CN102391079A - Method for preparing chiral biphenyl cyclooctadiene lignan compound - Google Patents
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Abstract
The invention relates to a method for preparing a chiral biphenyl cyclooctadiene lignan compound. The method comprises the following steps of: reacting alkoxy biphenyldicarboxylic acid serving as a raw material with chiral alkamine to form bis-(oxazolinyl)biphenyl; converting an isomer under the action of cuprous iodide, and crystallizing to obtain a specific configurational isomer; and hydrolyzing, performing the protection of acetic anhydride, reducing and bromating further to obtain a biphenyl cyclooctadiene ring with succinate, and reducing by carbethoxy and the like to obtain the configurational biphenyl cyclooctadiene compound, wherein a structural formula of the product is shown in the description. The method has a simple route, few reaction steps, is low in cost and is suitable for large-scale production, raw materials are readily available, and the chiral biphenyl cyclooctadiene lignan compound is easy to prepare.
Description
Technical field
The invention belongs to the organic synthesis field, be specifically related to a kind of compound method of chirality couplet benzene ring octadiene Lignanoids compounds.
Background technology
Lignanoid's composition in the shizandra berry has alt-reducing and liver-protecting, protection cns, anti-HIV, anti-HBV, multiple biological activity such as antitumor.Modern pharmacological research shows; The couplet benzene ring octadiene Lignanoids compounds is the main bioactive ingredients in the shizandra berry; Distinctive biological activity of shizandra berry and skeleton structure are exciting people to explore its effective compound method always, or are guide with it, design, synthetic new similar compound.Discover that the biphenyl structural of natural couplet benzene ring octadiene compound all has specific chiral configuration, its configuration is extremely crucial to its activity.
At present, people are to the synthetic extensive studies of also having launched of couplet benzene ring octadiene compound.In order to obtain the couplet benzene ring octadiene compound of particular configuration, the structure of axle chiral centre is that synthetic is crucial.Usually utilize chiral auxiliary group, the chiral catalyst difference is to selective reaction etc., and forms a chirality through intermolecular or intramolecularly coupling, so more further reaction obtain target compound.But the chiral reagent that the aforesaid method ubiquity is selected for use is relatively more expensive mostly, reaction conditions defective such as harshness too, is not suitable for large-scale production.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of easy relatively chirality couplet benzene ring octadiene Lignanoids compounds.
For realizing above-mentioned purpose, the present invention adopts following technical scheme:
A kind of preparation method of chirality couplet benzene ring octadiene Lignanoids compounds, it comprises the steps:
(1) with the compound a be raw material, methylene dichloride or trichloromethane are solvent, and under the thionyl chloride effect, reflux 5-10h obtains product b after steaming desolventizes, and wherein the mol ratio of thionyl chloride and compound a is 2-15:1; R in the structural formula of compound a
1=R
2=R
3=R
4=Me, perhaps R
1=R
2=Me, R
3+ R
4=CH
2, perhaps R
1+ R
2=R
3+ R
4=CH
2
(2) product b is dissolved in (effect of methylene dichloride is as solvent with lysate in the methylene dichloride; Down together); Under condition of ice bath, it is joined in the dichloromethane solution that contains triethylamine and chiral amino alcohol then; Add back room temperature reaction 2-15h, reaction product changes in the water, through extraction, washing, dry and concentrate product c; Wherein the mol ratio of triethylamine and product b is 2-5:1, and the mol ratio of chiral amino alcohol and product b is 2-4:1;
(3) product c is dissolved in the methylene dichloride; Add triethylamine and 4-Dimethylamino pyridine; Under condition of ice bath, add the dichloromethane solution that is dissolved with Tosyl chloride then, add back room temperature reaction 10-30h, reaction product is through washing, the dry and concentrated and purified product d that gets; Wherein the mol ratio of triethylamine and product c is 2-5:1, and the mol ratio of 4-Dimethylamino pyridine and product c is 0.01-0.05:1, and the mol ratio of Tosyl chloride and product c is 2-4:1;
(4) product d is dissolved in the N (DMF); The cuprous iodide of mol ratios such as adding and product d; Under the protection of inert gas, reflux 50-65h (temperature 150-160 ℃) steams then and removes DMF; Be cooled to room temperature and use dichloromethane extraction, extraction liquid is through washing, the dry and concentrated and purified product e that gets;
