CN109896943A - A kind of chemical preparation process of cajanin and its analogue - Google Patents
A kind of chemical preparation process of cajanin and its analogue Download PDFInfo
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Abstract
The invention belongs to synthesize the field of cajanin, the chemical preparation process of a kind of cajanin and its analogue is disclosed.This method is with 2- bromo- 4,6- dimethoxy benzaldehyde and substituted phenylethylene are starting material, cajanin and its analogue are chemically synthetically prepared by 6 steps, and the analogue of cajanin can also be prepared by carrying out simple transformation alkylating reagent or increase step of hydrogenation to the synthetic method, this method has step brief, the advantages that raw material is cheap and easy to get, and total recovery is high.The inventive method has universal applicability to the synthesis of cajanin analog.
Description
Technical field
The invention belongs to synthesize the field of cajanin, the in particular to chemical preparation of a kind of cajanin and its analogue
Method.
Background technique
Cajanin belongs to stilbene compound, and (extraction and purification process of cajanin and its antibacterial activity are ground in Kong Yu cajan leaf
Study carefully Northeast Forestry University, 2008.), cajanin and the like has various active, has anti-inflammatory and analgesic effect, and effect is better than water
Poplar acid；Anti-tumor aspect, cajanin all show preferable effect, active and toxicity suitable with taxol to kinds of tumors
Smaller (CN101569654A, 2009.11.4).In addition, cajanin also has antiviral activity such as anti-HSV-1 and HSV-2
The derivative of active (referring to CN101485649A, 2009.7.22), domestic Li Zhuorong seminar research discovery cajanin can be effective
Inhibit Hepatitis C Virus (Journal of Medicinal Chemistry, 59 (22), 10268-10284；2016).Separately
Outside, cajanin derivative also has the activity and inflammation inhibitory activity (European Journal of of preferable anti-positive bacterium
Medicinal Chemistry,100,235-245；2015).
Chemical synthesis for cajanin and its derivative has a series of relevant reports, but reaction route compares
It is long, it is unfavorable for largely preparing.The method of building talan parent nucleus is reacted with Horner-Wadsworth-Emmons to synthesize wood
Legumin needs to react (Acta Pharmaceutica Sinica B 2011 by 10 steps；1(2):93–99)；Pass through Julia alkene
The method for changing reaction building talan parent nucleus synthesizes cajanin and needs to react by 11 steps from commercially viable raw material
(Organic Letters,17(2),194-197；2015).Although the synthetic method of cajanin has certain research, however,
In all these synthetic methods, there is not yet with bromo- 4, the 6- dimethoxy benzaldehyde of 2- as starting material, it is then anti-by Heck
Substituted phenylethylene base should be connected and obtain talan structure.Also have no that aoxidizing aldehyde by Pinnick prepares Alpha-hydroxy benzene first to acid
Acid.
Summary of the invention
In order to overcome the shortcomings and deficiencies of the prior art described above, the primary purpose of the present invention is that provide a kind of raw material easy
, react that the reagent used is cheap, and step is brief, gross production rate it is high prepare cajanin and its analogue method.
The purpose of the present invention is realized by following proposal:
A kind of preparation method of cajanin and its analogue, include the following steps in (1)~(4), (1)~(5),
(1)~(6) or (1)~(7):
(1) made with the bromo- 3,5- dimethoxy benzene of 1- (compound 1 in the synthetic route chart of Fig. 1) in DMF and phosphorus oxychloride
The bromo- 4,6- dimethoxy benzaldehyde of 2- (compound 2 in the synthetic route of Fig. 1) is obtained with lower formylation；
(2) under catalyst and alkali existence condition, by bromo- 4, the 6- dimethoxy benzaldehyde of obtained 2- and R1Replace
Styrene carries out Heck coupling reaction in a solvent and obtains 2,4- dimethoxy -6-R1(the conjunction of Fig. 1 of substituted phenylethylene benzaldehyde
At the compound 3 in route map)；
(3) under reaction dissolvent existence condition, using demethylation reagent to 2,4- dimethoxy -6-R1Substituted phenylethylene base
Benzaldehyde carries out selective demethylation and obtains 2- hydroxyl -4- methoxyl group -6-R1Substituted phenylethylene benzaldehyde (the synthesis road of Fig. 1
Compound 4 in line chart)；
(4) 2- hydroxyl -4- methoxyl group -6-R1Substituted phenylethylene benzaldehyde obtains (E) -2- hydroxyl by C- isopentene group
Base -4- methoxyl group -3- (isopentene group) -6-R1Substituted phenylethylene benzaldehyde (compound 5 in the synthetic route chart of Fig. 1)；
(5) (E) -2- hydroxyl -4- methoxyl group -3- (isopentene group) -6-R1Substituted phenylethylene benzaldehyde is protected through acetyl group
Shield obtains (E) -3- (R1Substituted phenylethylene base) -2- formoxyl -5- methoxyl group -6- (isopentene group) phenylacetic acid ester (conjunction of Fig. 1
At the compound 6 in route map)；
(6)(E)-3-(R1Substituted phenylethylene base) -2- formoxyl -5- methoxyl group -6- (isopentene group) phenylacetic acid ester
Aldehyde radical aoxidizes to obtain carboxyl compound (E) -2- acetoxyl group -6- (R through Pinnick1Substituted phenylethylene base) -4- methoxyl group -3-
(isopentene group) benzoic acid (compound 7 in the synthetic route chart of Fig. 1)；
(7) by (E) -2- acetoxyl group -6- (R1Substituted phenylethylene base) -4- methoxyl group -3- (isopentene group) benzoic acid is de-
Acetyl group protection, obtains (E) -6- (R1Substituted phenylethylene base) -2- hydroxyl -4- methoxyl group -3- (isopentene group) benzoic acid (Fig. 1
Synthetic route chart in compound I).
Representation shown in the available following formula I of the structure for the product that above-mentioned step (4)~(7) obtain:
Wherein, R1=H, 2-F, 3-F, 4-F, 4-Cl, 4-CF3,4-OMe；R2=H, OH；R3=H, CH3CO；Work as R1=H, R2
=OH, R3When=H, which is the structure of cajanin；
Step (4) products therefrom is R2=H, R3Intermediate shown in Formulas I structure when=H；Step (5) products therefrom is
For R2=H, R3=CH3Intermediate shown in Formulas I structure when CO；Step (6) products therefrom is R2=OH, R3=CH3Formulas I when CO
Intermediate shown in structure；Step (7) products therefrom is R2=OH, R3Cajanin structure shown in Formulas I structure is similar when=H
Object.
The reaction temperature of formylation described in step (1) is 25~100 DEG C, and the reaction time is 4~12h；Used
The dosage of the bromo- 3,5- dimethoxy benzene of 1-, DMF and phosphorus oxychloride meets the bromo- 3,5- dimethoxy benzene of 1-, DMF and phosphorus oxychloride
Molar ratio be 1:6:3.
Reaction process in step (1) is as shown in Equation 1:
Catalyst described in step (2) can be but not limited to Pd (OAc)2,PdCl2,Pd(PPh3)4Etc. divalent or zero
Valence palladium catalyst, the amount of catalyst are catalytic amount；The alkali is potassium phosphate, and the dosage of potassium phosphate is bromo- 4, the 6- dimethoxy of 2-
1~3 times of benzaldehyde mole；The solvent is polar aprotic solvent, can be, but not limited to DMA, DMF etc. is molten
Agent；
The temperature of Heck coupling reaction described in step (2) be 100~160 DEG C, preferably 120 DEG C, the reaction time 3
~for 24 hours；2,4- dimethoxy -6- the bromobenzaldehyde and R1The dosage of substituted styrene meets 2,4- dimethoxy -6-
Bromobenzaldehyde and R1The molar ratio of substituted styrene is 1:1~5.
Reaction process in step (2) is as shown in Equation 2:
Reaction dissolvent described in step (3) can be but be not limited to hydrocarbon solvent, preferably methylene chloride；Described
Demethylation reagent is lewis acid reagent, preferably boron trihalides (such as boron chloride or Boron tribromide)；The selectivity is de-
Methyl refers to carry out at -80 DEG C~25 DEG C, and preferably 0~25 DEG C, the progress time is 1~12h；Demethylation reagent used,
2,4- dimethoxy -6-R1The dosage of substituted phenylethylene benzaldehyde meets demethylation reagent and 2,4- dimethoxy -6-R1Replace
The molar ratio of styryl benzaldehyde is 1~2:1；
Reaction process in step (3) is as shown in Equation 3:
There are two alkyl in compound 3, and using method of the present invention, that preferentially take off is C-2 alkyl, C-4
The alkyl of position does not influence, and principle is BCl3(BBr3) boron atom and the oxygen atoms of C-1 aldehyde carbonyl groups form chelating object, make
It obtains C-2 alkyl preferentially to slough, with R1For=H, principle is as shown in Equation 4:
C- isopentene group described in step (4) refers to 2- hydroxyl -4- methoxyl group -6-R1Substituted phenylethylene benzaldehyde
The iso-amylene glycosylation reaction of aryl occurs under solvent and alkaline condition with isopentene group reagent for (compound 4)；
Preferably, solvent described in step (4) is aromatic hydrocarbons (such as benzene, toluene)；The alkaline condition refers to addition
Alkali (organic bases such as such as sodium hydride, metallic sodium, potassium hydroxide inorganic base or sodium alkoxide, potassium tert-butoxide) creates alkaline condition, wherein
The dosage of alkali is 2- hydroxyl -4- methoxyl group -6-R11~1.5 times of substituted phenylethylene benzaldehyde (compound 4) mole；Institute
The isopentene group reagent stated is the sulphonic acid ester of halogenated iso-amylene or isopentene group, preferably isoprenyl bromide or isoamyl
Alkenyl p-methyl benzenesulfonic acid ester；2- hydroxyl -4- methoxyl group-the 6-R1Substituted phenylethylene benzaldehyde and isopentene group reagent
Molar ratio be 1:1~1.5；The iso-amylene glycosylation reaction of the aryl refers in 50~110 DEG C of 2~5h of reaction.
Reaction process in step (4) is as shown in Equation 5:
Y is halogen or sulfonate group, preferably bromine or p-methyl benzenesulfonic acid ester group in formula 4.
It is (different that the protection of acetyl group described in step (5) refers specifically to (E) -2- hydroxyl -4- methoxyl group -3- under alkaline condition
Pentenyl) -6-R1Substituted phenylethylene benzaldehyde and acylating reagent are in non-protonic solvent (methylene chloride, chloroform, 1,2- dichloro
Ethane, tetrahydrofuran, ether) aldehyde radical vicinal hydroxyl groups acetylization reaction occurs under existence condition, wherein alkaline condition refers to addition
Alkali (such as triethylamine, diisopropylethylamine, pyridine, N, the organic amines such as N- dimethylamino naphthyridine or inorganic base) creates alkaline condition,
Wherein the dosage of alkali is (E) -2- hydroxyl -4- methoxyl group -3- (isopentene group) -6-R1Substituted phenylethylene benzaldehyde mole
1~5 times；The acylating reagent is acyl chlorides, acylbromide or acid anhydrides；Preferably chloroacetic chloride, acetyl bromide or acetic anhydride；Aprotic
Solvent is preferably methylene chloride or chloroform；The aldehyde radical vicinal hydroxyl groups acetylization reaction refer to -10~25 DEG C react 0.5~
For 24 hours, it is preferably reacted at 0 DEG C；(E) -2- hydroxyl -4- methoxyl group -3- (isopentene group) -6-R used1Substituted phenylethylene Ji Benjia
The dosage of aldehyde and acylating reagent meets (E) -2- hydroxyl -4- methoxyl group -3- (isopentene group) -6-R1Substituted phenylethylene benzaldehyde
Molar ratio with acylating reagent is 1:1~1:5；
Reaction process in step (5) is as shown in Equation 6:
The oxidation of Pinnick described in step (6) refers to (E) -3- (R1Substituted phenylethylene base) -2- formoxyl -5- methoxy
The aldehyde radical of base -6- (isopentene group) phenylacetic acid ester is under sodium dihydrogen phosphate and solvent existence condition, with and without 2- first
Under the protection of base -2- butylene, acid is oxidized under conditions of sodium chlorite makees oxidant；Wherein solvent refers to the mixing of alcohol, ether and water
Solution, the volume of alcohol, ether and water are 1~10:1~10:1~10；The alcohol is preferably the tert-butyl alcohol；(E) -3- (R1
Substituted phenylethylene base) -2- formoxyl -5- methoxyl group -6- (isopentene group) phenylacetic acid ester, sodium dihydrogen phosphate, 2- methyl -2- fourth
The molar ratio of alkene and sodium chlorite is 1:2~10:2~100:2~10.
