CN103102254B - The synthetic method of a kind of Pterostilene - Google Patents
The synthetic method of a kind of Pterostilene Download PDFInfo
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- CN103102254B CN103102254B CN201310047013.XA CN201310047013A CN103102254B CN 103102254 B CN103102254 B CN 103102254B CN 201310047013 A CN201310047013 A CN 201310047013A CN 103102254 B CN103102254 B CN 103102254B
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- 238000010189 synthetic method Methods 0.000 title claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 54
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 claims abstract description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 30
- -1 phenyl aldehyde Chemical class 0.000 claims abstract description 27
- YLFBFPXKTIQSSY-UHFFFAOYSA-N dimethoxy(oxo)phosphanium Chemical compound CO[P+](=O)OC YLFBFPXKTIQSSY-UHFFFAOYSA-N 0.000 claims abstract description 21
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims abstract description 14
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 claims abstract description 9
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 7
- 230000032050 esterification Effects 0.000 claims abstract description 7
- 238000005886 esterification reaction Methods 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 90
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 17
- CCAWDIFJOBKBSE-UHFFFAOYSA-N 1-(chloromethyl)-3,5-dimethoxybenzene Chemical compound COC1=CC(CCl)=CC(OC)=C1 CCAWDIFJOBKBSE-UHFFFAOYSA-N 0.000 claims description 14
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 14
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 238000006052 Horner reaction Methods 0.000 claims description 7
- 238000006555 catalytic reaction Methods 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 11
- 238000011084 recovery Methods 0.000 abstract description 9
- 238000003786 synthesis reaction Methods 0.000 abstract description 9
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000006642 detritylation reaction Methods 0.000 abstract description 2
- 239000002699 waste material Substances 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 49
- 238000004128 high performance liquid chromatography Methods 0.000 description 28
- 239000003960 organic solvent Substances 0.000 description 16
- 239000013558 reference substance Substances 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000006073 displacement reaction Methods 0.000 description 9
- 238000010792 warming Methods 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- 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 7
- 239000000463 material Substances 0.000 description 7
- 235000018991 trans-resveratrol Nutrition 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 101150003171 ROMT gene Proteins 0.000 description 5
- 241000219095 Vitis Species 0.000 description 5
- 235000009754 Vitis X bourquina Nutrition 0.000 description 5
- 235000012333 Vitis X labruscana Nutrition 0.000 description 5
- 235000014787 Vitis vinifera Nutrition 0.000 description 5
- VFZRZRDOXPRTSC-UHFFFAOYSA-N 3,5-Dimethoxybenzaldehyde Chemical compound COC1=CC(OC)=CC(C=O)=C1 VFZRZRDOXPRTSC-UHFFFAOYSA-N 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 238000004454 trace mineral analysis Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 244000061176 Nicotiana tabacum Species 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- CSCPPACGZOOCGX-WFGJKAKNSA-N deuterated acetone Substances [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 238000004886 process control Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000003944 tolyl group Chemical group 0.000 description 3
- ZPTVNYMJQHSSEA-UHFFFAOYSA-N 4-nitrotoluene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1 ZPTVNYMJQHSSEA-UHFFFAOYSA-N 0.000 description 2
- 240000001606 Adenanthera pavonina Species 0.000 description 2
- 235000011470 Adenanthera pavonina Nutrition 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 101001106417 Vitis vinifera Trans-resveratrol di-O-methyltransferase Proteins 0.000 description 2
- 230000001857 anti-mycotic effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 150000001989 diazonium salts Chemical class 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- BVJSUAQZOZWCKN-UHFFFAOYSA-N p-hydroxybenzyl alcohol Chemical compound OCC1=CC=C(O)C=C1 BVJSUAQZOZWCKN-UHFFFAOYSA-N 0.000 description 2
