CN108675918A - A kind of synthetic method of piceatannol - Google Patents
A kind of synthetic method of piceatannol Download PDFInfo
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- CN108675918A CN108675918A CN201810530492.3A CN201810530492A CN108675918A CN 108675918 A CN108675918 A CN 108675918A CN 201810530492 A CN201810530492 A CN 201810530492A CN 108675918 A CN108675918 A CN 108675918A
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- Prior art keywords
- hydroxyls
- piceatannol
- reaction
- added
- talan
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- IIXHQGSINFQLRR-UHFFFAOYSA-N Piceatannol Natural products Oc1ccc(C=Cc2c(O)c(O)c3CCCCc3c2O)cc1O IIXHQGSINFQLRR-UHFFFAOYSA-N 0.000 title claims abstract description 30
- CDRPUGZCRXZLFL-OWOJBTEDSA-N piceatannol Chemical compound OC1=CC(O)=CC(\C=C\C=2C=C(O)C(O)=CC=2)=C1 CDRPUGZCRXZLFL-OWOJBTEDSA-N 0.000 title claims abstract description 30
- 238000010189 synthetic method Methods 0.000 title claims description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- HDWLUGYOLUHEMN-UHFFFAOYSA-N Dinobuton Chemical compound CCC(C)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1OC(=O)OC(C)C HDWLUGYOLUHEMN-UHFFFAOYSA-N 0.000 claims abstract description 21
- 241000425573 Talanes Species 0.000 claims abstract description 19
- 239000007858 starting material Substances 0.000 claims abstract description 6
- 230000017858 demethylation Effects 0.000 claims abstract description 3
- 238000010520 demethylation reaction Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims description 19
- 238000003786 synthesis reaction Methods 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 14
- 230000015572 biosynthetic process Effects 0.000 claims description 14
- 239000012074 organic phase Substances 0.000 claims description 12
- 230000035484 reaction time Effects 0.000 claims description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 9
- 238000004440 column chromatography Methods 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 9
- FXEIWOUGVRUQNK-UHFFFAOYSA-N 5-ethenyl-2-methoxyphenol Chemical class COC1=CC=C(C=C)C=C1O FXEIWOUGVRUQNK-UHFFFAOYSA-N 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 229910052763 palladium Inorganic materials 0.000 claims description 7
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 claims description 6
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 claims description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- KRWRFIMBWRVMKE-UHFFFAOYSA-N 1-bromo-3,5-dimethoxybenzene Chemical class COC1=CC(Br)=CC(OC)=C1 KRWRFIMBWRVMKE-UHFFFAOYSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 239000002537 cosmetic Substances 0.000 claims description 3
- 230000006837 decompression Effects 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims 2
- HTDQSWDEWGSAMN-UHFFFAOYSA-N 1-bromo-2-methoxybenzene Chemical compound COC1=CC=CC=C1Br HTDQSWDEWGSAMN-UHFFFAOYSA-N 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 150000001299 aldehydes Chemical class 0.000 claims 1
- 238000001816 cooling Methods 0.000 claims 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 claims 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- UAJRSHJHFRVGMG-UHFFFAOYSA-N 1-ethenyl-4-methoxybenzene Chemical compound COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-UHFFFAOYSA-N 0.000 abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 5
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 abstract 2
- UCEJNFOIRGNMKV-UHFFFAOYSA-N 1-bromo-2,3-dimethoxybenzene Chemical class COC1=CC=CC(Br)=C1OC UCEJNFOIRGNMKV-UHFFFAOYSA-N 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 238000007341 Heck reaction Methods 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003859 lipid peroxidation Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 230000001012 protector Effects 0.000 description 2
- 230000033458 reproduction Effects 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 244000050510 Cunninghamia lanceolata Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- 244000288157 Passiflora edulis Species 0.000 description 1
- 235000000370 Passiflora edulis Nutrition 0.000 description 1
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 1
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
- 240000000851 Vaccinium corymbosum Species 0.000 description 1