Reaction process in step (6) is as shown in Equation 7:
The protection of deacetylation described in step (7) refers to (E) -2- acetoxyl group -6- (R1Substituted phenylethylene base) -4- first
Oxygroup -3- (isopentene group) benzoic acid hydrolyzes under acid, base catalysis, or transesterification or alcoholysis obtain (E)-under acid, base catalysis
6-(R1Substituted phenylethylene base) -2- hydroxyl -4- methoxyl group -3- (isopentene group) benzoic acid (compound I), used in alkali can
To be but not limited to inorganic base (such as potassium carbonate, sodium hydroxide, potassium hydroxide) or organic base (such as amine, sodium alkoxide, potassium alcoholate
Deng)；Acid used can be but be not limited to the inorganic acid of such as hydrochloric acid, sulfuric acid, or the organic acid of such as acetic acid；Solvent is first
Alcohol, ethyl alcohol or tetrahydrofuran/water etc..
Preferably, the protection of deacetylation described in step (7) refers to (E) -2- acetoxyl group -6- (R1Substituted phenylethylene
Base) -4- methoxyl group -3- (isopentene group) benzoic acid in a solvent, hydrolyzed under basic conditions deacetylation protection；Wherein solvent is
Methanol, ethyl alcohol or tetrahydrofuran；Alkaline condition refers to that sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate, which is added, creates alkalinity
Condition is preferably added to sodium carbonate or potassium carbonate.
Reaction process in step (7) is as shown in Equation 8:
In above-mentioned preparation method, also step of hydrogenation can increased between step (3) and step (4), to compound 4 into
Row hydrogenation obtains double bond hydrogenated products, wherein used hydrogenation etc. is method well known to those skilled in the art, preferably
For using ethyl alcohol, methanol or ethyl acetate as solvent, hydrogen is hydrogenated as reducing agent, palladium carbon as catalyst, catalyst
Dosage is the 1%~20% of the quality of double bond containing raw material.
Cajanin analog can be further prepared in the synthetic method provided according to the present invention, such as replace step (4)
For " 2- hydroxyl -4- methoxyl group -6-R1Substituted phenylethylene benzaldehyde obtains (E) -2- hydroxyl -4- methoxyl group-by geranylgeranylation
3- (geranyl) -6-R1Substituted phenylethylene benzaldehyde ", wherein the geranylgeranylation refers to 2- hydroxyl -4- methoxyl group -6-R1
The geranylgeranylation that with geranylgeranylation reagent aryl occurs for substituted phenylethylene benzaldehyde under solvent and alkaline condition reacts；It is described
Solvent be aromatic hydrocarbons；The alkaline condition refers to that alkali, which is added, creates alkaline condition, and wherein the dosage of alkali is 2- hydroxyl -4- first
Oxygroup -6-R11~1.5 times of substituted phenylethylene benzaldehyde mole；2- hydroxyl -4- methoxyl group-the 6-R1Substituted benzene second
The molar ratio of alkenyl benzaldehyde and geranylgeranylation reagent is 1:1~1.5；The geranylgeranylation reagent is halogenated geranyl；Institute
The geranylgeranylation reaction for the aryl stated refers in 50~110 DEG C of 2~5h of reaction.
The present invention compared with the existing technology, have the following advantages and the utility model has the advantages that
Synthetic route provided by the invention: with bromo- 4, the 6- dimethoxy benzaldehyde of 2- and substituted phenylethylene for starting material,
It is chemically synthetically prepared cajanin and its analogue by 6 steps, and simple by carrying out to the synthetic method
Transformation alkylating reagent or increase step of hydrogenation can also prepare the analogue of cajanin, and the inventive method is to cajanin
The synthesis of analog has universal applicability.This lays the foundation for the further investigation of cajanin with development and application.Meanwhile also for
The synthesis of cajanin analogue and structure activity study and the more preferable toxicity of searching activity are lower similar with cajanin
The novel drug candidate of skeleton structure lays the foundation.
Detailed description of the invention
Fig. 1 is the synthetic route chart of cajanin and its analogue.
Specific embodiment
Below with reference to embodiment and attached drawing, the present invention is described in further detail, but embodiments of the present invention are unlimited
In this.
Agents useful for same can routinely be bought unless otherwise specified from market in embodiment.
DMA used represents n,N-dimethylacetamide in embodiment, and DCM represents methylene chloride, and DMAP represents 4- diformazan ammonia
Yl pyridines, TEA represent triethylamine, and THF represents tetrahydrofuran.
Required reaction raw materials in embodiment, i.e. bromo- 4, the 6- dimethoxy benzaldehyde of 2-, bibliography preparation
(Quach,R.；Daniel P.F.；Margaret A.B.J.Org.Chem.2016,81,8343-8350.)
The preparation of embodiment 1:2,4- dimethoxy-6-styryl benzaldehyde
The bromo- 4,6- dimethoxy benzaldehyde (5.0g, 20.4mmol) of 2- and styrene (3.5mL, 30.6mmol) are dissolved in
25mL DMAC N,N' dimethyl acetamide, then sequentially adds K3PO4(6.5g, 30.6mmol), palladium acetate (0.46g, 2.05mmol).
120 DEG C of 3~4h of reaction are warming up to, reaction becomes black at this time.Reaction is cooled to room temperature and 100mL water, ethyl acetate is then added
It extracts (3 × 50mL), merges organic phase, successively use water (1 × 100mL), saturated salt solution (1 × 100mL) washing, anhydrous slufuric acid
Sodium dries, filters and solvent is evaporated off under decompression, and silica gel column purification (petroleum ether: ethyl acetate=5:1) obtains yellow solid 5.2g, receives
Rate 95%, following characterize data explanation successfully synthesize target product.
1H NMR(300MHz,CDCl3): δ 10.53 (d, J=0.6Hz, 1H), 8.17 (d, J=16.2Hz, 1H), 7.62-
7.53 (m, 2H), 7.42-7.32 (m, 2H), 7.31-7.23 (m, 1H), 7.00 (d, J=16.2Hz, 1H), 6.75 (d, J=
2.2Hz, 1H), 6.40 (d, J=2.2Hz, 1H), 3.91 (s, 3H), 3.88 (s, 3H)
13C NMR(75MHz,CDCl3): δ 190.6,165.1,164.7,142.9,137.3,132.5,128.7,128.1,
127.9,127.1,116.3,103.8,97.3,56.0,55.7
HRMS (ESI): Found (M+H)+,269.1184.C17H17O3Calc.(M+H)+,269.1172.
The preparation of embodiment 2:2- hydroxyl -4- methoxyl group -6- styryl benzaldehyde
Compound 3 (5.2g, 19.4mmol) is dissolved in 100mL dry methylene chloride, and BCl is added dropwise at 0 DEG C3Dichloromethane
Alkane solution (29mL, 1M), drips off, and reacts at room temperature 1h, stops reaction.Reaction solution washing, anhydrous sodium sulfate are dry.Filtering, decompression
Solvent is evaporated off, residue obtains white solid 4.9g, yield 98% with (petroleum ether: ethyl acetate=5:1) silica gel column purification.Below
Data explanation successfully synthesizes target product.
1H NMR:(300MHz,CDCl3)δ12.49(s,1H),10.20(s,1H),7.56–7.45(m,3H),7.45–
7.28 (m, 3H), 6.98 (d, J=15.9Hz, 1H), 6.61 (d, J=2.3Hz, 1H), 6.37 (d, J=2.3Hz, 1H), 3.87
(s,3H)
13C NMR:(75MHz,CDCl3)δ193.0,166.7,166.3,144.4,136.4,135.7,129.0,128.8,
127.0,122.9,112.5,107.1,100.0,55.8
HRMS(ESI):Found(M+H)+,255.1019.C16H15O3Calc.(M+H)+,255.1016.
Embodiment 3:(E) -2- hydroxyl -4- methoxyl group -3- (isopentene group) -6- styryl benzaldehyde preparation
Compound 4 (4.9g, 19.3mmol) is dissolved in 50mL toluene, and sodium hydride (1.0g, 25.0mmol) is added at 0 DEG C,
0.5h is stirred at room temperature, is added isoprenyl bromide (4.3g, 28.9mmol), is warming up to 65 DEG C of reaction 4h, stops reaction, is cooled to room
Water is added in temperature, separates organic layer, then extracted with ethyl acetate (2 × 50mL), merges organic layer, wash (1 × 100mL), saturation
Salt washes (1 × 100mL).Anhydrous sodium sulfate dries, filters, and evaporating solvent under reduced pressure obtains yellow oil, silica gel column purification, stone
Oily ether: ethyl acetate=100:1 elution obtains yellow oily liquid 2.8g (yield 45%).Following data explanation successfully synthesizes
Target product.
1H NMR(300MHz,CDCl3):δ12.41(s,1H),10.23(s,1H),7.60-7.48(m,3H),7.45-
7.29 (m, 3H), 6.95 (d, J=15.9Hz, 1H), 6.61 (s, 1H), 5.21 (tdt, J=5.7,2.8,1.4Hz, 1H), 3.96
(s, 3H), 3.36 (d, J=7.2Hz, 2H), 1.80 (d, J=1.4Hz, 3H), 1.69 (d, J=1.4Hz, 3H)
13C NMR(75MHz,CDCl3):δ193.3,163.8,162.4,142.5,136.5,135.2,132.3,129.0,
128.7,126.9,123.6,121.8,116.9,112.9,102.0,56.0,26.0,21.6,17.9.
HRMS(ESI):Found(M+H)+,323.1650.C21H23O3Calc.(M+H)+,323.1642.
Embodiment 4:(E) -3- styryl -2- formoxyl -5- methoxyl group -6- (isopentene group) phenylacetic acid ester preparation
Compound 5 (2.8g, 8.7mmol) is dissolved in 40mL methylene chloride, successively triethylamine (1.2g, 11.3mmol) at 0 DEG C
With acetic anhydride (1.1g, 10.4mmol), it is kept at this temperature 1h.It quenches when saturated aqueous ammonium chloride after the reaction was completed, is added
It goes out, separates organic layer, then extracted with methylene chloride (2 × 50mL), merge dichloromethane layer, anhydrous sodium sulfate dries, filters, subtracts
It is product 3.2g (yield 100%) that pressure, which is evaporated off solvent to obtain yellow solid,.Following characterize data explanation successfully synthesizes target production
Object.