(5) product e is dissolved in THF, adds SODIUM SULPHATE ANHYDROUS 99PCT, water and trifluoroacetic acid, room temperature reaction 2-10h, reaction product is through dry, the concentrated product f that obtains; Wherein the mol ratio of SODIUM SULPHATE ANHYDROUS 99PCT and water and product e is 10-50:1, and the mol ratio of trifluoroacetic acid and product e is 2-4:1;
(6) product f is dissolved in the methylene dichloride, adds room temperature reaction 15-25h behind aceticanhydride and the pyridine, add methyl alcohol or ethanol synthesis 0.5-10h (being used for and excessive aceticanhydride reaction) then, reaction product is through washing, dry and concentrated product g; Wherein the mol ratio of aceticanhydride and product f is 2-20:1, and the mol ratio of pyridine and product f is 5-40:1, and methyl alcohol or ethanol and aceticanhydride mol ratio are 1-4:1;
(7) product g is dissolved among the THF; Add lithium aluminum hydride and react 5-8h in-10-0 ℃; Add the excessive acetic acid ethyl ester then and make remaining lithium aluminum hydride react completely (getting final product to no longer producing bubble); Reaction product with dichloromethane extraction after, through washing, dry and concentrated and purified after product h; Wherein the mol ratio of lithium aluminum hydride and product g is 1-10:1;
(8) product h is dissolved in the methylene dichloride, adds phosphorus tribromide under the condition of ice bath and react 1h, room temperature continues reaction 5-10h then, and reaction product is isolated organic layer, through washing, dry and concentrate product i; Wherein the mol ratio of phosphorus tribromide and product h is 1-3:1;
(9) in reaction flask, add THF and diisopropylamine under the protection of inert gas condition; Under condition of ice bath, add n-Butyl Lithium reaction 20-40min then; Then with reaction flask in-add methyl-succinate or diethyl succinate reaction 1-2h after 100--40 ℃ (preferred-78 ℃) places 1-2h; Add the THF solution reaction 1-3h that is dissolved with product i again, then in room temperature reaction 1-5h, reaction product is through extraction, washing, the dry and concentrated and purified product j that gets; Wherein the mol ratio of diisopropylamine and product i is 2-5:1, and n-Butyl Lithium is identical with the addition of diisopropylamine, the mol ratio 1:1 of methyl-succinate or diethyl succinate and product i;
(10) product j is dissolved in the THF; Add lithium aluminum hydride and react 0.5-10h in-10-0 ℃; Add the excessive acetic acid ethyl ester then remaining lithium aluminum hydride reacted completely, reaction product with dichloromethane extraction after, through washing, dry and concentrated and purified after product k; Wherein the mol ratio of lithium aluminum hydride and product j is 1-10:1;
(11) product k is dissolved in the anhydrous pyridine, adds Tosyl chloride reaction 10-15h under the condition of ice bath, reaction product obtains compound l through washing, extraction, drying with after concentrating; Wherein the mol ratio of Tosyl chloride and product k is 2-10:1;
(12) Peng Qinghuana and product l are dissolved in room temperature reaction 1h in the methyl-sulphoxide; Be warming up to 40-50 ℃ of reaction 5-8h then; Be cooled to room temperature and change in the mixture of ice and water, through ethyl acetate extraction, drying and the concentrated and purified title product chirality couplet benzene ring octadiene Lignanoids compounds m that obtains
1Or m
2Wherein the mol ratio of Peng Qinghuana and product l is 2-10:1; Concrete synthetic route is following:
Preferably, the chiral amino alcohol of being selected for use in the step (2) comprises L-amino alcohol and R-amino alcohol (like L-aminopropanol, L-valerian ammonia alcohol, R-aminopropanol or R-valerian ammonia alcohol etc.).
In said synthesis route, substituent R is H, Me, CH in the structural formula of compound c
2Ph, i-Pr, CH (CH
3)
2Or amino alcohol such as i-Bu; Substituent R in the structural formula of compound j '=Me or Et etc.
The inventive method is with 4,5,6, and 4 ', 5 ', 6 '-hexa methoxy biphenyl-2,2 ' dioctyl phthalate (is R in the compound a structural formula
1=R
2=R
3=R
4=Me), or 4,5,6,4 '-tetramethoxy-5 ', 6 '-methylene-dioxy biphenyl-2,2 '-dioctyl phthalate (is R in the compound a structural formula
1=R
2=Me, R
3+ R
4=CH
2), or 4,5,4 ', 5 '-two methylene-dioxies 6,6 '-dimethoxy-2,2 '-biphenyl dicarboxylic acid (is R in the compound a structural formula
1+ R
2=R
3+ R
4=CH
2) be raw material; Form bisoxazoline base biphenyl with the chiral amino alcohol reaction; Under the cuprous iodide effect, isomer transforms, and obtains the particular configuration isomer through crystallization more then; Become the couplet benzene ring octadiene ring behind further hydrolysis, aceticanhydride protection, reduction, the bromo with succinate, and then obtain the chirality couplet benzene ring octadiene compound m of particular configuration through ethoxycarbonyl reduction etc.
