route 1 when formula is defined above for H, X:
Route 1: the condensation in the basic conditions of acetoacetic ester and dicthenone obtains compound 2, compound 2 is alkylation generation compound 3 in dipolar aprotic solvent in the basic conditions, compound 3 occurs free radical halogenation to generate compound 4 in non-polar solven, compound 4 and tricresyl phosphite ester condensation obtain compound 5, compound 5 obtains compound 6 with ketone or aldehyde reaction, compound 6 takes off alkyl again under de-alkyl reagent exists and obtains compound 7, compound 7 and halogenated hydrocarbons generation condensation reaction obtain compound 8, compound 8 hydrolysis obtains compound of Formula I 9, compound 9 obtains compound of Formula I 10 by decarboxylic reaction under alkali condition；Wherein R8, R9,R10Replacement or unsubstituted alkyl, R for 1-18 carbon3,R6Identical with the definition in aforementioned each formula；
Route 2:
nullRoute 2: the condensation in the basic conditions of acetoacetic ester and dicthenone obtains compound 2，Compound 2 is alkylation generation compound 3 in dipolar aprotic solvent in the basic conditions，Compound 3 occurs free radical halogenation to generate compound 4 in non-polar solven，Compound 4 and tricresyl phosphite ester condensation obtain compound 5，Compound 5 obtains compound 6 with ketone or aldehyde reaction，Compound 6 carries out dehydrogenation reaction under catalyst action and generates compound 11，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 and halogenated hydrocarbons generation condensation reaction obtain compound 14，Compound 14 hydrolysis obtains compound of Formula I 15，Compound 15 obtains compound of Formula I 16 by decarboxylic reaction under alkali condition.
When preparing compound 4, described halide reagent can be but not limited to be SO2Cl2, NCS (i.e. N-chlorosuccinimide), NBS (i.e. N-bromosuccinimide), Br2Deng halide reagent, described solvent can be but not limited to CH2Cl2,CHCl3,CCl4Deng halogenated hydrocarbon solvent, or MeOH, EtOH, AcOH, propanol, isopropanol, n-butyl alcohol, tert-butyl alcohol isopolarity proton solvent, or acetonitrile, DMF polar aprotic solvent；
When preparing compound 11, described reagent can be but not limited to be F2,Cl2,Br2,I2, described alkali can be but not limited to KOH, NaOH, K2CO3, Na2CO3Deng inorganic base, described solvent can be but not limited to CH2Cl2,CHCl3,CCl4Deng halogenated hydrocarbon solvent, or MeOH, EtOH, AcOH, propanol, isopropanol, n-butyl alcohol, tert-butyl alcohol isopolarity proton solvent, or acetonitrile, DMF polar aprotic solvent.
When preparing compound 12, described catalyst can be but not limited to palladium, tetra-triphenylphosphine palladium, Pd/C, Pd/BaSO4, the solvent said can be but not limited to CH2Cl2,CHCl3,CCl4Deng halogenated hydrocarbon solvent, or acetonitrile, DMF polar aprotic solvent.
Again, the preparation method that present invention also offers formula I cajanin analog, as shown in Scheme 3:
Route three:
1, 3-malonic acid and 2, 4, 6-trichlorophenol, 2,4,6,-T is condensed into compound 17 under phosphorus oxychloride existent condition, compound 17 and 2-amino-butenate reacting generating compound 18 in polar non-solute, compound 18 alkylation in the basic conditions generates compound 19, compound 19 occurs free radical halogenation to generate compound 20 in non-polar solven, compound 20 reacting generating compound 21 in phosphite ester, compound 21 obtains compound 22 with ketone or aldehyde reaction, compound 22 takes off alkyl again under de-alkyl reagent exists and obtains compound 23, compound 23 and halogenated hydrocarbons generation condensation reaction obtain compound 24, compound 24 hydrolysis obtains compound of Formula I 25, compound 25 obtains compound of Formula I 26 by decarboxylic reaction under alkali condition；Wherein R8, R9Replacement or unsubstituted alkyl, R for 1-18 carbon3, R6, R8,R9Identical with the definition in aforementioned each formula.Described alkali can be but not limited to KOH, NaOH, K2CO3, Na2CO3Deng inorganic base, described acid can be but not limited to HCl, H2SO4, H3PO4Deng mineral acid, X is Cl, Br, I, and solvent can be but not limited to water, various alcohol isopolarity proton solvents or DMSO, DMF polar aprotic solvent；
When preparing compound 17, described condensing agent can be but not limited to be POCl3, DIC, DCC；Or HCl, H2SO4, BF3Various mineral acids or the lewis acid such as diethyl ether solution, described solvent can be but not limited to be CH2Cl2,CHCl3,CCl4Deng halogenated hydrocarbon solvent, or MeOH, EtOH, AcOH, propanol, isopropanol, n-butyl alcohol, tert-butyl alcohol isopolarity proton solvent, or acetonitrile, DMF polar aprotic solvent.
When preparing compound 18, described solvent can be but not limited to PhBr, acetonitrile, DMF polar aprotic solvent.
When preparing compound 19, described alkali condition can be but not limited to KOH, NaOH, K2CO3, Na2CO3Deng inorganic base, described alkylating reagent can be but not limited to alkyl chloride, bromoalkane, idoalkane, and described solvent can be but not limited to be acetonitrile, DMF polar aprotic solvent.
Again, the preparation method that present invention also offers formula I class cajanin, as shown in Scheme 4:
Route 4:
null1,3-malonic acid and 2,4,6-trichlorophenol, 2,4,6,-T is condensed into compound 17 under catalyst existent condition，Compound 17 and 2-amino-butenate reacting generating compound 18 in polar non-solute，Compound 18 alkylation in the basic conditions generates compound 19，Compound 19 occurs free radical halogenation to generate compound 20 in non-polar solven,Compound 20 reacting generating compound 21 in phosphite ester，Compound 21 and aldehyde reaction obtain compound 22，Compound 22 carries out dehydrogenation reaction under catalyst action and generates compound 22 '，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 and halogenated hydrocarbons generation condensation reaction obtain 29，Compound 29 hydrolysis obtains compound of Formula IV 30，Compound 30 obtains compound of Formula I 31 by decarboxylic reaction under alkali condition.Wherein R8, R9,R10Replacement or unsubstituted alkyl, R for 1-18 carbon3, R5Identical with the definition in aforementioned each formula.Described alkali can be but not limited to KOH, NaOH, K2CO3, Na2CO3Deng inorganic base, described acid can be but not limited to HCl, H2SO4, H3PO4Deng mineral acid, X is Cl, Br, I, and solvent can be but not limited to water, various alcohol isopolarity proton solvents or DMSO, DMF polar aprotic solvent；
Again, as R in formula I3Transformation, complementary basis group as defined in aforementioned formula time, its synthetic method as shown in Scheme 5:
Route 5:
Acetoacetic ester and crotonates condensation in the basic conditions obtain compound 32, compound 32 bromination is aromatic ring obtains compound 33, compound 33 alkylation obtains compound 34, compound 34 and halide reagent generation free radical halogenation obtain compound 35, compound 35 and organic phosphine reagent condensation obtain compound 36, compound 36 occurs substitution reaction to obtain alkylate 37, compound 37 obtains compound 38 with aldehydes or ketones condensation in the basic conditions, compound 38 occurs dealkylation to obtain 39, compound 39 obtains having the compound 40 of structure shown in formula (I) in preparation claim 1 through hydrolysis.
Invention effect:
Route and method as described above, the present invention has synthesized a large amount of Novel diaryl ethylene analog first, and the chemistry completing pyridine replacement cajanin first is complete synthesis, and trans cajanin also been proposed another brand-new complete synthesis route.The synthesized anti-resisiting influenza virus infection of cajanin derivant, cells of coxsackie B 3 virus, HIV (human immunodeficiency virus), hepatitis B virus, hepatitis C virus isoreactivity have also been measured by the present invention 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.
Adopting cell culture method that the antiviral activity of invention compound is screened to find, 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 significantly stronger than primer cajanin, further, compared with clinical medicine oseltamivir phosphate capsule, the antiviral activity of foregoing invention compound is quite even higher with oseltamivir phosphate capsule.
Table 1: the structure of invention compound and antiviral activity
NA represents does not have activity.
The invention still further relates to described compound at anti-COX-B3, the application of inhibition of HIV aspect, its result is in Table 2, wherein, compound 8d, 8g, 8k, 10b, 15b, 15h, 16h, 24i, 25i, 40e, 40d etc. show stronger anti-COX-B3, the activity of inhibition of HIV.
Table 2: the structure of invention compound and antiviral activity
The invention still further relates to described compound and suppress HBV, the application of HCV virus aspect, its result is in Table 3, wherein, the compounds such as compound 9n, 9o, 10g, 10l, 10m, 10o, 10t, 14g, 14h, 15b, 15c, 15f, 15g, 39c show stronger Anti-HBV activity, the activity of HCV virus.
Table 3: the structure of invention compound and antiviral activity
NA is not for having activity
The invention still further relates to the neuroprotective of described compound, function of resisting osteoporosis.Bibliographical information, Semen Cajani stilbene compound belongs to phytoestrogen, and it is relevant that the function of resisting osteoporosis of natural product has estrogen-like effects with it.Osteoporosis in ovariectomized rats protected effect has been carried out research confirmation by the present invention cajanin sterling to being obtained by chemical means, and result shows, its osteoporosis effect in animal body is better than clinical medicine Evista.
It addition, just as explained in the background of the invention, Semen Cajani stilbene class extract and cajanin, Longistylin A, Longistylin C have antitumor, reducing blood sugar and blood fat, anti-inflammatory and analgesic effect are widely studied and report.The analog that the compounds of this invention is is lead compound with natural product cajanin, Longistylin A, the compounds of this invention has the similar antitumor of primer simultaneously, reducing blood sugar and blood fat, anti-inflammatory and analgesic effect are apparent from.Therefore, the invention still further relates to the application in antitumor, reducing blood sugar and blood fat, anti-inflammatory and antalgic etc. of the described compound.