1H NMR:(300MHz,CDCl3) δ 10.23 (s, 1H), 7.83 (d, J=16.1Hz, 1H), 7.59-7.50 (m,
2H), 7.43-7.34 (m, 2H), 7.34-7.27 (m, 1H), 6.93 (s, 1H), 6.95 (d, J=16.1,2H), 5.10 (tt, J=
7.1,1.4Hz, 1H), 3.97 (s, 3H), 3.28 (d, J=7.0Hz, 2H), 2.40 (s, 3H), 1.77 (d, J=1.4Hz, 3H),
1.69 (d, J=1.4Hz, 3H)
13C NMR:(75MHz,CDCl3)δ188.6,169.5,162.2,151.2,142.0,136.7,134.6,132.5,
128.9,128.5,127.1,125.5,123.4,121.0,119.2,107.0,56.1,25.8,23.0,20.9,17.9.
HRMS(ESI):Found(M+H)+,365.1759.C23H25O4Calc.(M+H)+,365.1747.
Embodiment 5:(E) -2- acetoxyl group -6- styryl -4- methoxyl group -3- (isopentene group) benzoic acid preparation
Compound 6 (3.2g, 8.7mmol) is dissolved in the 20mL tert-butyl alcohol, the mixed solvent of 10mL tetrahydrofuran and water 5mL,
Then sequentially add sodium dihydrogen phosphate dihydrate (2.7g, 17.4mmol), 2- methyl-2-butene (4.1g, 52.2mmol) and
Sodium chlorite (6.8g, 34.8mmol), is stirred at room temperature 1h, after reaction addition 20mL water, ethyl acetate extraction (3 ×
50mL), merge organic layer, saturated common salt water washing, anhydrous sodium sulfate dries, filters, evaporating solvent under reduced pressure, petroleum ether: acetic acid
Ethyl ester silica gel column purification obtains white solid 2.65g (yield 80%).Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 10.76 (s, 1H), 7.62 (d, J=16.1Hz, 1H), 7.53 (d, J=
7.5Hz, 2H), 7.36 (t, J=7.4Hz, 2H), 7.29 (d, J=7.2Hz, 1H), 7.07 (s, 1H), 7.01 (d, J=
16.1Hz, 1H), 5.13 (t, J=7.0Hz, 1H), 3.97 (s, 3H), 3.28 (d, J=7.0Hz, 2H), 2.31 (s, 3H), 1.77
(s,3H),1.70(s,3H).
13C NMR(75MHz,CDCl3):δ172.0,169.5,160.4,149.1,138.6,137.0,132.3,131.8,
128.8,128.2,127.0,126.9,123.5,121.2,116.1,106.2,56.0,25.8,23.5,20.9,17.9.
HRMS(ESI):Found(M-H)-,379.1549.C23H23O5Calc.(M-H)-,379.1551.
Embodiment 6: the preparation of cajanin
Compound 7 (1g, 2.6mmol) is dissolved in 15mL methanol, is added potassium carbonate (0.43g, 3.1mmol), stirs at room temperature
1h is mixed, end of reaction is added water (20mL), and ethyl acetate extracts (3 × 30mL), merges organic layer, washes, then saturated common salt
Washing, anhydrous sodium sulfate dry, filter, and evaporating solvent under reduced pressure, petroleum ether: ethyl acetate silica gel column purification obtains white solid
0.82g (yield 93%).Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,Acetone-d6): δ 12.27 (s, 1H), 8.08-7.91 (m, 1H), 7.69-7.51 (m,
2H), 7.38 (ddd, J=7.9,6.5,1.6Hz, 2H), 7.28 (td, J=7.1,1.5Hz, 1H), 7.01 (dd, J=16.1,
1.6Hz, 1H), 6.87 (d, J=1.5Hz, 1H), 5.22 (tt, J=5.8,2.9Hz, 1H), 3.98 (d, J=1.6Hz, 3H),
3.36 (d, J=7.3Hz, 2H), 1.77 (s, 3H), 1.64 (s, 3H)
13C NMR(75MHz,Acetone-d6): δ 174.2,163.0,162.4,141.8,138.7,131.5,131.2,
131.2,129.5,128.5,127.5,123.2,116.9,104.8,103.4,56.2,25.9,22.7,17.9.
HRMS (ESI): Found (M-H)-,337.1441.C21H21O4Calc.(M-H)-,337.1445.
Embodiment 7:(E) -2- (2- fluorostyryl) -4,6- dimethoxy benzaldehyde preparation
Compound, white solid (82%) are obtained using 2- fluorobenzene ethene as starting material in the similar method of embodiment 1.With
Lower characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 10.52 (s, 1H), 8.18 (d, J=16.4Hz, 1H), 7.73 (td, J=7.7,
1.8Hz, 1H), 7.28-7.10 (m, 3H), 7.05 (ddd, J=10.7,8.1,1.3Hz, 1H), 6.76 (d, J=2.2Hz, 1H),
6.41 (d, J=2.2Hz, 1H), 3.91 (s, 3H), 3.89 (s, 3H)
13C NMR(75MHz,CDCl3): δ 190.6,165.1,164.8,162.2,158.9,142.7,130.0,129.9,
129.4,129.3,127.4,127.4,125.2,125.1,124.4,124.4,124.2,124.1,116.4,115.8,
115.6,104.0,97.5,56.0,55.7
HRMS (ESI): Found (M+H)+,287.1078.C17H14FO3Calc.(M+H)+,287.1065.
Embodiment 8:(E) preparation of -2- (2- fluorostyryl) -6- hydroxyl -4-methoxybenzaldehyde
Using 7 product of embodiment as raw material, compound, white solid (95%) are obtained in the similar method of embodiment 2.Below
Characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 12.47 (s, 1H), 10.19 (s, 1H), 7.60 (d, J=16.2Hz, 1H), 7.54
(dd, J=7.6,1.8Hz, 1H), 7.34-7.26 (m, 1H), 7.21-7.11 (m, 2H), 7.11-7.05 (m, 1H), 6.63 (d, J
=2.4Hz, 1H), 6.38 (d, J=2.4Hz, 1H), 3.88 (s, 3H)
13C NMR(75MHz,CDCl3)δ192.9,166.7,166.3,144.2,130.1,128.2,128.2,127.9,
127.9,125.6,124.5,124.5,116.3,116.0,112.4,107.2,100.2,55.8
HRMS(ESI)Found(M+H)+,273.0924.C16H13FO3Calc.(M+H)+,273.0921.
Embodiment 9:(E) -6- (2- fluorostyryl) -2- hydroxyl -4- methoxyl group -3- (isopentene group) benzaldehyde preparation
Using 8 product of embodiment as raw material, compound, white solid (43%) are obtained in the similar method of embodiment 3.Below
Characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 12.41 (s, 1H), 10.22 (s, 1H), 7.65 (d, J=16.1Hz, 1H), 7.57
(td, J=7.7,1.8Hz, 1H), 7.34-7.26 (m, 1H), 7.22-7.14 (m, 1H), 7.14-7.04 (m, 2H), 6.62 (s,
1H), 5.21 (dddd, J=7.1,5.7,2.8,1.4Hz, 1H), 3.97 (s, 3H), 3.36 (d, J=7.1Hz, 2H), 1.80 (s,
3H), 1.69 (d, J=1.4Hz, 3H)
13C NMR(75MHz,CDCl3)δ193.2,163.8,162.4,142.3,132.3,130.0,129.9,127.8,
127.7,127.6,126.2,126.1,124.5,121.7,117.1,116.3,116.0,112.8,102.0,56.0,26.0,
21.6,17.9.
HRMS(ESI)Found(M+H)+,341.1552.C21H20FO3Calc.(M+H)+,341.1547。
Embodiment 10:(E) -3- (2- fluorostyryl) -2- formoxyl -5- methoxyl group -6- (isopentene group) phenylacetic acid
The preparation of ester
Using 9 product product of embodiment as raw material, compound, white solid (98%) are obtained in the similar method of embodiment 4.
Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 10.25 (s, 1H), 7.95 (d, J=16.2Hz, 1H), 7.67 (td, J=7.7,
1.8Hz, 1H), 7.30 (tdd, J=7.3,5.2,1.8Hz, 1H), 7.22-7.06 (m, 3H), 7.00 (s, 1H), 5.11 (tdd, J
=7.0,2.9,1.4Hz, 1H), 4.00 (s, 3H), 3.29 (d, J=7.0Hz, 2H), 2.42 (s, 3H), 1.81-1.74 (m,
3H), 1.71 (d, J=1.4Hz, 3H)
13C NMR(75MHz,CDCl3)δ188.6,169.5,162.3,151.5,141.7,132.6,129.8,129.7,
128.0,127.6,127.6,126.4,124.5,124.5,123.7,120.9,119.2,116.1,115.8,107.1,56.2,
25.8,23.1,20.9,17.9
HRMS(ESI)Found(M+H)+,405.1478.C23H22FO4Calc.(M+H)+,405.1473。
Embodiment 11:(E) -2- acetoxyl group -6- (2- fluorostyryl) -4- methoxyl group -3- (isopentene group) benzoic acid
Preparation
Using 10 product of embodiment as raw material, compound is obtained in the similar method of embodiment 5, white solid (90%), with
Lower characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,Acetone-d6) δ 7.70-7.55 (m, 2H), 7.30 (d, J=7.1Hz, 3H), 7.23-
7.08 (m, 2H), 5.08 (tt, J=7.1,1.5Hz, 1H), 3.98 (s, 3H), 3.22 (d, J=7.1Hz, 2H), 2.23 (s,
3H), 1.71 (d, J=1.4Hz, 3H), 1.62 (d, J=1.4Hz, 3H)
13C NMR(75MHz,Acetone-d6)δ169.1,167.4,160.2,149.1,137.0,132.3,130.4,
130.3,129.9,129.9,128.6,128.6,125.9,125.8,125.5,125.4,124.2,124.0,124.0,
122.3,120.1,116.7,116.4,106.2,56.5,25.8,24.0,20.8,17.9
HRMS(ESI)Found(M-H)-,397.1457.C23H23FO5Calc.(M-H)-,397.1457。
Embodiment 12:(E) -6- (2- fluorostyryl) -2- hydroxyl -4- methoxyl group -3- (isopentene group) benzoic acid system
It is standby
Using 11 product of embodiment as raw material, compound is obtained in the similar method of embodiment 6, white solid (97%), with
Lower characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,Acetone-d6) δ 8.09 (dd, J=16.1,2.8Hz, 1H), 7.71 (tq, J=7.8,
1.8Hz, 1H), 7.33 (dddq, J=8.6,5.2,3.3,1.7Hz, 1H), 7.26-7.11 (m, 2H), 7.07 (dd, J=16.2,
2.8Hz, 1H), 6.85 (d, J=2.8Hz, 1H), 5.22 (tq, J=5.7,1.8Hz, 1H), 4.00 (d, J=2.9Hz, 3H),
3.44-3.31 (m, 2H), 1.77 (d, J=2.5Hz, 3H), 1.64 (q, J=1.5Hz, 3H)
13C NMR(75MHz,Acetone-d6)δ174.0,162.9,162.4,141.6,134.0,133.9,131.6,
130.1,130.0,128.5,128.5,125.4,125.4,123.1,123.1,123.0,117.2,116.6,116.4,
104.9,103.6,56.2,25.9,22.7,17.9.