In the structure of the synthetic ultimate aim product m that obtains, the chirality between two phenyl ring has M or P particular configuration, and this depends primarily on the chiral amino alcohol of being selected for use.For example, if chiral amino alcohol selects for use the L-amino alcohol to prepare product m
1If chiral amino alcohol selects for use the R-amino alcohol to prepare product m
2
What step (1) was carried out is acyl chloride reaction, and wherein raw material a can be symmetric, also can be asymmetric, can obtain through ullmann or Suzike coupling.
The key point of the inventive method is that step (4) product e configuration conversion is the configuration that a chirality is arranged, and the cyclization of step (9) product j octatomic ring.Compare with prior art, compound method raw material of the present invention is easy to get, and route is simple, and reactions step is few, and cost is low, is easy to preparation, is fit to large-scale production.
Embodiment
Below through preferred embodiment compound method of the present invention is done further explain, but protection scope of the present invention is not limited thereto.
Embodiment 1
A kind of preparation method of chirality couplet benzene ring octadiene Lignanoids compounds, it comprises the steps:
(1) (be R in the structural formula filling 10 g (23.7 mmol) compound a
1=R
2=R
3=R
4In=Me) the reaction flask, add 50 ml methylene dichloride, add 20 ml sulfur oxychloride reflux 8h then, steam to desolventize and obtain yellow liquid behind the methylene dichloride and produce
Thing b.
(2) above-mentioned products therefrom b is dissolved in the 30ml methylene dichloride; Under condition of ice bath, it slowly is added drop-wise in the dichloromethane solution that contains 13ml triethylamine and 5.36 g (52.4 mmol) L-valerian ammonia alcohol then, drips back room temperature reaction 10h, reaction product changes in the water; Through twice of dichloromethane extraction (2 * 50 ml); Merge organic layer and wash (2 * 100 ml) twice with Hydrogen chloride then, saturated sodium bicarbonate aqueous solution is washed (2 * 50 ml) twice, saturated common salt washing 1 time; Through anhydrous sodium sulfate drying, Rotary Evaporators gets yellow thick liquid product c after removing solvent under reduced pressure.
(3) above-mentioned products therefrom c is dissolved in the 60ml methylene dichloride; Add triethylamine 12.1 ml (94.8mmol), 4-Dimethylamino pyridine DMAP 250 mg; Under condition of ice bath, slowly drip Tosyl chloride/methylene dichloride mixed solution (be dissolved in the 50ml methylene dichloride and get) then by 8.18g (47.4 mmol) Tosyl chloride; Drip back stirring at room reaction 24h, reaction product changes in the 80ml saturated aqueous ammonium chloride, and organic layer with the saturated salt washing once; Anhydrous sodium sulfate drying; The Rotary Evaporators reduction vaporization concentrates and obtains faint yellow transparent thick liquid, divides pure (petrol ether/ethyl acetate=1/1) to obtain 9g light yellow transparent liquid product d, yield 68% through silicagel column again.
1HNMR?(300MHz,?CDCl
3):δ7.25?(s,1H),?7.15(s,?1H),?4.09(m,?2H),3.93(s,12H?),?3.81(m,?2H),?3.70(s,3H),?3.63(s,3H),?1.55(m,2H),?1.24(m,2H),0.85-0.72(m,12H).?ESI-MS（m/z）557.4?[M+H]
+。HPLC mensuration de:51.5:48.5 (ODS C18column, acetonitrile/water=60/40,0.8ml/min).
(4) get 5.1g (9.16 mmol) product d and be dissolved among the 60 ml DMF, add 1.7g (9.16 mmol) cuprous iodide, reflux 60h under the nitrogen protection; Remove DMF then under reduced pressure, be cooled to room temperature and use the 30ml dichloromethane extraction, extraction liquid is colourless with 5% ammonia scrubbing to ammoniacal liquor layer; Pure water is washed 1 time; Anhydrous sodium sulfate drying, Rotary Evaporators reduction vaporization concentrate the deep yellow thick liquid, through silicagel column purifying (petrol ether/ethyl acetate=1/1) the 3.4g white crystal.HPLC measures de:93:7 (ODS C18 column, acetonitrile/water=60/40,0.8 ml/min).Use ether: sherwood oil/1:2 recrystallization obtains 2.9g white needle-like crystals product e, yield 56.8%. de100%, fusing point: 81-82 ℃, [a]
D 20-31 ° of (c0.8, CHCl
3).