And; the present invention also provides for a kind of pharmaceutical composition for antiviral and antibacterial infection, neuroprotective, antimetabolic disease (such as osteoporosis, hyperlipidemia, hyperglycemia) etc.; there is described in this pharmaceutical composition comprises the compound or pharmaceutically acceptable salt thereof of formula I, also can further include one or more pharmaceutically acceptable pharmaceutical adjuvants.
Wherein, described in there is the compound or pharmaceutically acceptable salt thereof of formula I as active component, the weight content in this pharmaceutical composition is 0.1%-99.5%.Preferably, containing weight ratio in this pharmaceutical composition is the active component of 0.5%-99.5%.
Further, the present invention provides the application in the preparation medicine such as antibacterium and viral infection, neuroprotective, antimetabolic disease (such as osteoporosis, hyperlipidemia, hyperglycemia) of the described compositions.
Detailed description of the invention
Below in conjunction with specific embodiment further describe the present invention, advantages of the present invention and feature will be with describe and apparent.But these embodiments are only exemplary, the scope of the present invention is not constituted any restriction.It will be understood by those skilled in the art that and the details of technical solution of the present invention and form can be modified or replace lower without departing from the spirit and scope of the present invention, but these amendments and replacement each fall within protection scope of the present invention.
Embodiment 1
The preparation (2) of 2,4-dihydroxy-6-methyl toluates
Methyl acetoacetate (50g, 0.43mol) it is dissolved in 300ml ether, NaH (15.50g0.45mol is added in room temperature, 70%), finish, drip dicthenone (37g in this temperature, diethyl ether solution 0.45mol), finishing, at room temperature reaction 3-4h, now reaction system becomes yellow dirty solution.Terminating reaction, be added to by reactant liquor in 500ml frozen water mixed liquor, separate ether layer, water layer 50ml ether extracts 2 times, combined ether layer, and washes with saturated common salt, and anhydrous magnesium sulfate is dried overnight.Filtering, rotation is evaporated off ether, and residue petroleum ether: ethyl acetate=8:1 crosses silicagel column obtains 35g (45%) white solid and is target product.1H-NMR(400M,DMSO-d6) 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 toluates
Compound 2 (12g, 0.066mol) is dissolved in 50ml acetone, adds potassium carbonate (27.3g, 0.198mol), iodomethane (28g, 0.198mol), heating reflux reaction 3h, stopped reaction, reactant liquor adds in 100ml water, is extracted with ethyl acetate (350ml), merge organic layer, organic layer is successively with the sodium hydroxide solution of 10%, 10% hydrochloric acid, saturated common salt washing.Organic over anhydrous magnesium sulfate dries.Filtering, rotation is evaporated off solvent, obtains colorless oil, obtains clear crystal 13.5g (97%) with petrol ether/ethyl acetate recrystallization.1H-NMR(400M,CDCl3)δ(ppm):6.31(s,2H),3.88(s,3H),3.80(s,6H),2.28(s,3H)
Embodiment 3
2-bromomethyl-4,6-dimethoxy p-methyl (4)
Compound 3 (10g, 0.0476mol) is dissolved in 50ml carbon tetrachloride, and nitrogen protection is heated to reflux, and is dividedly in some parts the mixture of NBS (8.5g, 0.0476mol)+BPO (0.11g, 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,CDCl3)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 NSC 5284 (10.83g, 0.065mol), heating reflux reaction 2h.Stopped reaction, cooling, decompression boils off excessive NSC 5284, residue dichloromethane: methanol=40:1 crosses silicagel column and obtains white solid 12.8g (92%).1H-NMR(400M,CDCl3) 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] essence of Niobe (6)
Compound 5 (10g, 0.0289mol) is dissolved in 100ml oxolane, adds NaH (1.09g, 0.0318mol), benzaldehyde (3.68g, 0.0347mol), heating reflux reaction 2h, stopped reaction, reactant liquor joins in 200ml water, is extracted with ethyl acetate (3100ml), merges organic layer, organic layer saturated common salt is washed, and anhydrous magnesium sulfate dries.Filtering, rotation boils off except solvent, and residue grease petrol ether/ethyl acetate recrystallization obtains clear crystal 6.2g (72%).1H-NMR(400M,CDCl3) 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] essence of Niobe (7)
Compound 6 (6g, 0.0201mol) is dissolved in 50ml dichloromethane, drips BBr when 0 DEG C3Dichloromethane solution (24ml, 1M), drip off, room temperature reaction 1h, stopped reaction.Reactant liquor washes with water, and anhydrous magnesium sulfate dries.Filtering, rotation is evaporated off solvent, and residue petroleum ether/ethyl ether is crossed silicagel column and obtained white solid 5.4g (95%).1H-NMR(400M,CDCl3) 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] essence of Niobe (8)
Compound 7 (5g, 0.0176mol) it is dissolved in 50ml ether, adds metallic sodium (0.43g, 0.0184mol), 4h is stirred at room temperature, add isoprenyl bromide (3.2g, 0.0211mol), back flow reaction 4h, stopped reaction, reactant liquor priority water, saturated common salt is washed, and separates organic layer.Organic over anhydrous magnesium sulfate dries, and filters, and rotation boils off except solvent obtains yellow oil, crosses silicagel column and obtains white solid 3.8g (61%).1HNMR(400M,DMSO-d6) 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] benzoic acid (1, cajanin)
Compound 8 (3g, 0.0085mol) is dissolved in the sodium hydrate aqueous solution of 30ml20%, heating reflux reaction 2h, stopped reaction, cooling.The dilute hydrochloric acid adding 10% adjusts pH now to have a large amount of white precipitate to generate less than 2., filters, dries to obtain white solid, obtain white solid 2.6g (90%) with petrol ether/ethyl acetate recrystallization.1HNMR(400M,CDCl3) 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.Reactant liquor adds in 50ml water, and the salt acid for adjusting pH with 10%, less than 2, is extracted with ethyl acetate (3X30ml), merges organic layer, and organic layer is washed with saturated common salt again, and anhydrous magnesium sulfate is dried overnight.Next day filters, and concentrates to obtain light yellow solid, then crosses silicagel column by petrol ether/ethyl acetate, obtains white solid 0.66g (80%).1HNMR(400MHz,CDCl3): 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) essence of Niobe (6a)
With 2-thiazole benzaldehyde for raw material, obtain this compound, white solid (83%) with the method that embodiment 5 is similar.1HNMR(500MHz,CDCl3) δ 7.74 (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)-essence of Niobe (7a)
With compound 6a for raw material, it is obtained by reacting compound, white solid (95%) by the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 7.75 (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)-essence of Niobe (8a)；
With compound 7a for raw material, obtain compound 8a, white solid (62%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 7.76 (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)-benzoic acid (9a)；
With compound 8a for raw material, obtain compound 9a, white solid (90%) according to the method for embodiment 8.1HNMR (500MHz, CDCl3) δ 7.76 (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)；
With compound 9a for raw material, obtain compound 10a, white solid (86%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.75 (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-base)-vinyl]-4,6-dimethoxy p-methyl (6b)；
With 2-imidazoles benzaldehyde for raw material, obtain this compound, white solid (81%) with the method that embodiment 5 is similar.1HNMR (500MHz, CDCl3) δ 7.65 (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-base)-vinyl]-4-methoxy-benzoic acid methyl ester (7b)；
With compound 6b for raw material, it is obtained by reacting compound 7b, white solid (93%) by the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 7.46 (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-base)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe (8b)
With compound 7b for raw material, obtain compound 8b, white solid (54%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 7.65 (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-base)-vinyl]-4-methoxyl group-3-(3-methyl but-2-ene base)-benzoic acid (9b)
With compound 8b for raw material, obtain compound 9b, white solid (90%) according to the method for embodiment 8.1HNMR (500MHz, CDCl3) δ 7.50 (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-base) vinyl]-3-methoxyl group-2-(3-methyl but-2-ene base)-phenol (10b)
With compound 9b for raw material, obtain compound 10b, white solid (88%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.52 (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) essence of Niobe (6c)
With 2-oxazole benzaldehyde for raw material, it is obtained by reacting compound 6c, white solid (92%) by the method for embodiment 5.1HNMR (500MHz, CDCl3) δ 7.63 (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) essence of Niobe (7c)
With compound 6c for raw material, obtain compound 7c, white solid (96%) according to the method for embodiment 6.1HNMR(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)-essence of Niobe (8c)
With compound 7c for raw material, obtain compound 8c, white solid (70%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 9.04 (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)-benzoic acid (9c)
With compound 8c for raw material, obtain compound 9c, white solid (86%) according to the method for embodiment 8.1HNMR (500MHz, CDCl3) δ 7.69 (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)
With compound 9c for raw material, obtain compound 10c, white solid (95%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.67 (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's-2-base)-vinyl] essence of Niobe (6d)
With 2-pyrroles's benzaldehyde for raw material, it is obtained by reacting compound 6d, white solid (87%) by the method for embodiment 5.1HNMR(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's-2-base)-vinyl] essence of Niobe (7d)
With compound 6d for raw material, obtain compound 7d, white solid (96%) according to the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 9.75 (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's-2-base)-vinyl]-essence of Niobe (8d)
With compound 7d for raw material, obtain compound 8d, white solid (52%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 9.65 (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's-2-base)-vinyl]-benzoic acid (9d)
With compound 8d for raw material, obtain compound 9d, white solid (90%) 1HNMR (500MHz according to the method for embodiment 8, 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's-2-base)-vinyl]-phenol (10d)
With compound 9d for raw material, obtain compound 10d, white solid (89%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 9.72 (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)
With 4-phenyl benzaldehyde for raw material, obtain this compound, white solid (84%) with the method that embodiment 5 is similar.1HNMR(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-methoxy-benzoic acid methyl ester (7e)
With compound 6e for raw material, it is obtained by reacting compound 7e, white solid (92%) by the method for embodiment 6.1HNMR(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)-essence of Niobe (8e)
With compound 7e for raw material, obtain compound 8e, white solid (55%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 7.73 (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)-benzoic acid (9e)
With compound 8e for raw material, obtain compound 9e, white solid (77%) 1HNMR (500MHz according to the method for embodiment 8, 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)
With compound 9e for raw material, obtain compound 10e, white solid (91%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.68 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-furan-2-base-vinyl)-4,6-dimethoxy p-methyl (6f)
With 2 furan carboxyaldehyde for raw material, obtain this compound, white solid (84%) with the method that embodiment 5 is similar.1HNMR (500MHz, CDCl3) δ 7.60 (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-furan-2-base-vinyl)-6-hydroxyl-4-methoxy-benzoic acid methyl ester (7f)
With compound 6f for raw material, it is obtained by reacting compound 7f, white solid (92%) by the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 7.62 (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-furan-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-essence of Niobe (8f)
With compound 7f for raw material, obtain compound 8f, white solid (70%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 7.73 (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-furan-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-benzoic acid (9f)
With compound 8f for raw material, obtain compound 9f, white solid (88%) 1HNMR (500MHz according to the method for embodiment 8, 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-furan-2-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol (10f)
With compound 9f for raw material, obtain compound 10f, white solid (92%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.60 (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-dihydroxy-phenyl)-vinyl]-4,6-dimethoxy p-methyl (6g)