HRMS(ESI)Found(M-H)-,355.1353.C21H22FO4Calc.(M-H)-,355.1351。
Embodiment 13:(E) -2- (3- fluorostyryl) -4,6- dimethoxy benzaldehyde preparation
Compound is obtained using 3- fluorobenzene ethene as starting material in the similar method of embodiment 1, white solid (85%), with
Lower characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 10.53 (d, J=0.6Hz, 1H), 8.14 (d, J=16.1Hz, 1H), 7.35-
7.29 (m, 2H), 7.29-7.23 (m, 1H), 7.02-6.88 (m, 2H), 6.73 (d, J=2.2Hz, 1H), 6.42 (d, J=
2.2Hz,1H),3.92(s,3H),3.90(s,3H)
13C NMR(75MHz,CDCl3): δ 190.6,165.1,164.8,142.3,139.7,131.1,130.2,130.1,
129.4,123.0,122.9,116.3,114.9,114.6,113.6,113.3,104.1,97.5,56.0,55.7.
HRMS(ESI)Found(M+H)+,287.1078.C17H15FO3Calc.(M+H)+,287.1078.
Embodiment 14:(E) preparation of -2- (3- fluorostyryl) -6- hydroxyl -4-methoxybenzaldehyde
Using the product of embodiment 13 as raw material, compound, white solid are obtained in the similar method of embodiment 2
(96%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 12.48 (s, 1H), 10.18 (s, 1H), 7.49 (d, J=15.9Hz, 1H), 7.36
(td, J=7.9,5.8Hz, 1H), 7.29-7.17 (m, 2H), 7.03 (tdd, J=8.2,2.6,1.1Hz, 1H), 6.93 (d, J=
15.9Hz, 1H), 6.61 (dd, J=2.4,0.7Hz, 1H), 6.39 (d, J=2.4Hz, 1H), 3.88 (s, 3H)
13C NMR(75MHz,CDCl3)δ192.7,166.6,166.3,164.8,161.6,143.7,138.7,138.6,
134.3,134.3,130.5,130.4,124.3,122.9,122.9,115.7,115.4,113.5,113.2,112.4,
107.2,100.2,55.8.
HRMS(ESI)Found(M+H)+,273.0920.C16H13FO3Calc.(M+H)+,273.0921.
Embodiment 15:(E) -6- (3- fluorostyryl) -2- hydroxyl -4- methoxyl group -3- (isopentene group) benzaldehyde system
It is standby
Using the product of embodiment 14 as raw material, compound, yellow solid are obtained in the similar method of embodiment 3
(46%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 12.42 (s, 1H), 10.22 (s, 1H), 7.56 (d, J=15.9Hz, 1H), 7.37
(td, J=7.9,5.8Hz, 1H), 7.33-7.27 (m, 1H), 7.23 (dt, J=10.0,2.1Hz, 1H), 7.04 (tdd, J=
8.2,2.6,1.1Hz, 1H), 6.92 (d, J=15.9Hz, 1H), 6.61 (s, 1H), 5.23 (tdd, J=5.7,2.9,1.4Hz,
1H), 3.98 (s, 3H), 3.38 (d, J=7.2Hz, 2H), 1.86-1.78 (m, 3H), 1.71 (d, J=1.4Hz, 3H)
13C NMR(75MHz,CDCl3)δ193.1,164.9,163.8,162.4,161.6,141.9,138.9,138.8,
133.9,133.9,132.3,130.5,130.4,125.0,122.9,122.8,121.7,117.2,115.6,115.3,
113.4,113.2,112.9,102.0,56.0,25.9,21.6,17.9.
HRMS(ESI)Found(M+H)+,341.1540.C21H23FO3Calc.(M+H)+,341.1547.
Embodiment 16:(E) -3- (3- fluorostyryl) -2- formoxyl -5- methoxyl group -6- (isopentene group) phenylacetic acid
The preparation of ester
Using the product of embodiment 15 as raw material, compound, yellow solid are obtained in the similar method of embodiment 4
(96%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 10.22 (s, 1H), 7.86 (d, J=16.1Hz, 1H), 7.40-7.21 (m, 3H),
7.05-6.95 (m, 2H), 6.91 (d, J=16.1Hz, 1H), 5.11 (ddt, J=7.0,5.6,1.4Hz, 1H), 3.98 (s,
3H), 3.29 (d, J=7.0Hz, 2H), 2.41 (s, 3H), 1.81-1.75 (m, 3H), 1.71 (d, J=1.4Hz, 3H)
13C NMR(75MHz,CDCl3)δ188.5,169.5,164.8,162.1,161.5,151.6,141.2,139.1,
139.0,133.0,132.9,132.6,130.3,130.2,127.1,123.6,122.9,122.9,120.9,119.2,
115.3,115.0,113.5,113.2,107.0,56.1,25.8,23.0,20.8,17.9.
HRMS(ESI)Found(M+H)+,383.1654.C23H23FO4Calc.(M+H)+,383.1653.
Embodiment 17:(E) -2- acetoxyl group -6- (3- fluorostyryl) -4- methoxyl group -3- (isopentene group) benzoic acid
Preparation
Using the product of embodiment 16 as raw material, compound, white solid are obtained in the similar method of embodiment 5
(90%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 7.61 (d, J=16.0Hz, 1H), 7.30 (td, J=4.1,2.7Hz, 2H),
7.26-7.15 (m, 1H), 7.10-6.88 (m, 4H), 5.12 (t, J=7.0Hz, 1H), 3.98 (s, 3H), 3.29 (d, J=
7.1Hz,2H),2.32(s,3H),1.77(s,3H),1.70(s,3H).
13C NMR(75MHz,CDCl3)δ171.4,169.5,164.9,160.5,149.2,139.5,138.2,132.5,
130.6,130.3,130.2,128.4,124.0,122.8,121.1,116.2,115.1,114.8,113.6,113.3,
106.3,56.1,25.9,23.6,20.9,17.9.
HRMS(ESI)Found(M-H)-,397.1450.C23H23FO5Calc.(M-H)-,397.1457.
Embodiment 18:(E) -6- (3- fluorostyryl) -2- hydroxyl -4- methoxyl group -3- (isopentene group) benzoic acid system
It is standby
Using the product of embodiment 17 as raw material, compound, white solid are obtained in the similar method of embodiment 6
(96%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,Acetone-d6) δ 8.04 (d, J=16.0Hz, 1H), 7.48-7.36 (m, 2H), 7.32
(dt, J=9.8,2.1Hz, 1H), 7.10-6.95 (m, 2H), 6.85 (s, 1H), 5.21 (tdd, J=5.8,2.9,1.4Hz,
1H), 3.97 (s, 3H), 3.35 (d, J=7.3Hz, 2H), 1.77 (d, J=1.3Hz, 3H), 1.64 (d, J=1.4Hz, 3H)
13C NMR(75MHz,Acetone-d6)δ174.1,165.6,162.9,162.4,141.3,132.7,131.6,
131.4,131.2,129.8,123.7,123.6,123.1,117.1,115.1,114.8,113.7,113.4,104.9,
103.5,56.2,25.9,22.7,17.9.
HRMS(ESI)Found(M-H)-,355.1356.C21H22FO4Calc.(M-H)-,355.1351.
Embodiment 19:(E) -2,4- dimethoxy -6- (4- (trifluoromethyl) styryl) benzaldehyde preparation
Using 4- trifluoromethyl styrene as raw material, compound, yellow solid are obtained in the similar method of embodiment 1
(89%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 10.52 (s, 1H), 8.21 (d, J=16.2Hz, 1H), 7.63 (d, J=8.4Hz,
2H), 7.58 (d, J=8.5Hz, 2H), 6.97 (d, J=16.2Hz, 1H), 6.73 (d, J=2.2Hz, 1H), 6.42 (d, J=
2.3Hz,1H),3.91(s,3H),3.89(s,3H)
13C NMR(75MHz,CDCl3)δ190.7,165.2,164.9,142.1,140.8,130.8,130.7,127.2,
125.7,125.6,116.4,104.2,97.7,56.0,55.7
HRMS(ESI)Found(M+H)+,337.1049.C18H15F3O3Calc.(M+H)+,337.1046.
Embodiment 20:(E) -2- hydroxyl -4- methoxyl group -6- (4- (trifluoromethyl) styryl) benzaldehyde preparation
Using 19 product of embodiment as raw material, compound is obtained in the similar method of embodiment 2, yellow solid (96%),
Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 12.46 (s, 1H), 10.17 (s, 1H), 7.63 (d, J=8.5Hz, 2H), 7.58
(d, J=8.5Hz, 2H), 7.65 (d, J=16.0Hz, 1H), 6.98 (d, J=16.0Hz, 1H), 6.61 (d, J=2.3Hz,
1H), 6.38 (d, J=2.3Hz, 1H), 3.87 (s, 3H)
13C NMR(75MHz,CDCl3)δ192.6,166.7,166.3,143.5,139.8,134.0,127.1,125.9,
125.9,125.5,112.4,107.4,100.4,55.8
HRMS(ESI)Found(M+H)+,323.0900.C17H12F3O3Calc.(M+H)+,323.0890.
Embodiment 21:(E) -2- hydroxyl -4- methoxyl group -3- (isopentene group) -6- (4- (trifluoromethyl) styryl) benzene
The preparation of formaldehyde
Using 20 product of embodiment as raw material, compound is obtained in the similar method of embodiment 3, yellow solid (40%),
Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3)δ12.38(s,1H),10.22(s,1H),7.69–7.56(m,5H),6.96(d,J
=16.0Hz, 1H), 6.61 (s, 1H), 5.20 (tt, J=7.2,1.5Hz, 1H), 3.97 (s, 3H), 3.36 (d, J=7.2Hz,
2H), 1.79 (d, J=1.4Hz, 3H), 1.69 (d, J=1.4Hz, 3H)
13C NMR(75MHz,CDCl3)δ193.0,163.8,162.5,141.7,133.6,132.4,127.1,126.3,
126.0,125.9,121.6,117.5,112.9,102.2,56.0,26.0,21.7,17.9
HRMS(ESI)Found(M+H)+,391.1519.C22H21F3O3Calc.(M+H)+,391.1516.
Embodiment 22:(E) -2- formoxyl -5- methoxyl group -6- (isopentene group) -3- (4- (trifluoromethyl) styryl)
The preparation of phenylacetic acid ester
Using 21 product of embodiment as raw material, compound is obtained in the similar method of embodiment 4, yellow solid (98%),
Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 10.20 (s, 1H), 7.96 (d, J=16.1Hz, 1H), 7.61 (s, 4H), 7.01-
6.88 (m, 2H), 5.09 (ddt, J=7.0,5.6,1.5Hz, 1H), 3.97 (s, 3H), 3.27 (d, J=7.0Hz, 2H), 2.39
(s, 3H), 1.76 (d, J=1.4Hz, 3H), 1.69 (d, J=1.4Hz, 3H)
13C NMR(75MHz,CDCl3)δ188.6,169.5,162.2,151.9,140.8,140.3,132.7,132.4,
128.6,127.2,125.8,125.8,123.9,120.8,119.3,107.0,56.1,25.8,23.1,20.8,17.9
HRMS(ESI)Found(M+H)+,433.1632.C24H23F3O3Calc.(M+H)+,433.0621.