- 235000003095 Vaccinium corymbosum Nutrition 0.000 description 1
- 235000017537 Vaccinium myrtillus Nutrition 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 235000021014 blueberries Nutrition 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- PMOIAJVKYNVHQE-UHFFFAOYSA-N phosphanium;bromide Chemical compound [PH4+].[Br-] PMOIAJVKYNVHQE-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000021283 resveratrol Nutrition 0.000 description 1
- 229940016667 resveratrol Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 1
- 235000021286 stilbenes Nutrition 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
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- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
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Abstract
The present invention is using 3 hydroxyl, 4 methoxybenzaldehyde as starting material, it is reacted through wittig and generates 3 hydroxyl, 4 methoxy styrene, 3 hydroxyl, 4 methoxy styrene and 3,3 hydroxyls of E, 3 ＇ is obtained by the reaction through Heck in 5 dimethoxy bromobenzenes, 4,5 ＇ trimethoxy talan, 3 hydroxyls of E, 3 ＇, 4,5 ＇ trimethoxies talan obtain target product piceatannol through demethylation again.Structure as talan parent nucleus is reacted using Heck, the target product of single configuration can be obtained, starting material is cheap and easy to get, easy to operate, mild condition, and yield is higher.
Description
Technical field
The invention belongs to synthesize field, more particularly to a kind of synthetic method of piceatannol.
Background technology
Piceatannol is one kind of natural extract stilbene substance, is 3 hydroxylated analogs of resveratrol, grape,
The presence of piceatannol is found in the plants such as blueberry, passion fruit, sugarcane.Pharmaceutical research shows the medicine there are many piceatannols
Reason activity, there is a variety of pharmacological activity such as anticancer, suppressing cell reproduction, anti-inflammatory, immunological regulation lipid peroxidation inhibition, antibacterial.Studies have shown that
Piceatannol or good antioxidant and cardiovascular protector.With deepening continuously for exploitation, piceatannol health products,
The fields such as cosmetics and drug are widely used and approve.
Piceatannol is mainly derived from plant extract at present.This method cost is higher, and yield unfriendly to environment is very low.
Therefore, artificial synthesized research becomes the emphasis of world today's concern.The crucial synthesis of piceatannol is mainly two phenyl ring
Coupling reaction, the i.e. synthesis of talan skeleton.In addition it is contemplated that the problem of cis-trans isomerism.Talan skeleton at present
Structure mainly has Wittig (Wittig) reactions, Wittig-Horner (Wei Dihuona) reactions, Perkin (Poole gold) reaction
Deng.
The chemical synthesis research method of piceatannol is less, mainly with Li Xiaoxia, Yan An, Duan Hanying piceatannols
Synthesis [J]《Fine chemistry industry》5 interim reacted using Wittig-Horne synthesize piceatannol within 2011, and synthetic route is：
Noxious material PBr has been used in synthetic route starting material costliness and building-up process3, meet water and fiercely react generation
Hydrogen bromide and phosphorous acid release irritation steam and cause corrosive burn.Steam and liquid can seriously stimulate eyes, mucous membrane,
Skin and respiratory system cause to burn, and frequent inhalation of low concentration steam can damage respiratory tract.And there is post-processing complexity, yield
The shortcomings of relatively low.Therefore seeking a kind of synthetic method of simplicity becomes the most important thing.
Invention content
In acquisition methods in order to overcome existing piceatannol, there is biology extraction and be difficult to meet the market demand, cost compared with
Height, and yield unfriendly to environment is very low, and chemical synthesis is complicated for operation, and post-processing is difficult, and target product structure is not single to be lacked
Point.
The present invention uses starting material cheap and easy to get, and the structure for completing talan parent nucleus is reacted by Heck, to
Single anti-configuration piceatannol is obtained, there is preferable development prospect.