With 3,4-4-dihydroxy benzaldehydes for raw material, obtain this compound, white solid (88%) with the method that embodiment 5 is similar.1HNMR(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-dihydroxy-phenyl)-vinyl]-6-hydroxyl-4-methoxy-benzoic acid methyl ester (7g)
With compound 6g for raw material, it is obtained by reacting compound 7g, white solid (91%) by the method for embodiment 6.1HNMR(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-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-essence of Niobe (8g)
With compound 7g for raw material, obtain compound 8g, white solid (71%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 9.15 (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-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-benzoic acid (9g)
With compound 8g for raw material, obtain compound 9g, white solid (93%) 1HNMR (500MHz according to the method for embodiment 8, 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)
With compound 9g for raw material, obtain compound 10g, white solid (93%) according to the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 7.12 (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-dihydroxy-phenyl)-vinyl]-4,6-dimethoxy p-methyl (6h)
With 2,4-4-dihydroxy benzaldehydes for raw material, obtain this compound, white solid (80%) with the method that embodiment 5 is similar.1HNMR(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-dihydroxy-phenyl)-vinyl]-6-hydroxyl-4-methoxy-benzoic acid methyl ester (7h)
With compound 6h for raw material, it is obtained by reacting compound 7h, white solid (87%) by the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 7.65 (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-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-essence of Niobe (8h)
With compound 7h for raw material, it is obtained by reacting compound 8h, white solid (47%) by the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 8.78 (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-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-benzoic acid (9h)
With compound 8h for raw material, obtain compound 9h, white solid (89%) 1HNMR (500MHz according to the method for embodiment 8, 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)
With compound 9h for raw material, obtain compound 10h, white solid (94%) 1HNMR (500MHz according to the method for embodiment 9, 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-base)-vinyl] essence of Niobe (6i)
With 6-methoxypyridine-3-formaldehyde for raw material, obtain this compound, white solid (83%) with the method that embodiment 5 is similar.1HNMR (500MHz, Chloroform) δ 7.73 (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-base)-vinyl] essence of Niobe (7i)
With 6i for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.74 (s with the method that embodiment 6 is similar, 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-base)-vinyl]-3-(3-methyl but-2-ene base)-essence of Niobe (8i)
With 7i for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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-base)-vinyl]-3-(3-methyl but-2-ene base)-benzoic acid (9i)
With 8i for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 8 is similar, 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-base)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10i)
With 9i for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.70 (s with the method that embodiment 9 is similar, 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-base)-vinyl]-4,6-dimethoxy p-methyl (6j)
With 4,6-dimethoxy-pyridine-3-formaldehyde for raw material, obtain this compound, white solid (83%) with the method that embodiment 5 is similar.1HNMR(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-base)-vinyl]-6-hydroxyl-4-methoxy-benzoic acid methyl ester (7j)
With 7i for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.55 (s with the method that embodiment 6 is similar, 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-base)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe (8j)
With 7j for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 8.55 (s with the method that embodiment 7 is similar, 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-base)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid (9j)
With 8j for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 8 is similar, 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-base) vinyl]-3-methoxyl group-2-(3-methyl but-2-ene base)-phenol (10j)
With 9j for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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-base)-vinyl] essence of Niobe (6k)
With 2-methoxypyridine-4-formaldehyde for raw material, obtain this compound, white solid (83%) with the method that embodiment 5 is similar.1HNMR(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-base)-vinyl] essence of Niobe (7k)
With 6k for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.64 (m with the method that embodiment 6 is similar, 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-base)-vinyl]-3-(3-methyl but-2-ene base)-essence of Niobe (8k)
With 7k for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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-base)-vinyl]-3-(3-methyl but-2-ene base)-benzoic acid (9k)
With 8k for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.84 7.59 (m with the method that embodiment 8 is similar, 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-base)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10k)
With 9k for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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-base)-vinyl]-4,6-Dimethoxy-benzoic acid methyl ester (6l)
With 2,5-dimethoxy-pyridine-4-formaldehyde for raw material, obtain this compound, white solid (83%) with the method that embodiment 5 is similar.1HNMR (500MHz, Chloroform) δ 7.41 (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-base)-vinyl]-6-hydroxyl-4-methoxy-benzoic acid methyl ester (7l)
With 6l for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.48 (s with the method that embodiment 6 is similar, 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-base)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-essence of Niobe (8l)
With 7l for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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-base)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-benzoic acid (9l)
With 8l for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 8 is similar, 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-base) vinyl]-3-methoxyl group-2-(3-methyl but-2-ene base)-phenol
With 9l for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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's-3-base)-vinyl] essence of Niobe (6m)
With 1H-pyrroles's-3-formaldehyde for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.24 (s with the method that embodiment 5 is similar, 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's-3-base)-vinyl] essence of Niobe (7m)
With 6m for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.34 (d with the method that embodiment 6 is similar, 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's-3-base) vinyl] essence of Niobe (8m)
With 7m for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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's-3-base) vinyl] benzoic acid (9m)
With 8m for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 8 is similar, 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's-3-base)-vinyl]-phenol (10m)
With 9m for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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's-3-base)-vinyl] essence of Niobe (6n)
With 5-methoxyl group-1H-pyrroles's-3-formaldehyde for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.26 (s with the method that embodiment 5 is similar, 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's-3-base)-vinyl] essence of Niobe (7n)
With 6n for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 6 is similar, 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's-3-base)-vinyl]-3-(3-methyl but-2-ene base)-essence of Niobe
With 7n for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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's-3-base)-vinyl]-3-(3-methyl but-2-ene base)-benzoic acid (9n)
With 8n for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.78 (s with the method that embodiment 8 is similar, 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's-3-base)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10n)
With 9n for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.36 (s with the method that embodiment 9 is similar, 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-furan-3-base-vinyl)-4,6-dimethoxy p-methyl (6o)
With furan-3-formaldehyde for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.93 (s with the method that embodiment 5 is similar, 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-furan-3-base-vinyl)-6-hydroxyl-4-methoxy-benzoic acid methyl ester (7o)
With 6o for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.93 (s with the method that embodiment 6 is similar, 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-furan-3-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-essence of Niobe (8o)
With 7o for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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-furan-3-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-benzoic acid (9o)
With 8o for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 8 is similar, 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-furan-3-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol (10o)
With 9o for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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 furan-3-base)-vinyl] essence of Niobe (6p)
With 4-methoxyl group-furan-3-formaldehyde for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 5 is similar, 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-furan-3-base)-vinyl] essence of Niobe (7p)
With 6p for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 6 is similar, 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 furan-3-base)-vinyl]-3-(3-methyl but-2-ene base)-essence of Niobe (8p)
With 7p for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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 furan-3-base)-vinyl]-3-(3-methyl but-2-ene base)-benzoic acid (9p)
With 8p for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 8 is similar, 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 furan-3-base)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10p)
With 9p for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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)
With 2H-imidazoles-4-formaldehyde for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.07 (s with the method that embodiment 5 is similar, 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-methoxy-benzoic acid methyl ester (7q)
With 6q for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 6 is similar, 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)-essence of Niobe (8q)
With 7q for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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)-benzoic acid (9q)
With 8q for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 8 is similar, 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)
With 9q for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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] essence of Niobe (6r)
With 5-methoxyl group-2H-imidazoles-4-formaldehyde for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 5 is similar, 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] essence of Niobe (7r)
With 6r for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 6 is similar, 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)-essence of Niobe (8r)
With 7r for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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)-essence of Niobe (9r)
With 8r for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 8 is similar, 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
With 9r for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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)-essence of Niobe (6s)
With thiazole-5-formaldehyde for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 5 is similar, 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)-essence of Niobe (7s)
With 6s for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 6 is similar, 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)-essence of Niobe
With 7s for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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)-benzoic acid (9s)
With 8s for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 8 is similar, 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)
With 9s for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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-base)-vinyl] essence of Niobe
With 4-methoxyl group-thiazole-5-formaldehyde for raw material, obtain this compound, white solid (6t) 1HNMR (500MHz, Chloroform) δ 8.73 (s with the method that embodiment 5 is similar, 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-base)-vinyl] essence of Niobe (7t)