(5) get 2g product e and be dissolved in the 20ml THF; Add 25.5g (180 mmol) SODIUM SULPHATE ANHYDROUS 99PCT, 3.24g (180 mmol) water and 1ml (14.3 mmol) trifluoroacetic acid; Room temperature reaction 10h adds anhydrous magnesium sulfate drying, filtration in the reaction product, concentrating under reduced pressure obtains product f;
(6) above-mentioned products therefrom f is dissolved in the 20ml methylene dichloride; Room temperature reaction 21h behind adding 4.7ml (50mmol) aceticanhydride and 8.1ml (100mmol) pyridine; Add 5ml methyl alcohol stirring at room reaction 1h (being used for making remaining aceticanhydride to react completely) then; Reaction product is given a baby a bath on the third day after its birth time (3 * 20 ml), is washed once with 10% hydrochloric acid successively, and organic phase is lower than 30 ℃ of evaporation concentration and obtains product g through anhydrous sodium sulfate drying;
(7) above-mentioned products therefrom g is dissolved among the 25 ml THF; Add 1 g lithium aluminum hydride and react 8h in 0 ℃; Add the excessive acetic acid ethyl ester then and make remaining lithium aluminum hydride react completely (getting final product to no longer producing bubble); Reaction product with dichloromethane extraction after, organic layer is through Hydrogen chloride washing, anhydrous sodium sulfate drying and concentrating under reduced pressure, behind the silicagel column purifying 1.05g white crystal product h.Fusing point: 106-109 ℃, [a]
D 20+ 34.2 ° (
c1.04, CHCl
3).
1H NMR (300MHz, CDCl
3): δ 6.89 (s, 2H), 4.16 (s, 4H), 3.93-3.88 (d, 12H), 3.67 (s, 6H), 2.73 (s, OH). ee 98.8% (HPLC, chiral OD-H ethanol: normal hexane/20:80,1ml/min).
(8) getting 1g (2.4mmol) product h is dissolved in the 30 ml methylene dichloride; Slowly drip 0.8 ml phosphorus tribromide under the condition of ice bath and react 1h; Room temperature continues reaction 8h then; After reaction finishes reaction solution is changed in 5 ℃ the water, get the organic layer water and be washed till neutrality, anhydrous sodium sulfate drying and concentrating under reduced pressure get 1.08g. white crystal product i; Yield: 81.8%, fusing point 111-112 ℃.
(9) in reaction flask, add 20 ml THF and 0.98 ml diisopropylamine under the nitrogen protection condition, under condition of ice bath, add 2.1ml n-Butyl Lithium reaction 30min then, then reaction flask is slowly added 0.41g diethyl succinate reaction 1.5h behind-78 ℃ of placement 1h; Slowly add THF solution (1.08g product i is dissolved among 6 mlTHF) the reaction 2h that is dissolved with product i again, then in room temperature reaction 5h, reaction finishes the back and pours reaction solution in the 1N hydrochloric acid into; With twice of dichloromethane extraction (2 * 15 ml); Wash 1 time, saturated sodium bicarbonate aqueous solution is washed 1 time, saturated common salt washing 1 time; Organic layer is used anhydrous sodium sulfate drying; Concentrating under reduced pressure, (sherwood oil: ETHYLE ACETATE/2:1) purifying obtains 0.98g colourless viscous liquid product j, yield 89.0% to silicagel column.[a]
D ?20?-92°(
c?0.52,?CH
2Cl
2?)，
1HNMR(300MHz,?CDCl
3):?δ6.66-6.51(s,?2H),?4.17-4.01(m,?4H),?3.83(s,?12H)?,?3.54(s,?6H?),?3.31(d,?2H),?3.06(m,?2H),?2.83(d,?2H),?1.21(m,?6H)。
(10) getting 0.5 g product j is dissolved in the 15 ml THFs; Add 0.3 g lithium aluminum hydride and react 7h in 0 ℃; Adding the excessive acetic acid ethyl ester then reacts completely remaining lithium aluminum hydride; Reaction finishes after product and uses dichloromethane extraction, and organic layer gets 0.36g white solid product k through Hydrogen chloride washing, anhydrous sodium sulfate drying and concentrating under reduced pressure behind silicagel column (dichloromethane/ethyl acetate/THF=5/2/1) purifying; Yield: 85.7 %, de 99% (chiral OD-RH, acetonitrile: water/40:60,0.5 ml/min.