With 3- hydroxyls -4-methoxybenzaldehyde (2) for starting material, is reacted through wittig (Wittig) and generate 3- hydroxyls -
E-3- hydroxyls -3 ＇, 4,5 ＇-is obtained by the reaction through Heck (He Ke) with 3,5- dimethoxys bromobenzene in 4- methoxy styrenes (3), (3)
Trimethoxy talan (4), (4) obtain target product (1) through demethylation again.
Its synthetic route is as follows：
Specifically synthesis technology step is：
(1) synthesis of 3- hydroxyls -4- methoxy styrenes
3- hydroxyls -4-methoxybenzaldehyde is added in round-bottomed flask, 50mL tetrahydrofurans are added and are dissolved, then again
Potassium tert-butoxide is added, finally adds methyltriphenylphosphonium bromide, is detected through TLC after heating reaction, reaction terminates.It is cooled to room
Temperature is added 50mL water, is extracted with ethyl acetate (50mL × 3), merges organic phase, with saturated common salt water washing (100mL × 3),
It is finally dried with anhydrous sodium sulfate, is spin-dried for obtaining yellow oil, column chromatography (ethyl acetate：Petroleum ether=1:30,1L) purifying obtains
White solid matter 3- hydroxyl -4- methoxy styrenes (3).
Wherein, the molar ratio of 3- hydroxyls -4-methoxybenzaldehyde, potassium tert-butoxide and methyltriphenylphosphonium bromide is：1：
2.0-4.0：2.0-4.0, reaction temperature：60-80 DEG C, the reaction time：5-8h.
(2) synthesis of -3 ＇ of E-3- hydroxyls, 4,5 ＇-trimethoxy talan
3- hydroxyl -4- methoxy styrenes are added in round-bottomed flask, 15mLDMF is added and is dissolved, then adds successively
Enter 3,5- dimethoxy bromobenzenes, wet chemical (1.0g is dissolved in 10mL water), tetrabutylammonium bromide, palladium, triphenyl
Phosphine detects after heating reaction through TLC, and reaction terminates.It is cooled to room temperature, suction filtered through kieselguhr, filtrate is with ethyl acetate (50mL × 3)
Extraction merges organic phase, washs organic phase (200mL × 6) with saturated brine, anhydrous sodium sulfate drying, filtering, filtrate is through 50 DEG C
Evaporated under reduced pressure obtains yellow oil, column chromatography (ethyl acetate：Petroleum ether=1:20,2.5L) purifying obtains white solid powder E-3- hydroxyls
Base -3 ＇, 4,5 ＇-trimethoxy talan.
Wherein, 3- hydroxyls -4- methoxy styrenes, 3,5- dimethoxy bromobenzenes, potassium carbonate, tetrabutylammonium bromide, acetic acid
The molar ratio of palladium and triphenylphosphine is：1:1.1-1.6:1.8-2.4:0.05-0.15:0.03-0.08:0.08-0.15, reaction temperature
Degree is：100-140 DEG C, reaction time 5-10h.
(3) synthesis of piceatannol
First it will be preheated to 100 DEG C in round-bottomed flask, then add pyridine hydrochloride, be heated to 180 DEG C, waits for pyridine hydrochloric acid
After salt dissolving, E-3- hydroxyls -3 ＇, 4,5 ＇-trimethoxy talan is added, then detected through TLC after temperature reaction, reaction knot
Beam.It is cooled to room temperature, 30mL water is added, is extracted with ethyl acetate (50mL × 3), merge organic phase, with saturated common salt water washing
(100mL × 3), are finally dried with anhydrous sodium sulfate, and filtrate is spin-dried for obtaining aterrimus oil, column chromatography (methanol through 50 DEG C of decompressions：Two
Chloromethanes=1:20,1.5L) purifying obtains gray solid piceatannol.