With 6t for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 6 is similar, 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-base)-vinyl]-3-(3-methyl but-2-ene base)-essence of Niobe (8t)
With 7t for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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-base)-vinyl]-3-(3-methyl but-2-ene base)-benzoic acid (9t)
With 8t for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 9.04 (s with the method that embodiment 8 is similar, 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-base)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10t)
With 9t for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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)-essence of Niobe (6u)
With oxazole-5-formaldehyde for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 5 is similar, 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)-essence of Niobe (7u)
With 6u for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.90 (s with the method that embodiment 6 is similar, 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)-essence of Niobe (8u)
With 7u for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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)-benzoic acid (9u)
With 8u for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 8 is similar, 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)
With 9u for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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-base)-vinyl] essence of Niobe (6v)
With 2-methoxyl group-oxazole-5-formaldehyde for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 5 is similar, 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-base)-vinyl] essence of Niobe (7v)
With 6v for raw material, obtain this compound, white solid 1HNMR (500MHz, Chloroform) δ 7.30 (s with the method that embodiment 6 is similar, 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-base)-vinyl]-3-(3-methyl but-2-ene base)-essence of Niobe (8v)
With 7v for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 7 is similar, 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-base)-vinyl]-3-(3-methyl but-2-ene base)-benzoic acid (9v)
With 8v for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 8 is similar, 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-base)-vinyl]-2-(3-methyl but-2-ene base)-phenol (10v)
With 9v for raw material, obtain this compound, white solid 1HNMR (500MHz with the method that embodiment 9 is similar, 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 acetenyl-essence of Niobe (11a)
Under room temperature, compound 6a (40g, 0.131mol) is dissolved in dehydrated alcohol, adding bromine (42g, 0.262mol), heating is to 70 DEG C, 2h, after cold room temperature processed, gradually 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 is washed, and anhydrous magnesium sulfate is dried overnight.Filtering, rotation is evaporated off ethyl acetate, residue petroleum ether: ethyl acetate=7:1 crosses silicagel column, obtain compound 11a (31.2g, 80%) white solid .1HNMR (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) essence of Niobe (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, 60psi, stops reaction after 2h, being steamed by dehydrated alcohol, acetic acid ethyl dissolution system, saturated common salt is washed, and anhydrous magnesium sulfate is dried overnight.Filtering, rotation is evaporated off ethyl acetate, and residue petroleum ether: ethyl acetate=10:1 crosses silicagel column obtains compound 12a (21.3g, 85%) white solid 1HNMR (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)-essence of Niobe (13a)
With compound 12a for raw material, obtain compound 13a, white solid (95%) 1HNMR (500MHz according to the method that embodiment 6 is similar, 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)-essence of Niobe (14a)；
With compound 13a for raw material, obtain compound 14a, white solid (56%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 9.04 (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)-benzoic acid (15a)；
With compound 14a for raw material, obtain compound 15a, white solid (80%) according to the method for embodiment 8.1HNMR (500MHz, CDCl3) δ 8.78 (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)；
With compound 15a for raw material, obtain compound 16a, white solid (88%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.76 (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-essence of Niobe (11b)
Compound 11b, white solid (87%) 1HNMR (500MHz, Chloroform) δ 7.30 (s is obtained for raw material according to the method for embodiment 120 with 6b, 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) essence of Niobe (12b)
With compound 11b for raw material, obtain compound 12b, white solid (87%) 1HNMR (500MHz, CDCl3) δ 7.65 (s according to the method for embodiment 121,1H), 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-base)-vinyl]-4-methoxy-benzoic acid methyl ester (13b)
With compound 12b for raw material, obtain compound 13b, white solid (95%) 1HNMR (500MHz according to the method that embodiment 6 is similar, 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-base)-vinyl]-4-methoxyl group-3-(3-methyl but-2-ene base)-essence of Niobe (14b)
With compound 13b for raw material, obtain compound 14b, white solid (60%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 9.04 (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-base)-vinyl]-4-methoxyl group-3-(3-methyl but-2-ene base)-benzoic acid (15b)
With compound 14b for raw material, obtain compound 15b, white solid (89%) according to the method for embodiment 8.1HNMR (500MHz, CDCl3) δ 8.75 (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-base) vinyl]-3-methoxyl group-2-(3-methyl but-2-ene base)-phenol (16b)
With compound 15b for raw material, obtain compound 16b, white solid (93%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.65 (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-essence of Niobe (11c)
Compound 11c is obtained for raw material according to the method for embodiment 120 with 6c, white solid (85%) 1HNMR (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) essence of Niobe (12c)
With compound 11c for raw material, obtain compound 12c, white solid (86%) 1HNMR (500MHz according to the method for embodiment 121, 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)-essence of Niobe (13c)
With compound 12c for raw material, obtain compound 13c, white solid (77%) 1HNMR (500MHz according to the method that embodiment 6 is similar, 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)-essence of Niobe (14c)
With compound 13c for raw material, obtain compound 14c, white solid (74%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 7.63 (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)-benzoic acid (15c)
With compound 14c for raw material, obtain compound 15c, white solid (86%) according to the method for embodiment 8.1HNMR(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)
With compound 15c for raw material, obtain compound 16c, white solid (97%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.64 (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's-2-ethyl-acetylene base-essence of Niobe (11d)
Compound 11d, white solid (82%) 1HNMR (500MHz, Chloroform) δ 7.46 (s is obtained for raw material according to the method for embodiment 120 with 6d, 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's-2-base vinyl) essence of Niobe (12d)
With compound 11b for raw material, obtain compound 12d, white solid (75%) 1HNMR (500MHz according to the method for embodiment 121, 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)-essence of Niobe (13d)
With compound 12d for raw material, obtain compound 13d, white solid (90%) 1HNMR (500MHz, CDCl3) δ 9.63 (s according to the method that example 6 is similar, 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's-2-base)-vinyl]-essence of Niobe (14d)
With compound 13d for raw material, obtain compound 14d, white solid (59%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 9.68 (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's-2-base)-vinyl]-benzoic acid (15d)
With compound 14d for raw material, obtain compound 15d, white solid (79%) 1HNMR (500MHz according to the method for embodiment 8, 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's-2-base)-vinyl]-phenol (16d)
With compound 15d for raw material, obtain compound 16d, white solid (87%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 9.64 (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-benzoic acid methyl ester (11e)
Compound 11e, white solid (77%) 1HNMR (500MHz, Chloroform) δ 7.78 7.74 (m is obtained for raw material according to the method for embodiment 120 with 6e, 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)
With compound 11e for raw material, obtain compound 12e, white solid (91%) 1HNMR (500MHz according to the method for embodiment 121, 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-methoxy-benzoic acid methyl ester (13e)
With compound 13d for raw material, obtain compound 13e, white solid (82%) 1HNMR (500MHz, CDCl3) δ 7.64 7.57 (m according to the method that embodiment 6 is similar, 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)-essence of Niobe (14e)
With compound 13e for raw material, obtain compound 14e, white solid (57%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 9.04 (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)-benzoic acid (15e)
With compound 14e for raw material, obtain compound 15e, white solid (88%) 1HNMR (500MHz according to the method for embodiment 8, 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)
With compound 15e for raw material, obtain compound 16e, white solid (80%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.77 (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-furan-2-ethyl-acetylene base-essence of Niobe (11f)
Compound 11f, white solid (91%) 1HNMR (500MHz, Chloroform) δ 7.58 (s is obtained for raw material according to the method for embodiment 120 with 6f, 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 furan-2-base vinyl) essence of Niobe (12f)
With compound 11f for raw material, obtain compound 12f according to the method for embodiment 121.(87%) 1HNMR (500MHz, CDCl3) δ 7.57 (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)-essence of Niobe (13f)
With compound 12f for raw material, obtain compound 13f, white solid (91%) according to the method that embodiment 6 is similar.1HNMR (500MHz, CDCl3) δ 7.61 (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-furan-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-essence of Niobe (14f)
With compound 13f for raw material, obtain compound 14f, white solid (63%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 9.04 (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-furan-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-benzoic acid (15f)
With compound 14f for raw material, obtain compound 15f, white solid (80%) 1HNMR (500MHz according to the method for embodiment 8, 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-furan-2-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol (16f)
With compound 15f for raw material, obtain compound 16f, white solid (86%) according to the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.63 (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-dihydroxy-phenylene-ethynylene)-4,6-dimethoxy p-methyl (11g)
Compound 11g, white solid (87%) 1HNMR (500MHz, Chloroform) δ 7.31 (d is obtained for raw material according to the method that embodiment 120 is similar with 6g, 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-dihydroxy-phenyl)-vinyl]-4,6-dimethoxy p-methyl (12g)
With compound 11g for raw material, obtain compound 12g, white solid (75%) 1HNMR (500MHz, CDCl3) δ 7.06 (d according to the method for embodiment 121, 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-dihydroxy-phenyl)-vinyl]-6-hydroxyl-4-methoxy-benzoic acid methyl ester (13g)
With compound 12g for raw material, obtain compound 13g (95%) .1HNMR (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-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-essence of Niobe (14g)
With compound 13g for raw material, obtain compound 14g, white solid (53%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 7.86 (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-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-benzoic acid (15g)
With compound 14g for raw material, obtain compound 15g, white solid (82%) 1HNMR (500MHz according to the method for embodiment 8, 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)
With compound 15g for raw material, obtain compound 16g, white solid (76%) according to the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 7.13 (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-dihydroxy-phenylene-ethynylene)-4,6-dimethoxy p-methyl (11h)
Compound 11h, white solid (87%) 1HNMR (500MHz, Chloroform) δ 7.39 (d is obtained according to the method that embodiment 120 is similar with 6h raw material, 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-dihydroxy-phenyl)-vinyl]-4,6-dimethoxy p-methyl (12h)
With compound 11h for raw material, obtain compound 12h, white solid (78%) according to the method for embodiment 121.1HNMR (500MHz, CDCl3) δ 7.63 (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-dihydroxy-phenyl)-vinyl]-6-hydroxyl-4-methoxy-benzoic acid methyl ester (13h).