Embodiment 23:(E) -2- acetoxyl group -4- methoxyl group -3- (isopentene group) -6- (4- (trifluoromethyl) styrene
Base) benzoic acid preparation
Using 22 product of embodiment as raw material, compound is obtained in the similar method of embodiment 5, yellow solid (89%),
Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 7.67 (d, J=16.0Hz, 1H), 7.58 (s, 4H), 7.03 (s, 1H), 6.98
(d, J=16.0Hz, 1H), 5.10 (ddq, J=7.2,5.8,1.5Hz, 1H), 3.96 (s, 3H), 3.28 (d, J=7.2Hz,
2H), 2.30 (s, 3H), 1.75 (d, J=1.3Hz, 3H), 1.69 (d, J=1.5Hz, 3H)
13C NMR(75MHz,CDCl3)δ171.5,169.6,160.6,149.3,140.5,138.0,132.6,130.2,
129.6,127.1,125.8,125.7,124.2,121.0,116.3,106.4,56.1,25.8,23.6,20.9,17.9
HRMS(ESI)Found(M-H)-,447.1426.C22H21F3O4Calc.(M-H)-,447.1425.
Embodiment 24:(E) -2- hydroxyl -4- methoxyl group -3- (isopentene group) -6- (4- (trifluoromethyl) styryl) benzene
The preparation of formic acid
Using 23 product of embodiment as raw material, compound is obtained in the similar method of embodiment 6, white solid (96%),
Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,Acetone-d6) δ 12.29 (s, 1H), 8.14 (d, J=16.1Hz, 1H), 7.77 (d, J=
8.2Hz, 2H), 7.71 (d, J=8.2Hz, 2H), 7.08 (d, J=16.1Hz, 1H), 6.88 (s, 1H), 5.21 (tt, J=7.2,
1.6Hz, 1H), 3.98 (s, 3H), 3.36 (d, J=7.2Hz, 2H), 1.77 (s, 3H), 1.64 (s, 3H)
13C NMR(75MHz,Acetone-d6)δ174.1,163.0,162.4,141.1,134.1,131.7,129.5,
128.0,126.5,126.4,123.1,117.4,105.0,103.7,56.2,25.9,22.7,17.9.
HRMS(ESI)Found(M-H)-,405.1331.C22H21F3O4Calc.(M-H)-,405.1319.
Embodiment 25:(E) -2- (4- chlorostyrene base) -4,6- dimethoxy benzaldehyde preparation
Using 4- chlorostyrene base as raw material, compound, yellow solid are obtained in the similar method of embodiment 1
(90%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 10.47 (s, 1H), 8.09 (d, J=16.1Hz, 1H), 7.43 (d, J=8.5Hz,
2H), 7.27 (d, J=8.5Hz, 2H), 6.88 (d, J=16.1Hz, 1H), 6.67 (d, J=2.2Hz, 1H), 6.34 (d, J=
2.2Hz,1H),3.86(s,3H),3.83(s,3H)
13C NMR(75MHz,CDCl3)δ190.5,165.0,164.6,142.2,135.8,133.4,130.8,128.7,
128.5,128.2,116.1,103.8,97.2,55.8,55.5
HRMS(ESI)Found(M+H)+,303.0787.C17H15ClO3Calc.(M+H)+,303.0782.
Embodiment 26:(E) -2- (4- chlorostyrene base) -6- hydroxyl -4-methoxybenzaldehyde preparation
Using 25 product of embodiment as raw material, compound is obtained in the similar method of embodiment 2, white solid (96%),
Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 12.45 (s, 1H), 10.18 (s, 1H), 7.47 (d, J=15.9Hz, 1H), 7.43
(d, J=8.5Hz, 2H), 7.35 (d, J=8.5Hz, 2H), 6.92 (d, J=15.9Hz, 1H), 6.59 (d, J=2.4Hz, 1H),
6.37 (d, J=2.4Hz, 1H), 3.87 (s, 3H)
13C NMR(75MHz,CDCl3)δ192.8,166.7,166.3,144.0,134.9,134.5,134.4,129.2,
128.2,123.6,112.5,107.2,100.2,55.9.
HRMS(ESI)Found(M+H)+,289.0627.C16H13ClO3Calc.(M+H)+,289.0626.
Embodiment 27:(E) -6- (4- chlorostyrene base) -2- hydroxyl -4- methoxyl group -3- (isopentene group) benzaldehyde system
It is standby
Using 26 product of embodiment as raw material, compound is obtained in the similar method of embodiment 3, white solid (45%),
Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 12.40 (s, 1H), 10.18 (s, 1H), 7.49 (d, J=16.0Hz, 1H), 7.43
(d, J=8.6Hz, 2H), 7.34 (d, J=8.6Hz, 2H), 6.88 (d, J=16.0Hz, 1H), 6.58 (s, 1H), 5.21 (tt, J
=7.2,1.4Hz, 1H), 3.95 (s, 3H), 3.35 (d, J=7.2Hz, 2H), 1.80 (s, 3H), 1.69 (s, 3H)
13C NMR(75MHz,CDCl3)δ193.1,163.8,162.3,142.0,135.0,134.3,133.7,132.2,
129.1,128.1,124.2,121.6,117.0,112.8,101.9,55.9,25.9,21.6,17.9
HRMS(ESI)Found(M+H)+,357.1265.C21H21ClO3Calc.(M+H)+,357.1252.
Embodiment 28:(E) -3- (4- chlorostyrene base) -2- formoxyl -5- methoxyl group -6- (isopentene group) phenylacetic acid
The preparation of ester
Using 27 product of embodiment as raw material, compound is obtained in the similar method of embodiment 4, white solid (98%),
Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3) δ 10.20 (s, 1H), 7.83 (d, J=16.1Hz, 1H), 7.45 (d, J=8.5Hz,
2H), 7.33 (d, J=8.5Hz, 2H), 6.94 (s, 1H), 6.88 (d, J=16.1Hz, 1H), 5.09 (dddd, J=8.5,5.6,
2.7,1.3Hz, 1H), 3.96 (s, 3H), 3.26 (d, J=7.0Hz, 2H), 2.39 (s, 3H), 1.76 (s, 3H), 1.68 (s, 3H)
13C NMR(75MHz,CDCl3)δ188.6,169.5,162.2,151.6,141.4,135.3,134.1,133.0,
132.6,129.0,128.2,126.4,123.6,120.9,119.2,107.0,56.1,25.8,23.1,20.8,17.9
HRMS(ESI)Found(M+H)+,399.1368.C23H23ClO4Calc.(M+H)+,399.1358.
Embodiment 29:(E) -2- acetoxyl group -6- (4- chlorostyrene base) -4- methoxyl group -3- (isopentene group) benzoic acid
Preparation
Using 28 product of embodiment as raw material, compound is obtained in the similar method of embodiment 5, white solid (86%),
Following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,Acetone-d6) δ 7.54 (d, J=16.2Hz, 1H), 7.54 (d, J=8.6Hz, 2H),
7.38 (d, J=8.6Hz, 2H), 7.29 (s, 1H), 7.24 (d, J=16.2Hz, 1H), 5.11 (tt, J=7.1,1.5Hz, 1H),
3.97 (s, 3H), 3.24 (d, J=7.1Hz, 2H), 2.26 (s, 3H), 1.74 (s, 3H), 1.64 (s, 3H)
13C NMR(75MHz,Acetone-d6): δ 169.0,167.4,160.0,148.9,136.9,136.8,133.6,
132.1,130.4,129.5,128.9,127.7,123.9,122.2,119.8,106.0,56.3,25.7,23.9,20.7,
17.8.
HRMS (ESI): Found (M-H)-,413.1179.C23H23ClO5Calc.(M-H)-,413.1161.
Embodiment 30:(E) -6- (4- chlorostyrene base) -2- hydroxyl -4- methoxyl group -3- (isopentene group) benzoic acid system
It is standby
Using 29 product of embodiment as raw material, compound is obtained with the similar approach of embodiment 6, white solid (98%), with
Lower characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,Acetone-d6): δ 8.00 (d, J=16.0Hz, 1H), 7.57 (d, J=8.5Hz, 2H),
7.39 (d, J=8.5Hz, 2H), 6.99 (d, J=16.0Hz, 1H), 6.84 (s, 1H), 5.21 (ddt, J=7.3,5.8,
1.5Hz, 1H), 3.97 (s, 3H), 3.35 (d, J=7.3Hz, 2H), 1.76 (s, 3H), 1.63 (s, 3H)
13C NMR(75MHz,Acetone-d6): δ 174.1,162.9,162.3,141.4,137.5,133.5,132.0,
131.5,129.5,129.0,123.1,117.0,104.9,103.4,56.1,25.9,22.7,17.8
HRMS (ESI): Found (M-H)-,317.1063.C21H21ClO4Calc.(M-H)-,371.1056.
Embodiment 31:(E) -2- (4- fluorostyryl) -4,6- dimethoxy benzaldehyde preparation
Using 4- fluorobenzene ethene as raw material, compound is obtained in the similar method of embodiment 1, white solid (83%), with
Lower characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 10.52 (s, 1H), 8.07 (d, J=16.2Hz, 1H), 7.57-7.47 (m,
2H), 7.09-6.99 (m, 2H), 6.94 (d, J=16.2Hz, 1H), 6.72 (d, J=2.2Hz, 1H), 6.39 (d, J=2.2Hz,
1H),3.91(s,3H),3.89(s,3H).
13C NMR(75MHz,CDCl3): δ 190.7,165.2,164.7,142.7,133.5,133.5,131.2,128.7,
128.6,127.8,116.3,115.8,115.5,103.8,97.3,56.0,55.7.
HRMS (ESI): Found (M+H)+,287.1090.C17H16FO3Calc.(M+H)+,287.1078.
Embodiment 32:(E) preparation of -2- (4- fluorostyryl) -6- hydroxyl -4-methoxybenzaldehyde
Using the product of embodiment 31 as raw material, compound, white solid are obtained in the similar method of embodiment 2
(90%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 12.46 (s, 1H), 10.19 (s, 1H), 7.52-7.45 (m, 2H), 7.41 (d, J
=16.0Hz, 1H), 7.14-7.02 (m, 2H), 6.93 (d, J=15.9Hz, 1H), 6.59 (d, J=2.4Hz, 1H), 6.37 (d,
J=2.4Hz, 1H), 3.87 (s, 3H)
13C NMR(75MHz,CDCl3):δ192.9,166.7,166.3,144.2,134.5,132.6,128.7,128.6,
122.8,116.2,115.9,112.5,107.2,100.1,55.8.
HRMS(ESI):Found(M+H)+,273.0924.C16H13FO3Calc.(M+H)+,273.0921.
Embodiment 33:(E) -6- (4- fluorostyryl) -2- hydroxyl -4- methoxyl group -3- (isopentene group) benzaldehyde system
It is standby
Using the product of embodiment 32 as raw material, compound, yellow solid are obtained in the similar method of embodiment 3
(40%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3):δ12.43(s,1H),10.18(s,1H),7.53–7.37(m,3H),7.07(t,J
=8.6Hz, 2H), 6.89 (d, J=16.0Hz, 1H), 6.58 (s, 1H), 5.22 (td, J=6.4,5.8,3.5Hz, 1H), 3.95
(s, 3H), 3.36 (d, J=7.1Hz, 2H), 1.80 (s, 3H), 1.69 (s, 3H)
13C NMR(75MHz,CDCl3):δ193.1,164.5,163.8,162.3,161.2,142.2,133.8,132.7,
132.7,132.1,128.5,128.4,123.3,123.2,121.7,116.8,116.0,115.7,112.7,101.8,25.8,
21.5,17.8.
HRMS(ESI):Found(M+H)+,341.1561.C21H21FO3Calc.(M+H)+,341.1547.