Wherein, the molar ratio of pyridine hydrochloride and E-3- hydroxyls -3 ＇, 4,5 ＇-trimethoxy talan is：50-80：1,
Reaction temperature is：180-260 DEG C, the reaction time is：0.5-1.5h.
There are piceatannol a variety of pharmacology such as anticancer, suppressing cell reproduction, anti-inflammatory, immunological regulation lipid peroxidation inhibition, antibacterial to live
Property.Studies have shown that piceatannol or good antioxidant and cardiovascular protector.The piceatannol that the present invention synthesizes is available
In fields such as health products, cosmetics and drugs.
Advantageous effect
The present invention has higher anti diastereoselectivity, higher yield, and reaction condition temperature using Heck reactions
With, simple operation and other advantages, uses Heck reactions as crucial alkene coupling step for the first time, obtain the white skin of single anti-configuration
China fir alcohol.With preferable development prospect.The preparation method reduces production cost；Improve yield；Obtain single E configuration mesh
Mark product.
Specific implementation mode
Embodiment 1
(1) synthesis of 3- hydroxyls -4- methoxy styrenes
3- hydroxyls -4-methoxybenzaldehyde (2.0g, 13.14mmol) is added in 100mL round-bottomed flasks, is then added
50mL tetrahydrofurans are dissolved, and are then added potassium tert-butoxide (4.4g, 39.21mmol), are finally added methyl triphenyl
Bromide phosphine (12.7g, 35.55mmol) heats 70 DEG C (degree Celsius), is detected through TLC after 7h, reaction terminates.It is cooled to room temperature, adds
Enter 50mL water, be extracted with ethyl acetate (50mL × 3), merges organic phase and finally used with saturated common salt water washing (100mL × 3)
Anhydrous sodium sulfate is dried, and is spin-dried for obtaining yellow oil 2.6g, column chromatography (ethyl acetate：Petroleum ether=1:30,1L) purifying obtains white
Color solid matter 3- hydroxyl -4- methoxy styrene 1.2g, yield 60.91%.1H NMR(300MHz,CDCl3)δ：3.77(s,
3H), 5.08 (d, J=12.0Hz, 1H), 5.66 (d, J=18.0Hz, 1H), 6.68 (dd, J=18.0and12.0Hz, 1H),
6.88(m,3H),9.00(s,1H)。
(2) synthesis of -3 ＇ of E-3- hydroxyls, 4,5 ＇-trimethoxy talan
3- hydroxyl -4- methoxy styrenes (0.5g, 3.33mmol) are added in the round-bottomed flask of 50ml, are added
15mLDMF is dissolved, and 3,5- dimethoxys bromobenzene (1.0g, 4.61mmol), wet chemical are then sequentially added
(1.0g is dissolved in 10mL water), tetrabutylammonium bromide (107.3mg, 0.33mmol), palladium (37.4mg, 0.17mmol), triphen
Base phosphine (104.8mg, 0.40mmol) is heated to 120 DEG C of reactions, is detected through TLC after 8h, reaction terminates.It is cooled to room temperature, diatom
Soil filters, and filtrate is extracted with ethyl acetate (50mL × 3), merges organic phase, organic phase (200mL × 6) is washed with saturated brine,
Anhydrous sodium sulfate is dried, and filtering, filtrate obtains yellow oil 1.6g, column chromatography (ethyl acetate through 50 DEG C of evaporated under reduced pressure：Petroleum ether=1:
20,2.5L) purifying obtains white solid powder 0.6g, yield 63.16%.1H NMR(400MHz,CDCl3)δ：3.78(s,9H),
6.38 (t, 1H), 6.73 (d, 2H), 6.93 (m, 2H), 7.04 (m, 2H), 7.13 (d, J=15.0Hz, 1H), 9.03 (s, 1H).