With compound 12h for raw material, obtain compound 13h (85%) according to the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 7.58 (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-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-essence of Niobe (14h)
With compound 13h for raw material, obtain compound 14h, white solid (51%) according to the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 7.86 (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-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl but-2-ene base)-benzoic acid (15h)
With compound 14h for raw material, obtain compound 15h, white solid (86%) 1HNMR (500MHz according to the method for embodiment 8, 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)
With compound 15h for raw material, obtain compound 16h, white solid (93%) according to the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 7.66 (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
Malonic acid pair-(2,4,6-trichlorophenyl) ester (17)
1,3-malonic acid (40g, 0.38mol) is dissolved in 1000mlDMF, 2,4,6-trichlorophenol, 2,4,6,-T (151g are added under room temperature, 0.76mol), finish, drip phosphorus oxychloride (116.5g in this temperature, 0.76mol), it is ensured that strictly anhydrous, finish, reacting 7-8h at 120 DEG C, DMF is steamed after terminating by reaction, acetic acid ethyl dissolution system, saturated common salt is washed, and anhydrous magnesium sulfate is dried overnight.Filter, rotation is evaporated off ethyl acetate, residue petroleum ether: ethyl acetate=8:1 crosses silicagel column, obtain compound (17) (122g, 64%) white solid 1HNMR (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 ester (30g, 0.25mol) under room temperature, is warming up to system backflow, and after 2.5h, reaction terminates.Being steamed by dry toluene, acetic acid ethyl dissolution system, saturated common salt is washed, and anhydrous magnesium sulfate is dried overnight.Filtering, rotation is evaporated off ethyl acetate, and residue petroleum ether: ethyl acetate=10:1 crosses silicagel column obtains compound 18 (25g, 64.1%) white solid.1HNMR(500MHz,CDCl3)δ5.28(s,1H),3.82(s,3H),2.47(s,3H).
Embodiment 170
4,6-dimethoxy-2-methyinicotinate (19)
Compound 18 (22g, 0.12mol) is dissolved in 400ml dry DMF, adds Anhydrous potassium carbonate (76g, 0.55mol), is added dropwise over iodomethane (37.5g, 0.26mol), finishes, be warming up to 100 DEG C, keeps 3h, and reaction terminates.Dry DMF being steamed, acetic acid ethyl dissolution system, saturated common salt is washed, and anhydrous magnesium sulfate is dried overnight.Filtering, rotation is evaporated off ethyl acetate, and residue petroleum ether: ethyl acetate=10:1 crosses silicagel column obtains compound 19 (20g, 79%) white solid.1HNMR(500MHz,CDCl3)δ6.42(s,1H),3.96(s,6H),3.88(s,3H),2.60(s,3H).
Embodiment 171
2-bromomethyl-4,6-dimethoxy-methyl nicotinate (20)
With compound 19 for raw material, compound 20 is obtained 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 methyl nicotinate (21)
With compound 20 for raw material, obtain compound 21, white solid (65%) according to the method for embodiment 4, white solid 1HNMR (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 methyl nicotinate (22a)
With benzaldehyde and compound 21 for raw material, obtain this compound (22a), white solid (87%) .1HNMR (500MHz with the method that embodiment 5 is similar, 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 methyl nicotinate (23a)
With compound 22a for raw material, it is obtained by reacting compound 23a, white solid (92%) by the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 7.52 (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-methyl nicotinate (24a)
With compound 23a for raw material, it is obtained by reacting compound 24a, white solid (53%) by the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 7.68 (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)
With compound 24a for raw material, it is obtained by reacting compound 25a, white solid (89%) by the method for embodiment 8.1HNMR (500MHz, CDCl3) δ 7.62 (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-pyridin-4-alcohol (26a)
With compound 25a for raw material, it is obtained by reacting compound 26a, white solid (93%) by the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.54 (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)-methyl nicotinate (22b)
With 2-pyridine carboxaldehyde and compound 21 for raw material, obtain this compound 22b, white solid (78%) 1HNMR (500MHz, CDCl3) δ 8.42 (s with the method that embodiment 5 is similar, 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)-methyl nicotinate (23b)
With compound 22b for raw material, it is obtained by reacting compound 23b, white solid (92%) by the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 8.46 (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)-methyl nicotinate (24b)
With compound 23b for raw material, it is obtained by reacting compound 24b, white solid (53%) by the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 8.54 (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)
With compound 24b for raw material, it is obtained by reacting compound 25b, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.42 (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)
With compound 25b for raw material, it is obtained by reacting compound 26b, white solid (87%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 8.46 (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)-methyl nicotinate (22c)
With 3-pyridine carboxaldehyde and compound 21 for raw material, obtain this compound, white solid (82%) 1HNMR (500MHz, CDCl3) δ 8.52 (d with the method that embodiment 5 is similar, 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)-methyl nicotinate (23c)
With compound 22c for raw material, it is obtained by reacting compound 23c, white solid (90%) by the method that embodiment 6 is similar.1HNMR(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)-methyl nicotinate (24c)
With compound 23c for raw material, it is obtained by reacting compound 24c, white solid (53%) by the method that embodiment 7 is similar.1HNMR (500MHz, CDCl3) δ 8.54 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)
With compound 24c for raw material, it is obtained by reacting compound 25c, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.51 (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)
With compound 25c for raw material, it is obtained by reacting compound 26c, white solid (96%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 8.59 (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)-methyl nicotinate (22d)
With 4-pyridine carboxaldehyde and compound 21 for raw material, obtain this compound 22d, white solid (82%) 1HNMR (500MHz with the method that embodiment 5 is similar, 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)-methyl nicotinate (23d)
With compound 22d for raw material, it is obtained by reacting compound 23d, white solid (90%) by the method that embodiment 6 is similar.1HNMR(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)-methyl nicotinate (24d)
With compound 23d for raw material, it is obtained by reacting compound 24d, white solid (44%) by the method that embodiment 7 is similar.1HNMR (500MHz, CDCl3) δ 8.64 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)
With compound 24d for raw material, it is obtained by reacting compound 25d, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.61 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)
With compound 25d for raw material, it is obtained by reacting compound 26d, white solid (90%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 8.64 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-furan-2-base-vinyl)-4,6-dimethoxy-methyl nicotinate (22e)
With 2 furan carboxyaldehyde and compound 21 for raw material, obtain this compound 22e, white solid (78%) 1HNMR (500MHz, CDCl3) δ 7.63 (t with the method that embodiment 5 is similar, 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-furan-2-base-vinyl)-4-hydroxyl-6-methoxynicotinate (23e)
With compound 22e for raw material, it is obtained by reacting compound 23e, white solid (53%) 1HNMR (500MHz, CDCl3) δ 7.66 (s by the method that embodiment 7 is similar, 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-furan-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-methyl nicotinate (24e)
With compound 23e for raw material, it is obtained by reacting compound 24e, white solid (53%) 1HNMR (500MHz by the method that embodiment is similar, 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-furan-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid
(25e)
With compound 24e for raw material, it is obtained by reacting compound 25e, white solid (89%) by the method that embodiment 8 is similar.1HNMR(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-furan-2-base-vinyl)-2-methoxyl group-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol (26e)
With compound 25e for raw material, it is obtained by reacting compound 26e, white solid (93%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 7.64 (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's-2-base)-vinyl]-methyl nicotinate (22f)
With 2-pyrrole aldehyde and compound 21 for raw material, obtain this compound 22f, white solid (78%) 1HNMR (500MHz with the method that embodiment 5 is similar, 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's-2-base)-vinyl]-methyl nicotinate (23f)
With compound 22f for raw material, it is obtained by reacting compound 23f, white solid (53%) 1HNMR (500MHz by the method that embodiment 7 is similar, 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's-2-base)-vinyl]-methyl nicotinate (24f)
With compound 23f for raw material, it is obtained by reacting compound 24f, white solid (72%) 1HNMR (500MHz by the method that embodiment is similar, 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's-2-base)-vinyl]-nicotinic acid (25f)
With compound 24f for raw material, it is obtained by reacting compound 25f, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 9.66 (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's-2-base)-vinyl]-pyridine-4-alcohol (26f)
With compound 25f for raw material, it is obtained by reacting compound 26f, white solid (93%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 9.66 (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) methyl nicotinate (22g)
With 2-thiazole carboxaldehyde and compound 21 for raw material, obtain this compound 22g, white solid (78%) 1HNMR (500MHz with the method that embodiment 5 is similar, 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)-methyl nicotinate (23g)
With compound 22g for raw material, it is obtained by reacting compound 23g, white solid (53%) 1HNMR (500MHz by the method that embodiment 6 is similar, 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-methyl nicotinate (24g)
With compound 23g for raw material, it is obtained by reacting compound 24g, white solid (53%) 1HNMR (500MHz by the method that embodiment 7 is similar, 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)
With compound 24g for raw material, it is obtained by reacting compound 25g, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 7.87 (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)
With compound 25g for raw material, it is obtained by reacting compound 26g, white solid (93%) by the method that embodiment 9 is similar.1HNMR(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-base)-vinyl]-4,6-dimethoxy-methyl nicotinate (22h)
With 2-imidazole formaldehyde and compound 21 for raw material, obtain this compound 22h, white solid (78%) 1HNMR (500MHz with the method that embodiment 5 is similar, 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-base) vinyl]-6-methoxynicotinate (23h)
With compound 22h for raw material, it is obtained by reacting compound 23h, white solid (53%) 1HNMR (500MHz, CDCl3) δ 7.78 (s by the method that embodiment 7 is similar, 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-base)-vinyl]-6-methoxyl group-5-(3-methyl but-2-ene base)-methyl nicotinate (24h)
With compound 23h for raw material, it is obtained by reacting compound 24h, white solid (53%) 1HNMR (500MHz by the method that embodiment 8 is similar, 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-base)-vinyl]-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid (25h)
With compound 24h for raw material, it is obtained by reacting compound 25h, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.24 (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-base)-vinyl]-2-methoxyl group-3-(3-methyl but-2-ene base)-pyridine-4-alcohol (26h)
With compound 25h for raw material, it is obtained by reacting compound 26h, white solid (72%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 7.71 (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-base)-vinyl]-methyl nicotinate (22i)