- VLEUZFDZJKSGMX-ONEGZZNKSA-N pterostilbene Chemical compound COC1=CC(OC)=CC(\C=C\C=2C=CC(O)=CC=2)=C1 VLEUZFDZJKSGMX-ONEGZZNKSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- HZCDANOFLILNSA-UHFFFAOYSA-N Dimethyl hydrogen phosphite Chemical class COP(=O)OC HZCDANOFLILNSA-UHFFFAOYSA-N 0.000 description 1
- 241000292342 Dracaena cochinchinensis Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 235000017190 Vitis vinifera subsp sylvestris Nutrition 0.000 description 1
- 244000237969 Vitis vulpina Species 0.000 description 1
- 235000017242 Vitis vulpina Nutrition 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003570 biosynthesizing effect Effects 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- VLEUZFDZJKSGMX-UHFFFAOYSA-N pterostilbene Natural products COC1=CC(OC)=CC(C=CC=2C=CC(O)=CC=2)=C1 VLEUZFDZJKSGMX-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
- C09B23/14—Styryl dyes
- C09B23/148—Stilbene dyes containing the moiety -C6H5-CH=CH-C6H5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
- C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses the synthetic method of a kind of Pterostilene, take p-Hydroxybenzaldehyde as raw material, by reacting with triphenylmethyl chloride, obtain trityloxy phenyl aldehyde, again with 3, 5-3,5-dimethoxybenzoic alcohol is raw material, by triphosgene chlorination, gained muriate is again with trimethyl phosphite esterification, obtain 3, 5-dimethoxy benezene dimethyl phosphonate, will to trityloxy phenyl aldehyde and 3, 5-dimethoxy benezene dimethyl phosphonate is obtained by reacting Pterostilene intermediate by Witting-Horner, by this Pterostilene intermediate in acid condition detritylation namely obtain Pterostilene.The present invention is that the synthesis of Pterostilene provides a kind of new synthetic route, and the method raw material is cheap and easy to get, and yield is high, and reaction conditions is gentle, and the three wastes are few, and the solvent used all can recovery, and the rate of recovery is high, is very applicable to industrialized production.
Description
Technical field
The invention belongs to pharmaceutical synthesis field, be specifically related to the synthetic method of a kind of Pterostilene.
Background technology
Pterostilene, chemical name: (E)-3,5-dimethoxy-4 ' '-hydroxy stibene, have another name called: Pterostilene, English name: Pterostilbene, No. CAS: 537-42-8, molecular formula: C
16h
16o
3, molecular weight: 256.30, chemical structural formula is as follows:
Pterostilene is a kind of chemical composition contained in red sandalwood, but scientist has also in succession found the existence of Pterostilene in other plant, but because its Late Cambrian is in red sandalwood, Gu called after Pterostilene.Pterostilene is white or off-white powder crystallization, and have abundant pharmaceutical use, belong to the Active antifungal compound in blood product, the treatment for cancer, hypertension, hyperlipidemia has certain effect.Pterostilene belongs to polyhydroxystilbene compounds, is the homologue of trans-resveratrol, its pharmacological action except to trans-resveratrol have part similar except, also have stronger anti-mycotic activity, its anti-mycotic activity is five times of trans-resveratrol.
At present, the acquisition of Pterostilene has three kinds of modes, and one is plant extract, and a kind of is biosynthesizing, and a kind of is chemosynthesis.
Lu Wenjie etc. (Acta Pharmaceutica Sinica 33:755-758,1998) report and extract Pterostilene from Dracaena cochinchinensis timber.
Chinese patent application CN201010582548.3(publication number CN102120996A) report the biological synthesis process of a kind of Pterostilene, namely grape resveratrol-chlB5 catalysis trans-resveratrol is adopted to prepare Pterostilene, be specially: according to the Chinese wild grape East China grape ROMT gene est sequence obtained, utilize 5 ' and 3 ' RACE full-length gene clone technology clone grape ROMT gene, this gene open reading frame total length is 1074bp; Grape STS and ROMT of clone can proceed in model plant tobacco simultaneously, tobacco plant is utilized to analyze the biosynthetic pathway of grape ROMT catalysis trans-resveratrol generation Pterostilene, for orientation obtains a grape ROMT gene order, this ROMT gene can generate Pterostilene by catalysis trans-resveratrol in transgene tobacco, provides ROMT gene order and method for utilizing phytosynthesis Pterostilene; The method is raw material with trans-resveratrol, and production cost is high.