(3) synthesis of piceatannol
The round-bottomed flask of 50ml is first preheated to 100 DEG C, then adds pyridine hydrochloride (5g, 43.27mmol), is heated
To 180 DEG C, after the dissolving of its pyridine hydrochloride, -3 ＇ of E-3- hydroxyls is added, 4,5 ＇-trimethoxies talan (0.2g,
0.70mmol), 240 DEG C are warming up to then, is detected through TLC after 1h, reaction terminates.It is cooled to room temperature, 30mL water is added, with acetic acid second
Ester extracts (50mL × 3), merges organic phase and is finally dried with anhydrous sodium sulfate with saturated common salt water washing (100mL × 3), is filtered
Liquid is spin-dried for obtaining aterrimus oil 230mg, column chromatography (methanol through 50 DEG C of decompressions：Dichloromethane=1:20,1.5L) purifying obtains ash
Color solid 92mg, yield 53.93%.1H NMR(400MHz,CDCl3)δ：6.10 (t, 1H), 6.36 (d, 2H), 6.68 (d, J=
16.0Hz,1H),6.72(d,1H),6.82(d,1H),6.86(m,1H),6.96(d,1H),8.93(s,1H),9.10(s,1H),
9.19(s,2H)。
Embodiment 2
The molar ratio of 3- hydroxyls -4-methoxybenzaldehyde in step (1), potassium tert-butoxide and methyltriphenylphosphonium bromide is：
1：2.5：2.5, reaction temperature：75 DEG C, the reaction time：6h.
3- hydroxyls -4- methoxy styrenes in step (2), 3,5- dimethoxy bromobenzenes, potassium carbonate, tetrabutylammonium bromide,
Palladium and the molar ratio of triphenylphosphine are：1:1.2:2.0:0.08:0.06:0.08, reaction temperature is：110 DEG C, the reaction time
For 6.5h.
The molar ratio of pyridine hydrochloride and E-3- hydroxyls -3 ＇, 4,5 ＇-trimethoxy talan is in step (3)：60：
1, reaction temperature is：200 DEG C, the reaction time is：1.5h.
Embodiment 3
The molar ratio of 3- hydroxyls -4-methoxybenzaldehyde in step (1), potassium tert-butoxide and methyltriphenylphosphonium bromide is：
1：3.5：3.5, reaction temperature：80 DEG C, the reaction time：8h.
3- hydroxyls -4- methoxy styrenes in step (2), 3,5- dimethoxy bromobenzenes, potassium carbonate, tetrabutylammonium bromide,
Palladium and the molar ratio of triphenylphosphine are：1:1.5:2.2:0.12:0.08:0.1, reaction temperature is：130 DEG C, the reaction time
For 9h.
The molar ratio of pyridine hydrochloride and E-3- hydroxyls -3 ＇, 4,5 ＇-trimethoxy talan is in step (3)：80：
1, reaction temperature is：260 DEG C, the reaction time is：0.5h.
Claims (6)
1. a kind of synthetic method of piceatannol, it is characterised in that：The synthetic method is：With 3- hydroxyl -4- methoxybenzene first
Aldehyde is starting material, is reacted through wittig and generates 3- hydroxyl -4- methoxy styrenes, 3- hydroxyl -4- methoxy styrenes and 3,
E-3- hydroxyls -3 ＇, 4,5 ＇-trimethoxy talan is obtained by the reaction through Heck in 5- dimethoxys bromobenzene, E-3- hydroxyls -3 ＇, and 4,
5 ＇-trimethoxy talan obtains piceatannol through demethylation again.