With 5-methoxypyridine-2-formaldehyde and compound 21 for raw material, obtain this compound 22i, white solid (87%) 1HNMR (500MHz with the method that embodiment 5 is similar, 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-base)-vinyl]-nicotinic acid methyl ester (23i)
With compound 22i for raw material, it is obtained by reacting compound 23i, white solid (71%) 1HNMR (500MHz by the method that embodiment 7 is similar, 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-base) vinyl]-5-(3-methyl but-2-ene base) methyl nicotinate
With compound 23i for raw material, it is obtained by reacting compound 24i, white solid (64%) 1HNMR (500MHz by the method that embodiment 8 is similar, 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-base) vinyl]-5-(3-methyl but-2-ene base) nicotinic acid
With compound 24i for raw material, it is obtained by reacting compound 25i, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.02 (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-base)-vinyl]-3-(3-methyl but-2-ene base)-pyridine-4-alcohol
With compound 25i for raw material, it is obtained by reacting compound 26i, white solid (93%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 8.12 (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
4,6-dimethoxy-2-phenylene-ethynylene-methyl nicotinate (22 ' a)
Compound 21 ' a (77%) 1HNMR (500MHz, Chloroform) δ 7.71 7.59 (m, 2H) is obtained for raw material according to the method for embodiment 120 with 22a, 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 methyl nicotinate (27a)
With compound 22 ' a for raw material, it is obtained by reacting compound 27a, white solid (80%) 1HNMR (500MHz, CDCl3) δ 7.54 7.41 (m by the method for 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 methyl nicotinate (28a)
With compound 27a for raw material, it is obtained by reacting compound 28a (91%) by the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 7.53 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-methyl nicotinate (29a)
With compound 28a for raw material, it is obtained by reacting compound 29a, white solid (53%) by the method for embodiment 7.1HNMR(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)
With compound 29a for raw material, it is obtained by reacting compound 30a, white solid (89%) by the method for embodiment 8.1HNMR (500MHz, CDCl3) δ 7.81 (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-pyridin-4-alcohol (31a)
With compound 30a for raw material, it is obtained by reacting compound 31a, white solid (87%) by the method for embodiment 9.1HNMR (500MHz, CDCl3) δ 7.60 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
4,6-dimethoxy-2-pyridine-2-ethyl-acetylene base-methyl nicotinate (22 ' b)
Compound 21 ' b (87%) 1HNMR (500MHz, Chloroform) δ 8.04 (s, 1H) is obtained for raw material according to the method for embodiment 120 with 22b, 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)-methyl nicotinate (27b)
With 22 ' b for raw material, obtain this compound 27b, white solid (78%) 1HNMR (500MHz, CDCl3) δ 8.45 (s with the method that embodiment 121 is similar, 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)-methyl nicotinate (28b)
With compound 27b for raw material, it is obtained by reacting compound 28b, white solid (92%) by the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 8.43 (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)-methyl nicotinate (29b)
With compound 28b for raw material, it is obtained by reacting compound 29b, white solid (46%) by the method for embodiment 7.1HNMR (500MHz, CDCl3) δ 8.80 (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)
With compound 29b for raw material, it is obtained by reacting compound 305b, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.37 (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)
With compound 25b for raw material, it is obtained by reacting compound 26b, white solid (91%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 8.44 (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
4,6-dimethoxy-2-pyridin-3-yl acetenyl-methyl nicotinate (22 ' c)
Compound 22 ' c (78%) 1HNMR (500MHz, Chloroform) δ 8.04 (s, 1H) is obtained for raw material according to the method for embodiment 120 with 22c, 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)-methyl nicotinate (27c)
With 22 ' c for raw material, obtain this compound, white solid (82%) 1HNMR (500MHz with the method that embodiment 121 is similar, 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)-methyl nicotinate (28c)
With compound 27c for raw material, it is obtained by reacting compound 28c, white solid (88%) by the method that embodiment 6 is similar.1HNMR(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)-methyl nicotinate (29c)
With compound 28c for raw material, it is obtained by reacting compound 29c, white solid (67%) by the method that embodiment 7 is similar.1HNMR (500MHz, CDCl3) δ 8.57 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)
With compound 29c for raw material, it is obtained by reacting compound 30c, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.52 (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)
With compound 30c for raw material, it is obtained by reacting compound 31c, white solid (90%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 8.58-8.42 (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
4,6-dimethoxy-2-pyridin-4-yl acetenyl-methyl nicotinate (22 ' d)
Compound 22 ' d (77%) 1HNMR (500MHz is obtained for raw material according to the method for embodiment 120 with 22d, 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)-methyl nicotinate (27d)
With 22 ' d for raw material, obtain this compound 27d, white solid (82%) 1HNMR (500MHz with the method that embodiment 121 is similar, 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)-methyl nicotinate (28d)
With compound 27d for raw material, it is obtained by reacting compound 28d, white solid (92%) by the method that embodiment 6 is similar.1HNMR(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)-methyl nicotinate (29d)
With compound 28d for raw material, it is obtained by reacting compound 29d, white solid (92%) by the method that embodiment 7 is similar.1HNMR (500MHz, CDCl3) δ 8.66 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)
With compound 29d for raw material, it is obtained by reacting compound 30d, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.69 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)
With compound 30d for raw material, it is obtained by reacting compound 31d, white solid (91%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 8.63 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-furan-2-ethyl-acetylene base-4-2,6-dimethoxy-methyl nicotinate (22 ' e)
Compound 22 ' e (86%) 1HNMR (500MHz, Chloroform) δ 7.64 (s, 1H) is obtained for raw material according to the method for embodiment 120 with 22e, 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-furan-2-base-vinyl)-4,6-dimethoxy-methyl nicotinate (27e)
With 22 ' e for raw material, obtain this compound 27e, white solid (78%) 1HNMR (500MHz with the method that embodiment 121 is similar, 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-furan-2-base-vinyl)-4-hydroxyl-6-methoxynicotinate (28e)
With compound 27e for raw material, it is obtained by reacting compound 28e, white solid (77%) 1HNMR (500MHz, CDCl3) δ 7.49 (s by the method that embodiment 7 is similar, 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-furan-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-methyl nicotinate (29e)
With compound 28e for raw material, it is obtained by reacting compound 29e, white solid (49%) 1HNMR (500MHz by the method that embodiment is similar, 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-furan-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid (30e)
With compound 29e for raw material, it is obtained by reacting compound 30e, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.88 (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-furan-2-base-vinyl)-2-methoxyl group-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol (31e)
With compound 30e for raw material, it is obtained by reacting compound 31e, white solid (93%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 7.66 (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's-2-ethyl-acetylene base-4-2,6-dimethoxy-methyl nicotinate (22 ' f)
Compound 22 ' f (85%) 1HNMR (500MHz, Chloroform) δ 7.04 (s, 1H) is obtained for raw material according to the method for embodiment 120 with 22f, 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's-2-base)-vinyl]-methyl nicotinate (27f)
With 22 ' f for raw material, obtain this compound 27f, white solid (78%) 1HNMR (500MHz with the method that embodiment 121 is similar, 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's-2-base)-vinyl]-methyl nicotinate (28f)
With compound 27f for raw material, it is obtained by reacting compound 28f, white solid (87%) 1HNMR (500MHz, CDCl3) δ 9.64 (s by the method that embodiment 7 is similar, 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's-2-base)-vinyl]-methyl nicotinate (29f)
With compound 28f for raw material, it is obtained by reacting compound 29f, white solid (59%) 1HNMR (500MHz by the method that embodiment is similar, 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's-2-base)-vinyl]-nicotinic acid (30f)
With compound 29f for raw material, it is obtained by reacting compound 30f, white solid (87%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 9.65 (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's-2-base)-vinyl]-pyridine-4-alcohol (31f)
With compound 30f for raw material, it is obtained by reacting compound 31f, white solid (96%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 9.66 (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
4,6-dimethoxy-2-thiazol-2-yl acetenyl-methyl nicotinate (22 ' g)
Compound 22 ' g (75%) 1HNMR (500MHz is obtained for raw material according to the method for embodiment 120 with 22g, 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) methyl nicotinate (27g)
With 22 ' g for raw material, obtain this compound 22g, white solid (78%) 1HNMR (500MHz with the method that embodiment 121 is similar, 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)-methyl nicotinate (28g)
With compound 27g for raw material, it is obtained by reacting compound 28g, white solid (86%) 1HNMR (500MHz, CDCl3) δ 7.75 (d by the method that embodiment 6 is similar, 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)-methyl nicotinate (29g)
With compound 28g for raw material, it is obtained by reacting compound 29g, white solid (53%) 1HNMR (500MHz by the method that embodiment 7 is similar, 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)
With compound 30g for raw material, it is obtained by reacting compound 30g, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.54 (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)
With compound 30g for raw material, it is obtained by reacting compound 31g, white solid (95%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 7.74 (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)-4,6-dimethoxy-methyl nicotinate (22 ' h)
Compound 21 ' h. (76%) 1HNMR (500MHz, Chloroform) δ 7.20 (s, 1H) is obtained for raw material according to the method for embodiment 120 with 22h, 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-base)-vinyl]-4,6-dimethoxy-methyl nicotinate (27h)
With 22 ' h for raw material, obtain this compound 27h, white solid (78%) 1HNMR (500MHz with the method that embodiment 121 is similar, 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-base) vinyl]-6-methoxynicotinate (28h)
With compound 27h for raw material, it is obtained by reacting compound 23h, white solid (78%) 1HNMR (500MHz, CDCl3) δ 9.98 (s by the method that embodiment 7 is similar, 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-base)-vinyl]-6-methoxyl group-5-(3-methyl but-2-ene base)-methyl nicotinate (29h)
With compound 28h for raw material, it is obtained by reacting compound 29h, white solid (53%) 1HNMR (500MHz by the method that embodiment 8 is similar, 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-base)-vinyl]-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid (30h)
With compound 29h for raw material, it is obtained by reacting compound 30h, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.25 (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-base)-vinyl]-2-methoxyl group-3-(3-methyl but-2-ene base)-pyridine-4-alcohol (31h)
With compound 30h for raw material, it is obtained by reacting compound 31h, white solid (96%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 7.65 (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)-4,6-dimethoxy-methyl nicotinate (22 ' i)
Compound 21 ' i (79%) 1HNMR (500MHz, Chloroform) δ 8.19 (s, 1H) is obtained for raw material according to the method for embodiment 120 with 22i, 7.38 (s, 2H), 6.51 (s, 1H), 3.92 (s, 12H).