Embodiment 34:(E) -3- (4- fluorostyryl) -2- formoxyl -5- methoxyl group -6- (isopentene group) phenylacetic acid
The preparation of ester
Using the product of embodiment 33 as raw material, compound, yellow solid are obtained in the similar method of embodiment 4
(99%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 10.20 (s, 1H), 7.76 (d, J=16.1Hz, 1H), 7.50 (dd, J=8.6,
5.5Hz, 2H), 7.06 (t, J=8.6Hz, 2H), 6.94 (s, 1H), 6.89 (d, J=16.1Hz, 1H), 5.09 (tt, J=7.0,
1.4Hz, 1H), 3.96 (s, 3H), 3.26 (d, J=7.0Hz, 2H), 2.39 (s, 3H), 1.76 (s, 3H), 1.68 (s, 3H)
13C NMR(75MHz,CDCl3):δ188.7,169.5,162.2,151.5,141.7,133.2,133.0,132.6,
128.7,128.6,125.5,123.4,121.0,119.2,116.0,115.7,107.0,56.1,25.8,23.1,20.9,
17.9.
HRMS(ESI):Found(M+H)+,383.1653.C23H23FO4Calc.(M+H)+,383.1653.
Embodiment 35:(E) -2- acetoxyl group -6- (4- fluorostyryl) -4- methoxyl group -3- (isopentene group) benzoic acid
Preparation
Using the product of embodiment 34 as raw material, compound, white solid are obtained in the similar method of embodiment 5
(88%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 7.56-7.42 (m, 3H), 7.07-6.98 (m, 3H), 6.95 (d, J=
16.1Hz, 1H), 5.11 (ddt, J=7.1,3.1,1.6Hz, 1H), 3.95 (s, 3H), 3.27 (d, J=7.0Hz, 2H), 2.30
(s, 3H), 1.75 (d, J=1.3Hz, 3H), 1.69 (d, J=1.3Hz, 3H)
13C NMR(75MHz,CDCl3):δ171.8,169.5,160.4,149.1,138.5,133.3,132.4,130.6,
128.6,128.5,126.8,123.6,121.1,116.1,115.9,115.6,106.2,56.0,25.8,23.5,20.9,
17.9.
HRMS(ESI):Found(M-H)-,397.1456.C23H23FO5Calc.(M+H)+,397.1457.
Embodiment 36:(E) -6- (4- fluorostyryl) -2- hydroxyl -4- methoxyl group -3- (isopentene group) benzoic acid system
It is standby
Using the product of embodiment 35 as raw material, compound, white solid are obtained in the similar method of embodiment 6
(97%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,Acetone-d6): δ 7.94 (d, J=16.1Hz, 1H), 7.67-7.54 (m, 2H), 7.14
(t, J=8.8Hz, 2H), 7.00 (d, J=16.0Hz, 1H), 6.84 (s, 1H), 5.21 (tdd, J=5.8,2.9,1.4Hz,
1H), 3.97 (s, 3H), 3.35 (d, J=7.3Hz, 2H), 1.77 (s, 3H), 1.64 (s, 3H)
13C NMR(75MHz,Acetone-d6):δ174.2,163.0,162.4,141.7,135.2,135.2,131.6,
131.2,129.9,129.4,129.3,123.2,116.9,116.5,116.2,104.8,103.4,56.2,25.9,22.7,
17.9.
HRMS(ESI):Found(M-H)-,355.1359.C21H21FO4Calc.(M+H)+,355.1351.
Embodiment 37:(E) -2,4- dimethoxy -6- (4- methoxyl-styrene) benzaldehyde preparation
Using 4- methoxy styrene as starting material, compound, white solid are obtained in the similar method of embodiment 1
(82%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 10.53 (s, 1H), 8.06 (d, J=16.2Hz, 1H), 7.50 (d, J=
8.7Hz, 2H), 6.97 (d, J=16.2Hz, 1H), 6.89 (d, J=8.7Hz, 2H), 6.74 (d, J=2.2Hz, 1H), 6.37
(d, J=2.2Hz, 1H), 3.91 (s, 3H), 3.88 (s, 3H), 3.83 (s, 3H)
13C NMR(75MHz,CDCl3):δ190.8,165.1,164.6,159.7,143.3,132.3,130.1,128.5,
125.6,116.2,114.2,103.4,97.0,56.0,55.7,55.4.
HRMS(ESI):Found(M+H)+,299.1278.C18H19O4Calc.(M+H)+,299.1283.
Embodiment 38:(E) -2- hydroxyl -4- methoxyl group -6- (4- methoxyl-styrene) benzaldehyde preparation
Using the product of embodiment 37 as raw material, compound, white solid are obtained in the similar method of embodiment 2
(93%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 12.48 (s, 1H), 10.19 (s, 1H), 7.44 (d, J=8.7Hz, 2H), 7.35
(d, J=15.9Hz, 1H), 6.93 (d, J=15.9Hz, 1H), 6.92 (d, J=8.7Hz, 2H), 6.59 (d, J=2.3Hz,
1H), 6.34 (d, J=2.3Hz, 1H), 3.87 (s, 3H), 3.84 (s, 3H)
13C NMR(75MHz,CDCl3):δ193.0,166.7,166.2,160.2,144.8,135.2,129.2,128.4,
120.5,114.4,112.4,106.7,99.7,55.8,55.5.
HRMS(ESI):Found(M+H)+,285.1122.C17H16O4Calc.(M+H)+,285.1121.
Embodiment 39:(E) -2- hydroxyl -4- methoxyl group -6- (4- methoxyl-styrene) -3- (isopentene group) benzaldehyde
Preparation
Using the product of embodiment 38 as raw material, compound, white solid are obtained in the similar method of embodiment 3
(43%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 12.43 (s, 1H), 10.21 (s, 1H), 7.45 (d, J=8.7Hz, 2H), 7.39
(d, J=15.9Hz, 1H), 6.92 (d, J=8.7Hz, 2H), 6.89 (d, J=15.9Hz, 1H), 6.59 (s, 1H), 5.22 (tt,
J=7.2,1.4Hz, 1H), 3.95 (s, 3H), 3.84 (s, 3H), 3.35 (d, J=7.2Hz, 2H), 1.80 (s, 3H), 1.69 (s,
4H).
13C NMR(75MHz,CDCl3):δ193.3,163.8,162.3,160.1,142.9,134.7,132.1,129.3,
128.2,121.8,121.2,116.4,114.4,112.8,101.7,55.9,55.4,25.9,21.6,17.9.
HRMS(ESI):Found(M+H)+,353.1747.C22H24O4Calc.(M+H)+,353.1747.
Embodiment 40:(E) -2- formoxyl -5- methoxyl group -3- (4- methoxyl-styrene) -6- (isopentene group) phenyl
The preparation of acetic acid esters
Using the product of embodiment 39 as raw material, compound, white solid are obtained in the similar method of embodiment 4
(97%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 10.22 (s, 1H), 7.68 (d, J=16.0Hz, 1H), 7.47 (d, J=
8.7Hz, 2H), 6.97-6.84 (m, 4H), 5.09 (tdd, J=5.6,2.9,1.4Hz, 1H), 3.96 (s, 3H), 3.83 (s,
3H), 3.26 (d, J=7.0Hz, 2H), 2.40 (s, 3H), 1.75 (s, 3H), 1.68 (s, 3H)
13C NMR(75MHz,CDCl3):δ188.7,169.6,162.1,160.0,151.1,142.5,134.3,132.5,
129.6,128.4,123.1,123.0,121.1,119.0,114.3,106.8,56.1,55.5,25.8,23.0,20.9,
17.9.
HRMS(ESI):Found(M+H)+,395.1852.C24H26O5Calc.(M+H)+,395.1853.
Embodiment 41:(E) -2- acetoxyl group -4- methoxyl group -6- (4- methoxyl-styrene) -3- (isopentene group) benzene
The preparation of formic acid
Using the product of embodiment 40 as raw material, compound, white solid are obtained in the similar method of embodiment 4
(89%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 7.50-7.40 (m, 3H), 7.04 (s, 1H), 6.95 (d, J=16.0Hz, 1H),
6.88 (d, J=8.7Hz, 2H), 5.16-5.04 (m, 1H), 3.95 (s, 3H), 3.81 (s, 3H), 3.25 (d, J=7.0Hz,
2H),2.30(s,3H),1.74(s,3H),1.68(s,3H).
13C NMR(75MHz,CDCl3):δ171.6,169.5,160.3,159.7,149.0,138.8,132.3,131.4,
129.9,128.3,124.7,123.1,121.2,116.0,114.3,105.9,56.0,55.4,25.9,23.5,21.0,
17.9.
HRMS(ESI):Found(M-H)-,409.1657.C24H26O6Calc.(M-H)-,409.1657.
Embodiment 42:(E) -2- hydroxyl -4- methoxyl group -6- (4- methoxyl-styrene) -3- (isopentene group) benzoic acid
Preparation
Using the product of embodiment 41 as raw material, compound, white solid are obtained in the similar method of embodiment 5
(98%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,Acetone-d6): δ 12.30 (s, 1H), 7.87 (d, J=16.0Hz, 1H), 7.50 (d, J=
8.7Hz, 2H), 7.02-6.91 (m, 3H), 6.84 (s, 1H), 5.21 (ddt, J=8.8,7.3,1.5Hz, 1H), 3.97 (s,
3H), 3.82 (s, 3H), 3.34 (d, J=7.3Hz, 2H), 1.81-1.72 (m, 3H), 1.63 (d, J=1.4Hz, 3H)
13C NMR(75MHz,Acetone-d6):δ171.4,160.0,159.5,157.6,139.3,128.5,128.4,
128.0,125.9,125.9,120.4,113.5,112.0,101.8,100.2,53.2,52.7,28.8,23.0,19.7,
15.0.
HRMS(ESI):Found(M-H)-,367.1549.C22H24O5Calc.(M-H)-,367.1551.
The cajanin analog that the double bond that the cajanin analog and isopentene group of double bond reduction are replaced by geranyl restores
Synthesis.
The preparation of embodiment 43:2,4- dimethoxy -6- phenethyl benzaldehyde
It using the compound that embodiment 1 obtains as raw material, is dissolved in ethyl acetate, 10% palladium carbon is added, then hydrogen
Balloon effect lower reaction 18 hours, suction filtered through kieselguhr, ethyl acetate washing, it was that product (is received that compound is obtained under vacuum distillation
Rate is that 100%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 10.53 (d, J=1.0Hz, 1H), 7.40-7.23 (m, 4H), 7.24-7.15
(m, 1H), 6.35 (d, J=2.3Hz, 1H), 6.23 (d, J=2.3Hz, 1H), 3.89 (s, 3H), 3.80 (s, 3H), 3.36-
3.19 (t, J=7.5Hz, 2H), 2.92-2.81 (t, J=7.5Hz, 2H)
13C NMR(75MHz,CDCl3):δ190.3,165.6,164.6,148.3,142.2,128.8,128.3,125.9,
116.9,108.4,96.3,55.9,55.5,37.6,37.3.
HRMS(ESI):Found(M+H)+,271.1335.C17H18O3Calc.(M+H)+,271.1329.
The preparation of embodiment 44:2- hydroxyl -4- methoxyl group -6- phenethyl benzaldehyde
Using the product of embodiment 43 as raw material, compound, white solid are obtained in the similar method of embodiment 2
(90%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3):δ12.53(s,1H),10.01(s,1H),7.41-7.23(m,5H),7.22-
7.09(m,3H),6.43-6.05(m,3H),3.84(s,4H),3.43-3.06(m,2H),3.05-2.89(m,2H).
13C NMR(75MHz,CDCl3):δ192.5,166.8,166.7,147.8,140.5,128.7,128.5,126.6,
112.6,109.9,99.0,55.7,38.7,33.9.