1HNMR(300MHz,?CDCl
3):?δ6.73-6.60(s,?2H),?3.88(s,?12H),?3.73(m,2H),?3.57(s,?6H),?3.35(m,?2H),?2.69(m,?2H),?2.48-2.04(m,?4H)。
(11) getting 0.3mg (0.669 mmol) product k is dissolved in the 5 ml anhydrous pyridines; Add 1.01g under the condition of ice bath; (5.35 mmol) Tosyl chloride reaction 13h, reaction changes in the water after finishing, with twice of ethyl acetate extraction (2 * 15 ml); Organic layer is used anhydrous sodium sulfate drying, obtains compound l behind the concentrating under reduced pressure.
(12) in 6 ml methyl-sulphoxides, add stirring at room reaction 1h behind 0.22g Peng Qinghuana and the above-mentioned products therefrom l; Be warming up to 50 ℃ of reaction 5h then; Being cooled to the room temperature after product changes in the mixture of ice and water; Use anhydrous sodium sulfate drying with ethyl acetate extraction twice (2 * 15 ml), organic layer, remove solvent under reduced pressure, (sherwood oil: ETHYLE ACETATE/3:1) chromatography purification obtains 105 mg title products (P)-couplet benzene ring octadiene compound m to silicagel column; De 99.2%, (chiral OD-RH, acetonitrile: water/90:10,0.5 ml/min), [a]
D 20-74.1 ° of (c1.0, CH
2Cl
2).
1HNMR(300MHz,CDCl
3):?δ6.56(d,?2H),?3.88(m,12H),3.63(s,?4H),?3.58(s,?2H),?2.54-2.12(m,?2H),?1.24(m,?2H),?1.03(m,?3H)，0.83(d,?2H)。
Need to prove at last: a is replaced by 4,5,6 when raw material, 4 '-tetramethoxy-5 ', and 6 '-methylene-dioxy biphenyl-2,2 '-dioctyl phthalate (is R
1=R
2=Me, R
3+ R
4=CH
2), or 4,5,4 ', 5 '-two methylene-dioxies 6,6 '-dimethoxy-2,2 '-biphenyl dicarboxylic acid (is R
1+ R
2=R
3+ R
4=CH
2) time, those skilled in the art can prepare corresponding ultimate aim product (chirality of title product depends on the chiral amino alcohol of being selected for use in the step (2)) with reference to the compound method of embodiment 1, so locate to repeat no more.Above embodiment only is illustrative rather than definitive thereof technical scheme of the present invention; Any modification that the present invention is carried out perhaps is equal to replacement; And any modification or the local replacement that do not break away from spirit and scope of the invention, it all should be encompassed in the middle of the claim scope of the present invention.
Claims (2)
1. the preparation method of a chirality couplet benzene ring octadiene Lignanoids compounds is characterized in that, comprises the steps:
(1) with the compound a be raw material, methylene dichloride or trichloromethane are solvent, and under the thionyl chloride effect, reflux 5-10h obtains product b after steaming desolventizes, and wherein the mol ratio of thionyl chloride and compound a is 2-15:1; R in the structural formula of compound a
1=R
2=R
3=R
4=Me or R
1=R
2=Me, R
3+ R
4=CH
2Or R
1+ R
2=R
3+ R
4=CH
2
(2) product b is dissolved in the methylene dichloride, under condition of ice bath, it is joined then and contain triethylamine and chiral amino alcohol
In the dichloromethane solution, add back room temperature reaction 2-15h, reaction product changes in the water, through extraction, washing, dry and concentrate product c; Wherein the mol ratio of triethylamine and product b is 2-5:1, and the mol ratio of chiral amino alcohol and product b is 2-4:1;
(3) product c is dissolved in the methylene dichloride; Add triethylamine and 4-Dimethylamino pyridine; Under condition of ice bath, add the dichloromethane solution that is dissolved with Tosyl chloride then, add back room temperature reaction 10-30h, reaction product is through washing, the dry and concentrated and purified product d that gets; Wherein the mol ratio of triethylamine and product c is 2-5:1, and the mol ratio of 4-Dimethylamino pyridine and product c is 0.01-0.05:1, and the mol ratio of Tosyl chloride and product c is 2-4:1;
(4) product d is dissolved among the DMF, the cuprous iodide of mol ratios such as adding and product d, under the protection of inert gas, reflux 50-65h steams then and removes DMF, is cooled to room temperature and uses dichloromethane extraction, and extraction liquid is through washing, drying and the concentrated and purified product e that gets;