2. the synthetic method of piceatannol as described in claim 1, it is characterised in that：The synthetic method specific steps are such as
Under：
(1) synthesis of 3- hydroxyls -4- methoxy styrenes
3- hydroxyls -4-methoxybenzaldehyde is added in round-bottomed flask, tetrahydrofuran is added and is dissolved, tertiary fourth is then added
Potassium alcoholate finally adds methyltriphenylphosphonium bromide, is detected through TLC after heating reaction, and reaction terminates, and is cooled to room temperature, and is added
50mL water, is extracted with ethyl acetate, and merges organic phase and is finally dried with anhydrous sodium sulfate with saturated common salt water washing, is spin-dried for
To yellow oil, column chromatography purifies to obtain white solid matter 3- hydroxyl -4- methoxy styrenes；
(2) synthesis of -3 ＇ of E-3- hydroxyls, 4,5 ＇-trimethoxy talan
3- hydroxyl -4- methoxy styrenes are added in round-bottomed flask, DMF is added and is dissolved, 3,5- bis- is then sequentially added
Methoxybromobenzene, wet chemical, tetrabutylammonium bromide, palladium, triphenylphosphine are detected through TLC after heating reaction, are reacted
Terminate, be cooled to room temperature, suction filtered through kieselguhr, filtrate is extracted with ethyl acetate, and merges organic phase, is washed with saturated brine organic
Phase, anhydrous sodium sulfate drying, filtering, filtrate obtain yellow oil through 50 DEG C of evaporated under reduced pressure, and column chromatography purifies to obtain white solid powder
E-3- hydroxyls -3 ＇, 4,5 ＇-trimethoxy talan；
(3) synthesis of piceatannol
Round-bottomed flask is first preheated to 100 DEG C, then adds pyridine hydrochloride, is heated to 180 DEG C, waits for that pyridine hydrochloride dissolves
Afterwards, E-3- hydroxyls -3 ＇, 4,5 ＇-trimethoxy talan is added, is detected through TLC after temperature reaction, reaction terminates, cooling
To room temperature, 30mL water is added, is extracted with ethyl acetate, merges organic phase and finally use anhydrous sodium sulfate with saturated common salt water washing
Dry, filtrate is spin-dried for obtaining aterrimus oil through 50 DEG C of decompressions, and column chromatography purifies to obtain gray solid piceatannol.
3. the synthetic method of piceatannol as described in claim 1, it is characterised in that：Step (1) 3- hydroxyls -4- methoxies
The molar ratio of benzaldehyde, potassium tert-butoxide and methyltriphenylphosphonium bromide is：1：2.0-4.0：2.0-4.0, reaction temperature：60-
80 DEG C, the reaction time：5-8h.
4. the synthetic method of piceatannol as described in claim 1, it is characterised in that：Step (2) 3- hydroxyls -4- methoxies
The molar ratio of base styrene, 3,5- dimethoxy bromobenzenes, potassium carbonate, tetrabutylammonium bromide, palladium and triphenylphosphine is：1:
1.1-1.6:1.8-2.4:0.05-0.15:0.03-0.08:0.08-0.15；Reaction temperature is：100-140 DEG C, the reaction time is
5-10h。
5. the synthetic method of piceatannol as described in claim 1, it is characterised in that：Step (3) pyridine hydrochloride and
The molar ratio of E-3- hydroxyls -3 ＇, 4,5 ＇-trimethoxy talan is：50-80：1, reaction temperature is：180-260 DEG C, reaction
Time is：0.5-1.5h.
6. a kind of application of the piceatannol of method synthesis as described in claim 1, it is characterised in that：The piceatannol is used for
Health products, cosmetics and medicine field.
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| CN103214354A (en) * | 2013-04-28 | 2013-07-24 | 上海大学 | Preparation method of trans-stilbene compound and water-soluble derivative of compound |
| CN105439824A (en) * | 2015-11-06 | 2016-03-30 | 陕西嘉禾生物科技股份有限公司 | Synthesis method of piceatannol |
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| CN103214354A (en) * | 2013-04-28 | 2013-07-24 | 上海大学 | Preparation method of trans-stilbene compound and water-soluble derivative of compound |
| CN105439824A (en) * | 2015-11-06 | 2016-03-30 | 陕西嘉禾生物科技股份有限公司 | Synthesis method of piceatannol |
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