Chinese patent application CN200310111885.4(publication number CN1539805A) report the chemical synthesis process of a kind of Pterostilene, namely adopt para-nitrotoluene and 3,5-dimethoxy benzaldehyde to be raw material, through condensation, reduction, diazotization, is hydrolyzed and obtains product; Specifically comprise the steps: obtained 3, the 5-dimethoxy-4 ' of 3,5-dimethoxy benzaldehyde, para-nitrotoluene and sodium methylate reaction '-nitro diphenyl ethylene; 3 are obtained by reacting again with hydrazine hydrate, gac and Lewis acid, 5-dimethoxy-4 '-amino-stilbene, then be dissolved in appropriate organic solvent, add sulfuric acid, stir, the sodium nitrite solution that mass concentration is 10% ~ 30% is slowly dripped, the diazonium salt of obtained 3,5-dimethoxy-toluylene under cryosel bath condition; The diazonium salt hydrolysis of 3,5-dimethoxy-toluylene obtains target compound.The yield of the method target product is lower, and cost is high, and products obtained therefrom is second-rate, is not suitable for industrialization.
Chinese patent application CN200510118277.5(publication number CN1955153A) disclose the synthetic method of a kind of Pterostilene; the method is with 3; 5-dimethoxy-benzyl chloride and p-Hydroxybenzaldehyde or with 3; 5-dimethoxy benzaldehyde and p-Hydroxybenzylalcohol (after first protecting chloro); through adopting protection 4 '-hydroxyl and the way making phosphonate reagent; carry out Wei Tixi-Huo Naer (WITTIG-HORNER) reaction, then obtain Pterostilene through hydrolysis or cracking.The yield of the method target product is very low, is not suitable for industrialization.
Summary of the invention
The object of this invention is to provide the synthetic method of a kind of Pterostilene, the synthesis for Pterostilene provides a kind of new synthetic route.
The present invention take p-Hydroxybenzaldehyde as raw material, by reacting with triphenylmethyl chloride, obtain trityloxy phenyl aldehyde, again with 3,5-3,5-dimethoxybenzoic alcohol is raw material, by triphosgene chlorination, gained muriate is again with trimethyl phosphite esterification, obtain 3,5-dimethoxy benezene dimethyl phosphonate, Pterostilene intermediate will be obtained by reacting to trityloxy phenyl aldehyde and 3,5-dimethoxy benezene dimethyl phosphonate by Witting-Horner, by this Pterostilene intermediate in acid condition detritylation namely obtain Pterostilene.Synthetic route of the present invention as shown in Figure 1.
The synthetic method of Pterostilene provided by the invention is specific as follows:
A synthetic method for Pterostilene, comprises the steps:
Step (1): the triphenylmethyl chloride shown in the p-Hydroxybenzaldehyde shown in formula I and formula II is reacted, obtain shown in formula III to trityloxy phenyl aldehyde;
Step (2): by 3 shown in formula IV, 5-3,5-dimethoxybenzoic alcohol and triphosgene carry out chlorination reaction, obtain 3 shown in formula V, 5-dimethoxy benzyl chlorine, again by 3,5-dimethoxy benzyl chlorine and trimethyl phosphite carry out esterification, obtain 3,5-dimethoxy benezene dimethyl phosphonates shown in formula VI;
Step (3): the Pterostilene intermediate shown in formula VII will be obtained by reacting to trityloxy phenyl aldehyde and 3,5-dimethoxy benezene dimethyl phosphonate by Witting-Horner;
Step (4): the Pterostilene intermediate shown in formula VII is carried out trityl removal reaction in acid condition, obtains Pterostilene.
Adopt said synthesis route of the present invention, successfully can prepare Pterostilene, the synthesis for Pterostilene provides a kind of new synthetic route.
Formula I formula II formula III formula IV formula V
Formula VI formula VII
The present invention respectively walks restriction not strict to the consumption between each raw material in reaction, generally presses chemical reaction equation metering ratio and mol ratio 1:1 or part material excessive.Consider from industrial point of view such as the yields that economizes in raw materials, improves, preferably:
In step (1), the mol ratio of p-Hydroxybenzaldehyde and triphenylmethyl chloride is 1:1 ~ 2, more preferably 1:1 ~ 1.2.
In step (2), the mol ratio of 3,5-3,5-dimethoxybenzoic alcohol and triphosgene is 1:0.34 ~ 3, more preferably 1:0.35 ~ 0.5, most preferably is 1:0.4 ~ 0.5; The mol ratio of trimethyl phosphite and 3,5-3,5-dimethoxybenzoic alcohol is 1 ~ 3:1, more preferably 1.05 ~ 1.5:1, most preferably is 1.3 ~ 1.5:1.
In step (3), to mol ratio 1:1 ~ 2 of trityloxy phenyl aldehyde and 3,5-dimethoxy benezene dimethyl phosphonate, more preferably 1:1.3 ~ 1.5.