(5) product e is dissolved in THF, adds SODIUM SULPHATE ANHYDROUS 99PCT, water and trifluoroacetic acid, room temperature reaction 2-10h, reaction product is through dry, the concentrated product f that obtains; Wherein the mol ratio of SODIUM SULPHATE ANHYDROUS 99PCT and water and product e is 10-50:1, and the mol ratio of trifluoroacetic acid and product e is 2-4:1;
(6) product f is dissolved in the methylene dichloride, adds room temperature reaction 15-25h behind aceticanhydride and the pyridine, add methyl alcohol or ethanol synthesis 0.5-10h then, reaction product is through washing, dry and concentrated product g; Wherein the mol ratio of aceticanhydride and product f is 2-20:1, and the mol ratio of pyridine and product f is 5-40:1, and methyl alcohol or ethanol and aceticanhydride mol ratio are 1-4:1;
(7) product g is dissolved among the THF, adds lithium aluminum hydride and react 5-8h in-10-0 ℃, add the excessive acetic acid ethyl ester then remaining lithium aluminum hydride is reacted completely, reaction product with dichloromethane extraction after, through washing, dry and concentrated and purified after must product h; Wherein the mol ratio of lithium aluminum hydride and product g is 1-10:1;
(8) product h is dissolved in the methylene dichloride, adds phosphorus tribromide under the condition of ice bath and react 1h, room temperature continues reaction 5-10h then, and reaction product is isolated organic layer, through washing, dry and concentrate product i; Wherein the mol ratio of phosphorus tribromide and product h is 1-3:1;
(9) in reaction flask, add THF and diisopropylamine under the protection of inert gas condition; Under condition of ice bath, add n-Butyl Lithium reaction 20-40min then; Then reaction flask is added methyl-succinate or diethyl succinate reaction 1-2h in-100--40 ℃ after placing 1-2h; Add the THF solution reaction 1-3h that is dissolved with product i again, then in room temperature reaction 1-5h, reaction product is through extraction, washing, the dry and concentrated and purified product j that gets; Wherein the mol ratio of diisopropylamine and product i is 2-5:1, and n-Butyl Lithium is identical with the addition of diisopropylamine, the mol ratio 1:1 of methyl-succinate or diethyl succinate and product i;
(10) product j is dissolved in the THF; Add lithium aluminum hydride and react 0.5-10h in-10-0 ℃; Add the excessive acetic acid ethyl ester then remaining lithium aluminum hydride reacted completely, reaction product with dichloromethane extraction after, through washing, dry and concentrated and purified after product k; Wherein the mol ratio of lithium aluminum hydride and product j is 1-10:1;
(11) product k is dissolved in the anhydrous pyridine, adds Tosyl chloride reaction 10-15h under the condition of ice bath, reaction product obtains compound l through washing, extraction, drying with after concentrating; Wherein the mol ratio of Tosyl chloride and product k is 2-10:1;
(12) Peng Qinghuana and product l are dissolved in room temperature reaction 1h in the methyl-sulphoxide; Be warming up to 40-50 ℃ of reaction 5-8h then; Be cooled to room temperature and change in the mixture of ice and water, through ethyl acetate extraction, drying and the concentrated and purified title product chirality couplet benzene ring octadiene Lignanoids compounds m that obtains
1Or m
2Wherein the mol ratio of Peng Qinghuana and product l is 2-10:1; Concrete synthetic route is following:
2. the preparation method of chirality couplet benzene ring octadiene Lignanoids compounds according to claim 1 is characterized in that the chiral amino alcohol described in the step (2) comprises L-aminopropanol, L-valerian ammonia alcohol, R-aminopropanol or R-valerian ammonia alcohol.
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| CN111574450A (en) * | 2020-04-29 | 2020-08-25 | 广东工业大学 | Novel chiral biphenyl quaternary ammonium salt phase transfer catalyst and preparation method and application thereof |
| CN111574450B (en) * | 2020-04-29 | 2021-10-29 | 广东工业大学 | Novel chiral biphenyl quaternary ammonium salt phase transfer catalyst and preparation method and application thereof |
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