Embodiment 267
(Z)-4,6-dimethoxy-2-[2-(5-methoxypyridine-2-base)-vinyl]-methyl nicotinate (27i)
With 22 ' i for raw material, obtain this compound 27i, white solid (78%) 1HNMR (500MHz, CDCl3) δ 8.03 (s with the method that embodiment 121 is similar, 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-base)-vinyl]-nicotinic acid methyl ester (28i)
With compound 22i for raw material, it is obtained by reacting compound 28i, white solid (79%) 1HNMR (500MHz by the method that embodiment 7 is similar, 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-base) vinyl]-5-(3-methyl but-2-ene base) methyl nicotinate (29i)
With compound 28i for raw material, it is obtained by reacting compound 29i, white solid (58%) 1HNMR (500MHz by the method that embodiment 8 is similar, 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-base) vinyl]-5-(3-methyl but-2-ene base) nicotinic acid (30i)
With compound 29i for raw material, it is obtained by reacting compound 30i, white solid (89%) by the method that embodiment 8 is similar.1HNMR (500MHz, CDCl3) δ 8.13 (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-base)-vinyl]-3-(3-methyl but-2-ene base)-pyridine-4-alcohol (31i)
With compound 30i for raw material, it is obtained by reacting compound 31i, white solid (93%) by the method that embodiment 9 is similar.1HNMR (500MHz, CDCl3) δ 7.96 (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)
Metallic sodium (3.1g, 0.134mol) it is dissolved in absolute methanol (200ml), methyl acetoacetate (12.0g is added in room temperature, 0.103mol), with Methyl crotonate (12.4g, 0.124mol), add, back flow reaction 6h, reaction is finished, and steams major part methanol, residue joins frozen water (200ml), being extracted with ethyl acetate (3X50ml), water layer regulates pH less than 2 with the dilute hydrochloric acid of 15%, then is extracted with ethyl acetate (3X50ml).Merging organic layer, organic layer saturated common salt is washed, and anhydrous MgSO4 dries.Filtering, solvent evaporated, residue petrol ether/ethyl acetate recrystallization obtains white solid (13.2g, 70%).1HNMR (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 (33) of 2,4-dihydroxy-3-
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, at room temperature react 12h.Reaction is finished, and reactant liquor is poured in frozen water, precipitates out a large amount of white solid, filters, filter cake massive laundering, dry.Gained solid is crossed silicagel column by petrol ether/ethyl acetate further and is obtained relatively pure products, white solid (5.6g, 40%).1HNMR(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 (34) of 2,4-dimethoxy-3-
With compound 33 for raw material, obtain product, white solid (95%) according to the method for embodiment 2.1HNMR(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 (35) of 2,4-dimethoxy-3-
With compound 34 for raw material, obtain product, white solid (82%) according to the method for embodiment 3.1HNMR(400MHz,CDCl3):3.90(s,3H),3.94(s,3H),3.96(s,3H),4.53(s,2H),6.73(s,1H).
Embodiment 276
2,4-dimethoxy-3-bromo-6-diethyl phosphite methyl toluate (36)
With compound 35 for raw material, obtain product, white solid (86%) according to the method for embodiment 4.1HNMR(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) essence of Niobe (37a)
By compound 36 (5g, 0.012mol) it is dissolved in dry toluene, adds isopentene group amine, three (dibenzalacetone) two palladium, potassium tert-butoxide, heating, to 110 DEG C, keeps temperature 16h, after reaction terminates, toluene is steamed, acetic acid ethyl dissolution (3X50ml), saturated aqueous common salt washes twice, and water layer is extracted with ethyl acetate (3X50ml) again.Merging organic layer, anhydrous MgSO4 dries.Filtering, solvent evaporated, residue petrol ether/ethyl acetate recrystallization obtains white solid (3.8g, 76%).1HNMR (500MHz, CDCl3) δ 6.62 (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-essence of Niobe (38a)
With compound 37a for raw material, obtain product, white solid (81%) according to the method for embodiment 5.1HNMR (500MHz, CDCl3) δ 7.68 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-essence of Niobe (39a)
With compound 38a for raw material, obtain product, white solid (74%) according to the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 7.66 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-benzoic acid (40a)
With compound 39a for raw material, obtain product, white solid (69%) according to the method for embodiment 8.1HNMR (500MHz, CDCl3) δ 7.71 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-butylamino) essence of Niobe (37b)
With isoamylamine for raw material, obtain product, white solid (70%) according to the method for embodiment 277.1HNMR (500MHz, CDCl3) δ 6.64 (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-butylamino)-6-styryl-essence of Niobe (38b)
With compound 37b for raw material, obtain product, white solid (71%) according to the method for embodiment 5.1HNMR(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-butylamino)-6-styryl-essence of Niobe (39b)
With compound 38b for raw material, obtain product, white solid (73%) according to the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 7.68 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-butylamino)-6-styryl-benzoic acid (40b)
With compound 39b for raw material, obtain product, white solid (84%) according to the method for embodiment 8.1HNMR (500MHz, CDCl3) δ 7.60 (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)
With n-butyl alcohol for raw material, obtain product, white solid (70%) according to the method for embodiment 277.1HNMR (500MHz, CDCl3) δ 6.64 (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-butylamino)-6-styryl-essence of Niobe (38b)
With compound 37b for raw material, obtain product, white solid (71%) according to the method for embodiment 5.1HNMR(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-butylamino)-6-styryl-essence of Niobe (39b)
With compound 38b for raw material, obtain product, white solid (73%) according to the method for embodiment 6.1HNMR (500MHz, CDCl3) δ 7.68 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-butylamino)-6-styryl-benzoic acid (40b)
With compound 39b for raw material, obtain product, white solid (84%) according to the method for embodiment 8.1HNMR (500MHz, CDCl3) δ 7.60 (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 measures
Mdck cell inoculates 96 well culture plates, is placed in 5%CO2, 37C cultivates 24 hours.Mdck cell adds influenza virus (A/H1N1, A/H3N2 or B/13/79 type) about 100TCID50, and 37 DEG C of absorption hypsokinesis in 2 hours is prevented or cure a disease venom, is separately added into the maintenance medium of different dilution the compounds of this invention or positive control drug ribavirin.Set the virus control of not dosing and the cell controls of virus-free infection simultaneously, 37C cultivates and observes each group of cytopathy degree (CPE) (about 36 hours) when virus control group lesion degree (CPE) reaches 4+, calculating each sample resisiting influenza virus half-inhibition concentration (IC50), result is referring to table 1.
Experimental example 2 anti-COxsackie (CoxaskiEs) virus activity measures
VEro cell kind 96 well culture plate, 24 hours postoperative infection virus (cells of coxsackie B 3 virus) about 100TCID50, adsorb 2 hours, abandon virus liquid, add the maintenance medium of the compounds of this invention sample containing variable concentrations and positive control drug ribavirin (RBV), set the virus control of not dosing and the cell controls of virus-free infection simultaneously, each group of cytopathy degree (CPE) is observed when virus control group lesion degree (CPE) reaches 4+, calculate the half-inhibition concentration (IC50) of samples for viral respectively by REEd-MuEnch method, result lists table 2 in.
Experimental example 3 anti AIDS virus (HIV) determination of activity
MT-4 cell washs 2 times by culture medium after infecting 1.5h with the 37 DEG C of absorption of 100TCID50HIV-1 III B virus, is configured to 2 × 10 with culture fluid5Cell mL-1,100 μ L are inoculated in 96 porocyte culture plates, add the medicinal liquid of the variable concentrations of 3 times of dilutions or the positive drug AZT medicinal liquid of 4 times of dilutions respectively simultaneously, and each concentration repeats 2 holes, if cell controls group.Put in 37C, 5%CO2 and saturated humidity incubator and cultivate, after dosing 96h, suct clear 100 μ L, with the content of kit measurement P24 antigen, calculate IC50.The activity of described compound AntiHIV1 RT activity is in Table 2.