HRMS(ESI):Found(M+H)+,257.1183.C16H16O3Calc.(M+H)+,257.1172.
The preparation of embodiment 45:2- hydroxyl -4- methoxyl group -3- (isopentene group) -6- phenethyl benzaldehyde
Using the product of embodiment 44 as raw material, compound, white solid are obtained in the similar method of embodiment 3
(40%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3):δ12.43(s,1H),10.06(s,1H),7.37–7.23(m,3H),7.19–
7.09 (m, 2H), 6.22 (s, 1H), 5.20 (dddd, J=8.5,5.7,2.8,1.4Hz, 1H), 3.83 (s, 3H), 3.40-3.27
(m, 2H), 3.16 (dd, J=9.2,6.5Hz, 2H), 2.94 (dd, J=9.2,6.5Hz, 2H), 1.79 (d, J=1.3Hz, 3H),
1.69 (d, J=1.4Hz, 3H)
13C NMR(75MHz,CDCl3):δ192.8,163.9,162.8,145.9,140.6,132.0,128.7,128.6,
126.5,122.0,115.5,112.9,104.9,55.8,39.2,34.2,25.9,21.4,17.9.
HRMS(ESI):Found(M+H)+,325.1808.C21H25O3Calc.(M+H)+,325.1798.
The preparation of embodiment 46:2- formoxyl -5- methoxyl group -6- (isopentene group) -3- phenethyl phenylacetic acid ester
Using the product of embodiment 45 as raw material, compound, white solid are obtained in the similar method of embodiment 4
(91%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3):δ10.18(s,1H),7.35–7.26(m,2H),7.25–7.17(m,3H),6.50
(s, 1H), 5.07 (tt, J=7.0,1.5Hz, 1H), 3.82 (s, 3H), 3.33-3.18 (m, 4H), 2.91 (dd, J=9.3,
6.6Hz, 2H), 2.39 (s, 3H), 1.75 (d, J=1.3Hz, 3H), 1.68 (d, J=1.5Hz, 3H)
13C NMR(75MHz,CDCl3):δ188.3,169.5,162.1,152.0,146.0,141.2,132.3,128.7,
128.5,126.2,122.0,121.2,119.3,110.8,56.0,38.3,35.9,25.8,22.9,20.9,17.9.
HRMS(ESI):Found(M+H)+,367.1914.C23H26O4Calc.(M+H)+,367.1904.
The preparation of embodiment 47:2- acetoxyl group -4- methoxyl group -3- (isopentene group) -6- phenethyl benzoic acid
Using the product of embodiment 46 as raw material, compound, white solid are obtained in the similar method of embodiment 5
(86%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 7.30-7.22 (m, 2H), 7.19 (dt, J=8.0,2.0Hz, 3H), 6.52 (s,
1H), 5.09 (tt, J=5.6,1.8Hz, 1H), 3.78 (s, 3H), 3.22 (d, J=7.1Hz, 2H), 3.17-3.07 (m, 2H),
2.95 (dd, J=9.9,6.0Hz, 2H), 2.28 (s, 3H), 1.73 (d, J=1.3Hz, 3H), 1.67 (d, J=1.4Hz, 3H)
13C NMR(75MHz,CDCl3):δ172.0,169.5,160.1,149.0,142.6,141.7,132.1,128.7,
128.5,126.1,121.9,121.5,116.7,110.5,55.9,38.1,37.3,25.8,23.4,21.0,17.9.
HRMS(ESI):Found(M-H)-,381.1697.C23H25O5Calc.(M-H)-,381.1707.
The preparation of embodiment 48:2- hydroxyl -4- methoxyl group -3- (isopentene group) -6- phenethyl benzoic acid
Using the product of embodiment 47 as raw material, compound, white solid are obtained in the similar method of embodiment 6
(96%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3):δ11.60(s,1H),7.38–7.28(m,2H),7.26–7.19(m,3H),6.24
(s, 1H), 5.30-5.16 (m, 1H), 3.81 (s, 3H), 3.37 (d, J=7.1Hz, 2H), 3.34-3.23 (m, 2H), 2.95
(dd, J=9.6,6.3Hz, 2H), 1.81 (d, J=1.3Hz, 3H), 1.71 (d, J=1.5Hz, 3H)
13C NMR(75MHz,CDCl3):δ176.4,163.0,162.3,146.0,142.0,131.9,128.7,128.5,
126.1,122.3,115.5,106.7,103.8,55.7,39.4,38.3,26.0,22.1,17.9.
HRMS(ESI):Found(M-H)-,339.1605.C21H24O4Calc.(M-H)-,339.1602.
Embodiment 49:(E) -3- (geranyl) -2- hydroxyl -4- methoxyl group -6- phenethyl benzaldehyde preparation
It using the product of embodiment 44 as raw material, is dissolved in 50mL toluene, sodium hydride (1~1.5 equivalent) is added at 0 DEG C, room
Temperature stirring 0.5h, is added isoprenyl bromide (1~1.5 equivalent), is warming up to 65 DEG C of reaction 4h, stop reaction, be cooled to room temperature, add
Enter water, separates organic layer, then extracted with ethyl acetate (2 × 50mL), merge organic layer, wash (1 × 100mL), saturated common salt
It washes (1 × 100mL).Anhydrous sodium sulfate dries, filters, and evaporating solvent under reduced pressure obtains yellow oil, silica gel column purification, petroleum
Ether: ethyl acetate=100:1 affords compound, yellow oily liquid (43%), and following characterize data illustrates successfully to synthesize
Target product.
1H NMR(300MHz,CDCl3):δ12.47(s,1H),10.09(s,1H),7.37–7.25(m,4H),7.20–
7.14 (m, 2H), 6.25 (s, 1H), 5.23 (q, J=1.3Hz, 1H), 5.11 (tt, J=5.5,3.1Hz, 1H), 3.86 (s,
3H), 3.36 (d, J=7.1Hz, 2H), 3.24-3.15 (m, 2H), 2.98 (d, J=8.6Hz, 2H), 2.14-2.05 (m, 3H),
2.05-1.96 (m, 3H), 1.82 (d, J=1.3Hz, 3H), 1.69 (d, J=1.3Hz, 3H), 1.62 (d, J=1.3Hz, 3H)
13C NMR(75MHz,CDCl3):δ192.7,163.9,162.8,145.8,140.6,135.4,131.2,128.6,
128.5,126.5,124.5,121.8,115.5,112.8,104.8,55.8,39.9,39.2,34.2,26.8,25.8,21.3,
17.8,16.2.
HRMS(ESI):Found(M+H)+,393.2433.C26H32O3Calc.(M+H)+,393.2424.
Embodiment 50:(E) -2- (geranyl) -6- formoxyl -3- methoxyl group -5- phenethyl phenylacetic acid ester preparation
Using the product of embodiment 49 as raw material, compound, white solid are obtained in the similar method of embodiment 4
(96%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 10.19 (s, 1H), 7.35-7.25 (m, 2H), 7.22 (d, J=7.0Hz, 3H),
6.50 (s, 1H), 5.08 (ddd, J=6.9,5.4,2.9Hz, 2H), 3.81 (s, 3H), 3.33-3.19 (m, 4H), 2.92 (dd, J
=9.3,6.6Hz, 2H), 2.38 (s, 3H), 2.07 (q, J=7.6,6.4Hz, 2H), 2.01-1.92 (m, 2H), 1.75 (d, J=
1.4Hz, 3H), 1.66 (d, J=1.4Hz, 3H), 1.59 (d, J=1.3Hz, 3H)
13C NMR(75MHz,CDCl3):δ188.3,169.5,162.1,152.1,145.9,141.2,135.9,131.4,
128.7,128.5,126.2,124.3,122.1,121.2,119.3,110.8,55.9,39.7,38.2,35.8,26.7,
25.8,22.8,20.8,17.8,16.2.
HRMS(ESI):Found(M+H)+,435.2536.C28H34O4Calc.(M+H)+,435.2535.
Embodiment 51:(E)-2- acetoxy-3-(geranyl)-4- methoxyl group-6- phenethyl benzoic acid preparation
Using the product of embodiment 50 as raw material, compound, white solid are obtained in the similar method of embodiment 5
(86%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3):δ7.31–7.24(m,2H),7.23–7.15(m,3H),6.54(s,1H),5.17–
5.02 (m, 2H), 3.79 (s, 3H), 3.25 (d, J=6.9Hz, 2H), 3.14 (dd, J=9.5,5.7Hz, 2H), 2.97 (dd, J
=9.9,6.1Hz, 2H), 2.29 (s, 3H), 2.06 (s, 2H), 1.99 (d, J=7.2Hz, 2H), 1.74 (d, J=1.3Hz,
3H), 1.69-1.63 (m, 3H), 1.60 (d, J=1.3Hz, 3H)
13C NMR(75MHz,CDCl3):δ172.1,169.5,160.1,149.1,142.5,141.7,135.6,131.4,
128.7,128.5,126.1,124.4,122.0,121.4,116.7,110.4,55.8,39.8,38.1,37.3,26.8,
25.8,23.2,20.9,17.8,16.2.
HRMS(ESI):Found(M-H)-,449.2324.C28H33O5Calc.(M-H)-,449.2333.
Embodiment 52:(E) -3- (geranyl) -2- hydroxyl -4- methoxyl group -6- phenethyl benzoic acid preparation
Using the product of embodiment 51 as raw material, compound, white solid are obtained in the similar method of embodiment 6
(98%), following characterize data explanation successfully synthesizes target product.
1H NMR(300MHz,CDCl3): δ 11.60 (s, 1H), 7.31 (dd, J=7.9,6.8Hz, 2H), 7.23 (d, J=
7.0Hz, 3H), 6.24 (s, 1H), 5.22 (tt, J=5.7,3.2Hz, 1H), 5.09 (tt, J=5.5,2.6Hz, 1H), 3.80
(s, 3H), 3.38 (d, J=7.1Hz, 2H), 3.33-3.22 (m, 2H), 2.95 (dd, J=9.6,6.3Hz, 2H), 2.07 (t, J
=7.4Hz, 2H), 1.99 (dd, J=9.6,5.0Hz, 3H), 1.81 (d, J=1.3Hz, 3H), 1.66 (d, J=1.3Hz, 3H),
1.59 (d, J=1.3Hz, 3H)
13C NMR(75MHz,CDCl3):δ176.4,163.0,162.3,146.0,142.0,135.3,131.3,128.7,
128.5,126.1,124.6,122.1,115.6,106.7,103.8,55.7,40.0,39.4,38.3,26.9,25.8,22.0,
17.8,16.3.