Experimental example 4 anti-hepatitis virus (HBV) determination of activity
After HepG2.2.15 Tissue Culture Flask covers with cell, through digestion, being configured to every milliliter of 200,000 cells, inoculate 96 well culture plates, every hole 100ml, 37 DEG C of 5%CO2 cultivate 24 hours, and cell is tested after growing up to monolayer.After medicine culture fluid is configured to variable concentrations, adding 96 porocyte culture plates, 37 DEG C of 5%CO2 cultivate, and cell is cultured to the 3rd day and observes with inverted microscope, with cytopathy (CPE) for cytotoxicity index.Record cytopathy, destroying completely is 4；75% is 3；50% is 2；25% is 1；Anosis become 0.The poisonous concentration of half (TC50) and maximal non-toxic concentration (TC0) is calculated by Reed-Muench method.Plate inner cell DNA rapid extraction test kit in a small amount extracts DNA in cell, add primer, by the level (GAPDHCt value) of the level (HVBCt value) of DNA in qPCR test kit and iQ5 quantitative PCR apparatus detection by quantitative cell and cell internal reference gene GAPDH.Inhibition percentage is calculated by following equation.((HBVCt cell controls-HBVCt medicine group)/(GAPDHCt cell controls-GAPDHCt medicine group) × 100% calculates (EC50) by Reed-Muench method to suppress percentage %=1/2^.The selection result is listed in table 3
Experimental example 5 anti-hepatitis C virus (HCV) determination of activity
Huh7.5 cell is with 3 × 104The density of cells/cm2 is inoculated in 96 orifice plates, after cultivating 24h, with HCV vial supernatant with 45IU/cell infection cell, is simultaneously introduced medicinal liquid or solvent control processes.After cultivating 72h, culture medium is abandoned in suction, extracts total serum IgE in cell, HCVRNA expression one-stepreal-timeRT-PCRkit detection by quantitative with RNeasyMiniKit, with calculating the medicine suppression ratio to HCV, and calculate the poisonous concentration EC50 of half by Reed-Muench method.The activity of described compound HCV-Ab IgG is in Table 3.

Claims (6)

1. one group of compound or its pharmaceutically acceptable salt, it is:
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-benzoic acid；
(E)-2-hydroxyl-6-[2-(1H-imidazoles-2-base)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-2-hydroxyl-6-[2-(1H-imidazoles-2-base)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles's-2-base)-vinyl]-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles's-2-base)-vinyl]-benzoic acid；
(E)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-6-(2-furan-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-6-(2-furan-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-6-[2-(3,4-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-6-[2-(3,4-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-6-[2-(2,4-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-6-[2-(2,4-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(6-methoxypyridine-3-base)-vinyl]-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(6-methoxypyridine-3-base)-vinyl]-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-6-[2-(4,6-dimethoxy-pyridine-3-base)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-6-[2-(4,6-dimethoxy-pyridine-3-base)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxypyridine-4-base)-vinyl]-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxypyridine-4-base)-vinyl]-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-6-[2-(2,5-dimethoxy-pyridine-4-base)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-6-[2-(2,5-dimethoxy-pyridine-4-base)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles's-3-base) vinyl] essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles's-3-base) vinyl] benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-1H-pyrroles's-3-base)-vinyl]-3-(3-methyl-but-2-ene base-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-1H-pyrroles's-3-base)-vinyl]-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-6-(2-furan-3-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-6-(2-furan-3-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group furan-3-base)-vinyl]-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group furan-3-base)-vinyl]-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-2-hydroxyl-6-[2-(2H-imidazol-4 yl)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-2-hydroxyl-6-[2-(2H-imidazol-4 yl)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-2H-imidazol-4 yl)-vinyl]-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(5-methoxyl group-2H-imidazol-4 yl)-vinyl]-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazole-5-base-vinyl)-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazole-5-base-vinyl)-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group-thiazole-5-base)-vinyl]-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(4-methoxyl group-thiazole-5-base)-vinyl]-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-5-base-vinyl)-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-5-base-vinyl)-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxyl group-oxazole-5-base)-vinyl]-3-(3-methyl-but-2-ene base)-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-6-[2-(2-methoxyl group-oxazole-5-base)-vinyl]-3-(3-methyl-but-2-ene base)-benzoic acid；
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-styryl-methyl nicotinate；
(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)-methyl nicotinate；
(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)-methyl nicotinate；
(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)-methyl nicotinate；
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridin-4-yl-vinyl)-nicotinic acid；
(E)-2-(2-furan-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-methyl nicotinate；
(E)-2-(2-furan-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's-2-base)-vinyl]-methyl nicotinate；
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-[2-(1H-pyrroles's-2-base)-vinyl]-nicotinic acid；
(E)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-thiazol-2-yl-vinyl-methyl nicotinate；
(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-base)-vinyl]-6-methoxyl group-5-(3-methyl-but-2-ene base)-methyl nicotinate；
(E)-4-hydroxyl-2-[2-(1H-imidazoles-2-base)-vinyl]-6-methoxyl group-5-(3-methyl-but-2-ene base)-nicotinic acid；
(E)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-base) vinyl]-5-(3-methyl-but-2-ene base) methyl nicotinate；
(E)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-base) 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-base) 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's-2-base)-vinyl]-phenol；
(E)-5-(2-biphenyl-4-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol；
(E)-5-(2-furan-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-base)-vinyl]-2-(3-methyl-but-2-ene base)-phenol；
(E)-5-(2-(4,6-dimethoxy-pyridine-3-base) vinyl]-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol；
(E)-3-methoxyl group-5-[2-(2-methoxypyridine-4-base)-vinyl]-2-(3-methyl-but-2-ene base)-phenol；
(E)-5-(2-(2,5-dimethoxy-pyridine-4-base) 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's-3-base)-vinyl]-phenol；
(E)-3-methoxyl group-5-[2-(5-methoxyl group-1H-pyrroles's-3-base)-vinyl]-2-(3-methyl-but-2-ene base)-phenol；
(E)-5-(2-furan-3-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol；
(E)-3-methoxyl group-5-[2-(4-methoxyl group furan-3-base)-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-base)-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-base)-vinyl]-2-(3-methyl but-2-ene base)-phenol；
(E)-2-methoxyl group-3-(3-methyl-but-2-ene base)-6-Styryl-pyridin-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-furan-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's-2-base)-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-base)-vinyl]-2-methoxyl group-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol；
(E)-2-methoxyl group-6-[2-(5-methoxypyridine-2-base)-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)-essence of Niobe；
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-thiazol-2-yl-vinyl)-benzoic acid；
(Z)-2-hydroxyl-6-[2-(1H-imidazoles-2-base)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(Z)-2-hydroxyl-6-[2-(1H-imidazoles-2-base)-vinyl]-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-essence of Niobe；
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-(2-oxazole-2-base-vinyl)-benzoic acid；
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles's-2-base)-vinyl]-essence of Niobe；
(Z)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-6-[2-(1H-pyrroles's-2-base)-vinyl]-benzoic acid；
(Z)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(Z)-2-hydroxyl-4-6-(2-biphenyl-4-base-vinyl)-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(Z)-6-(2-furan-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(Z)-6-(2-furan-2-base-vinyl)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(Z)-6-[2-(3,4-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(Z)-6-[2-(3,4-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(Z)-6-[2-(2,4-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-essence of Niobe；
(Z)-6-[2-(2,4-dihydroxy-phenyl)-vinyl]-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base)-benzoic acid；
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-styryl-methyl nicotinate；
(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)-methyl nicotinate；
(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)-methyl nicotinate；
(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)-methyl nicotinate；
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-pyridin-4-yl-vinyl)-nicotinic acid；
(Z)-2-(2-furan-2-base-vinyl)-4-hydroxyl-6-methoxyl group-5-(3-methyl but-2-ene base)-methyl nicotinate；
(Z)-2-(2-furan-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's-2-base)-vinyl]-methyl nicotinate；
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-[2-(1H-pyrroles's-2-base)-vinyl]-nicotinic acid；
(Z)-4-hydroxyl-6-methoxyl group-5-(3-methyl-but-2-ene base)-2-(2-thiazol-2-yl-vinyl-methyl nicotinate；
(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-base)-vinyl]-6-methoxyl group-5-(3-methyl-but-2-ene base)-methyl nicotinate；
(Z)-4-hydroxyl-2-[2-(1H-imidazoles-2-base)-vinyl]-6-methoxyl group-5-(3-methyl but-2-ene base)-nicotinic acid；
(Z)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-base) vinyl]-5-(3-methyl-but-2-ene base) methyl nicotinate；
(Z)-4-hydroxyl-6-methoxyl group-2-[2-(5-methoxypyridine-2-base) 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-base) 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's-2-base)-vinyl]-phenol；
(Z)-5-(2-biphenyl-4-base-vinyl)-3-methoxyl group-2-(3-methyl-but-2-ene base)-phenol；
(Z)-5-(2-furan-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-pyridin-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-furan-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's-2-base)-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-base)-vinyl]-2-methoxyl group-3-(3-methyl-but-2-ene base)-pyridine-4-alcohol；
(Z)-2-methoxyl group-6-[2-(5-methoxypyridine-2-base)-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-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene base amino)-6-styryl-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-3-(3-Methyl-butylamino)-6-styryl-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-3-(3-Methyl-butylamino)-6-styryl-benzoic acid；
(E)-3-butoxy-2-hydroxyl-4-methoxyl group-6-styryl-essence of Niobe；
(E)-3-butoxy-2-hydroxyl-4-methoxyl group-6-styryl-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-butoxy)-6-styryl-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-butoxy)-6-styryl-benzoic acid；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene oxygen base)-6-styryl-essence of Niobe；
(E)-2-hydroxyl-4-methoxyl group-3-(3-methyl-but-2-ene oxygen base)-6-styryl-benzoic acid.
2. compound described in claim 1 or the application in preparing viral infection resisting medicine of its pharmaceutically acceptable salt.
3. applying as claimed in claim 2, wherein, described virus includes influenza virus, cells of coxsackie B 3 virus, HIV (human immunodeficiency virus), hepatitis B virus and hepatitis C virus.
4. an antiviral medicinal composition, its active component includes the compound described in claim 1 or its pharmaceutically acceptable salt.
5. pharmaceutical composition as claimed in claim 4, wherein, compound or its pharmaceutically acceptable salt weight content in this pharmaceutical composition described in claim 1 are 0.1%-99.5%.
6. pharmaceutical composition as claimed in claim 5, wherein, compound or its pharmaceutically acceptable salt weight content in this pharmaceutical composition described in claim 1 are 0.5%-99.5%.
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