HRMS(ESI)Found(M-H)-,407.2216.C26H32O4Calc.(M-H)-,407.2228.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (10)
1. the preparation method of a kind of cajanin and its analogue, it is characterised in that (1)~(4) in including the following steps,
(1)~(5), (1)~(6) or (1)~(7):
(1) with the bromo- 3,5- dimethoxy benzene of 1-, formylation obtains the bromo- 4,6- dimethoxy of 2- at DMF and phosphorus oxychloride effect
Benzaldehyde；
(2) under catalyst and alkali existence condition, by bromo- 4, the 6- dimethoxy benzaldehyde of obtained 2- and R1Substituted benzene second
Alkene carries out Heck coupling reaction in a solvent and obtains 2,4- dimethoxy -6-R1Substituted phenylethylene benzaldehyde；
(3) under reaction dissolvent existence condition, using demethylation reagent to 2,4- dimethoxy -6-R1Substituted phenylethylene Ji Benjia
Aldehyde carries out selective demethylation and obtains 2- hydroxyl -4- methoxyl group -6-R1Substituted phenylethylene benzaldehyde；
(4) 2- hydroxyl -4- methoxyl group -6-R1Substituted phenylethylene benzaldehyde obtains (E) -2- hydroxyl -4- by C- isopentene group
Methoxyl group -3- (isopentene group) -6-R1Substituted phenylethylene benzaldehyde；
(5) (E) -2- hydroxyl -4- methoxyl group -3- (isopentene group) -6-R1Substituted phenylethylene benzaldehyde is protected to obtain through acetyl group
(E)-3-(R1Substituted phenylethylene base) -2- formoxyl -5- methoxyl group -6- (isopentene group) phenylacetic acid ester；
(6)(E)-3-(R1Substituted phenylethylene base) -2- formoxyl -5- methoxyl group -6- (isopentene group) phenylacetic acid ester aldehyde radical warp
Pinnick aoxidizes to obtain carboxyl compound (E) -2- acetoxyl group -6- (R1Substituted phenylethylene base) -4- methoxyl group -3- (iso-amylene
Base) benzoic acid；
(7) by (E) -2- acetoxyl group -6- (R1Substituted phenylethylene base) -4- methoxyl group -3- (isopentene group) benzoic acid deacetylation
Protection, obtains (E) -6- (R1Substituted phenylethylene base) -2- hydroxyl -4- methoxyl group -3- (isopentene group) benzoic acid；
Alternatively,
It further include step of hydrogenation between step (3) and step (4), step of hydrogenation is the method for hydrogenation of this field routine.
2. the preparation method of cajanin analogue according to claim 1, it is characterised in that: step (4) replacement are as follows:
2- hydroxyl -4- methoxyl group -6-R1Substituted phenylethylene benzaldehyde obtains (E) -2- hydroxyl -4- methoxyl group -3- by geranylgeranylation
(geranyl) -6-R1Substituted phenylethylene benzaldehyde.
3. the preparation method of cajanin according to claim 1 or 2 and its analogue, it is characterised in that:
The reaction temperature of formylation described in step (1) is 25~100 DEG C, and the reaction time is 4~12h；1- used is bromo-
The dosage of 3,5- dimethoxy benzene, DMF and phosphorus oxychloride meets mole of the bromo- 3,5- dimethoxy benzene of 1-, DMF and phosphorus oxychloride
Than for 1:6:3.
4. the preparation method of cajanin according to claim 1 or 2 and its analogue, it is characterised in that:
Catalyst described in step (2) is divalent or zero valent palladium catalyst, and the amount of catalyst is catalytic amount；The alkali is phosphorus
Sour potassium, the dosage of potassium phosphate are 1~3 times of bromo- 4, the 6- dimethoxy benzaldehyde mole of 2-；The solvent is the non-matter of polarity
Sub- property solvent；
The temperature of Heck coupling reaction described in step (2) be 100~160 DEG C, the reaction time be 3~for 24 hours；The 2,4-
Dimethoxy -6- bromobenzaldehyde and R1The dosage of substituted styrene meets 2,4- dimethoxy -6- bromobenzaldehyde and R1Replace
The molar ratio of styrene is 1:1~5.
5. the preparation method of cajanin according to claim 1 or 2 and its analogue, it is characterised in that:
Reaction dissolvent described in step (3) is hydrocarbon solvent；The demethylation reagent is Lewis acidic reagents；Described
Selective demethylation refers to carry out at -80 DEG C~25 DEG C, and the progress time is 1~12h；Demethylation reagent used, 2,4- bis-
Methoxyl group -6-R1The dosage of substituted phenylethylene benzaldehyde meets demethylation reagent and 2,4- dimethoxy -6-R1Substituted phenylethylene
The molar ratio of benzaldehyde is 1~2:1.
6. the preparation method of cajanin according to claim 1 and its analogue, it is characterised in that:
C- isopentene group described in step (4) refers to 2- hydroxyl -4- methoxyl group -6-R1Substituted phenylethylene benzaldehyde is molten
The iso-amylene glycosylation reaction of aryl occurs under agent and alkaline condition with isopentene group reagent；
Wherein, the solvent is aromatic hydrocarbons；The alkaline condition refers to that alkali, which is added, creates alkaline condition, wherein the dosage of alkali
For 2- hydroxyl -4- methoxyl group -6-R11~1.5 times of substituted phenylethylene benzaldehyde mole；The isopentene group reagent
For halogenated iso-amylene or the sulphonic acid ester of isopentene group；2- hydroxyl -4- methoxyl group-the 6-R1Substituted phenylethylene base benzene
The molar ratio of formaldehyde and isopentene group reagent is 1:1~1.5；The iso-amylene glycosylation reaction of the aryl refers to 50~
110 DEG C of 2~5h of reaction.
7. the preparation method of cajanin according to claim 2 and its analogue, it is characterised in that:
Geranylgeranylation described in step (4) refers to 2- hydroxyl -4- methoxyl group -6-R1Substituted phenylethylene benzaldehyde in solvent and
The geranylgeranylation that aryl occurs with geranylgeranylation reagent under alkaline condition reacts；
Wherein, the solvent is aromatic hydrocarbons；The alkaline condition refers to that alkali, which is added, creates alkaline condition, wherein the dosage of alkali
For 2- hydroxyl -4- methoxyl group -6-R11~1.5 times of substituted phenylethylene benzaldehyde mole；The geranylgeranylation reagent is
Halogenated geranyl；2- hydroxyl -4- methoxyl group-the 6-R1The molar ratio of substituted phenylethylene benzaldehyde and geranylgeranylation reagent
For 1:1~1.5；The geranylgeranylation reaction of the aryl refers in 50~110 DEG C of 2~5h of reaction.
8. the preparation method of cajanin according to claim 1 or 2 and its analogue, it is characterised in that:
The protection of acetyl group described in step (5) refers specifically to (E) -2- hydroxyl -4- methoxyl group -3- (iso-amylene under alkaline condition
Base) -6-R1Aldehyde radical vicinal hydroxyl groups occur under non-protonic solvent existence condition for substituted phenylethylene benzaldehyde and acylating reagent
Acetylization reaction；
Wherein, the alkaline condition refers to that alkali, which is added, creates alkaline condition, and wherein the dosage of alkali is (E) -2- hydroxyl -4- methoxy
Base -3- (isopentene group) -6-R11~5 times of substituted phenylethylene benzaldehyde mole；The acylating reagent is acyl chlorides, acyl
Bromine or acid anhydrides；The solvent is methylene chloride or chloroform；The aldehyde radical vicinal hydroxyl groups acetylization reaction refers to -10~
25 DEG C of reactions 0.5~for 24 hours；(E) -2- hydroxyl -4- methoxyl group -3- (isopentene group) -6-R used1Substituted phenylethylene Ji Benjia
The dosage of aldehyde and acylating reagent meets (E) -2- hydroxyl -4- methoxyl group -3- (isopentene group) -6-R1Substituted phenylethylene benzaldehyde
Molar ratio with acylating reagent is 1:1~1:5.
9. the preparation method of cajanin according to claim 1 or 2 and its analogue, it is characterised in that:
The oxidation of Pinnick described in step (6) refers to (E) -3- (R1Substituted phenylethylene base) -2- formoxyl -5- methoxyl group -6-
The aldehyde radical of (isopentene group) phenylacetic acid ester is under sodium dihydrogen phosphate and solvent existence condition, with and without 2- methyl -2-
Under butylene protection, acid is oxidized under conditions of sodium chlorite makees oxidant；Wherein solvent refers to the mixed solution of alcohol, ether and water,
The volume of alcohol, ether and water is 1~10:1~10:1~10；(E) -3- (R1Substituted phenylethylene base) -2- formoxyl -5- first
Oxygroup -6- (isopentene group) phenylacetic acid ester, sodium dihydrogen phosphate, 2- methyl-2-butene and sodium chlorite molar ratio be 1:2~
10:2~100:2~10.
10. the preparation method of cajanin according to claim 1 or 2 and its analogue, it is characterised in that:
The protection of deacetylation described in step (7) refers to (E) -2- acetoxyl group -6- (R1Substituted phenylethylene base) -4- methoxyl group -
3- (isopentene group) benzoic acid in a solvent, protect by hydrolyzed under basic conditions deacetylation；Wherein solvent is methanol, ethyl alcohol or four
Hydrogen furans；Alkaline condition refers to that sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate, which is added, creates alkaline condition.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111423325A (en) * | 2020-04-26 | 2020-07-17 | 江苏凯迪恩医药科技有限公司 | Synthetic method of diacerein based on anthraquinone drugs |
| CN114075107A (en) * | 2020-08-17 | 2022-02-22 | 暨南大学 | Cajanin derivatives and application thereof in preparation of antibacterial drugs |
| CN114591136A (en) * | 2022-03-21 | 2022-06-07 | 西安瑞联新材料股份有限公司 | Synthetic method of 2-phenylanthracene |
| CN115536497A (en) * | 2022-11-23 | 2022-12-30 | 化学与精细化工广东省实验室 | Synthesis method of (E) -3,5-dihydroxy-4-isopropyl stilbene |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102372627A (en) * | 2010-08-18 | 2012-03-14 | 中国医学科学院医药生物技术研究所 | Preparation method of cajanin and substance with similar structure |
| CN103172512A (en) * | 2011-12-23 | 2013-06-26 | 中国医学科学院医药生物技术研究所 | Cajanin compound with similar structures, as well as preparation method and application thereof |
-
2017
- 2017-12-11 CN CN201711304039.2A patent/CN109896943A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102372627A (en) * | 2010-08-18 | 2012-03-14 | 中国医学科学院医药生物技术研究所 | Preparation method of cajanin and substance with similar structure |
| CN103172512A (en) * | 2011-12-23 | 2013-06-26 | 中国医学科学院医药生物技术研究所 | Cajanin compound with similar structures, as well as preparation method and application thereof |
| CN105030750A (en) * | 2011-12-23 | 2015-11-11 | 中国医学科学院医药生物技术研究所 | Application of longistyline structural analogues in prevention of hepatitis C virus and acquired immune deficiency syndrome (AIDS) virus |
Non-Patent Citations (2)
| Title |
|---|
| RACHELLE QUACH ET AL: ""Total Synthesis of the Resorcyclic Acid Lactone Spiroketal Citreoviranol"", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
| YUE HU ET AL: ""Palladium-Catalyzed Ring-Forming Aminoalkenylation of Alkeneswith Aldehydes Initiated by Intramolecular Aminopalladation"", 《ANGEW.CHEM.INT.ED》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111423325A (en) * | 2020-04-26 | 2020-07-17 | 江苏凯迪恩医药科技有限公司 | Synthetic method of diacerein based on anthraquinone drugs |
| CN114075107A (en) * | 2020-08-17 | 2022-02-22 | 暨南大学 | Cajanin derivatives and application thereof in preparation of antibacterial drugs |
| CN114591136A (en) * | 2022-03-21 | 2022-06-07 | 西安瑞联新材料股份有限公司 | Synthetic method of 2-phenylanthracene |
| CN114591136B (en) * | 2022-03-21 | 2024-03-26 | 西安瑞联新材料股份有限公司 | Synthesis method of 2-phenyl anthracene |
| CN115536497A (en) * | 2022-11-23 | 2022-12-30 | 化学与精细化工广东省实验室 | Synthesis method of (E) -3,5-dihydroxy-4-isopropyl stilbene |
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