In order to improve reaction yield further, preferably:
In step (1), described reaction is carried out under triethylamine catalysis.Described triethylamine and the mol ratio of p-Hydroxybenzaldehyde are preferably 1 ~ 3:1, more preferably 1.5 ~ 2:1.
In step (1), described reaction is preferably carried out in organic solvent, and described organic solvent is preferably toluene.Described reaction adds water washing upon reaction completion, and organic solvent layer is through concentration and recovery organic solvent, and the organic solvent of recovery can be reused, and refines, can remove impurity after concentrated with ethanol.
In step (1), the temperature of described reaction is preferably 50 DEG C ~ 70 DEG C, more preferably 55 DEG C ~ 60 DEG C.The time of described reaction strict restriction, by timing sampling, adopting prior art such as high performance liquid chromatography (HPLC) to carry out trace analysis, as reacted complete when p-Hydroxybenzaldehyde, being considered as the terminal reacted.Through overtesting, in order to make reaction carry out completely, generally 50 DEG C ~ 70 DEG C reactions 4 ~ 10 hours, more preferably 55 DEG C ~ 60 DEG C reactions 6 ~ 8 hours.
In step (2), described chlorination reaction is preferably carried out under DMF (DMF) and organic solvent exist, and described organic solvent is preferably toluene.Described triphosgene preferably adopts the mode of dropping to add.Preferred step specifically comprises: by 3,5-3,5-dimethoxybenzoic alcohol is dissolved in toluene, add N, dinethylformamide, drips the toluene solution of triphosgene, continues to react completely after dripping below 15 DEG C, reaction solution separates toluene phase after leaving standstill, through washing and reclaim under reduced pressure toluene, obtain 3,5-dimethoxy benzyl chlorine.3,5-described 3,5-dimethoxybenzoic alcohols and the mol ratio of DMF are preferably 1:0.1 ~ 3, and more preferably 1:0.5 ~ 2, most preferably are 1:0.5 ~ 1.Temperature when dripping triphosgene is preferably 0 DEG C ~ 5 DEG C, drips rear reaction and generally continues reaction 4 ~ 5 hours.
In step (2), the reaction conditions of described esterification is back flow reaction; The time of described esterification strict restriction, by timing sampling, adopting prior art such as high performance liquid chromatography (HPLC) to carry out trace analysis, as reacted complete when 3,5-dimethoxy benzyl chlorine, being considered as the terminal reacted.
In step (3), described Witting-Horner reaction is carried out under sodium methoxide catalyzed.Described sodium methylate with 1 ~ 3:1 is preferably to the mol ratio of trityloxy phenyl aldehyde, more preferably 1.5 ~ 2:1.
In step (3), described Witting-Horner reaction is preferably carried out in organic solvent, and described organic solvent is preferably toluene.Described Witting-Horner reaction, upon reaction completion through simple cooling, is filtered, can be obtained Pterostilene intermediate, reuse after organic solvent is recyclable.
In step (3), the temperature of described Witting-Horner reaction is preferably 50 DEG C ~ 65 DEG C, more preferably 55 DEG C ~ 60 DEG C.The time of described Witting-Horner reaction not strict restriction, pass through timing sampling, adopt prior art such as high performance liquid chromatography (HPLC) to carry out trace analysis, as when complete to the reaction of trityloxy phenyl aldehyde, be considered as the terminal reacted.Through overtesting, in order to make reaction carry out completely, generally 50 DEG C ~ 65 DEG C reactions 8 ~ 16 hours, more preferably 55 DEG C ~ 60 DEG C reactions 10 ~ 12 hours.
In step (4), described acidic conditions is provided by acetic acid, and the mass ratio of the Pterostilene intermediate shown in further preferred formula VII and acetic acid is 1:1 ~ 3, most preferably is 1:1.5 ~ 2.
In step (4), the temperature of described trityl removal reaction is preferably 30 DEG C ~ 45 DEG C, more preferably 40 DEG C ~ 45 DEG C.The time of described trityl removal reaction not strict restriction, pass through timing sampling, prior art such as high performance liquid chromatography (HPLC) is adopted to carry out trace analysis, as complete in the Pterostilene intermediate reaction shown in when formula VII, be considered as the terminal reacted.Through overtesting, in order to make reaction carry out completely, generally react 6 ~ 12 hours at 30 DEG C ~ 45 DEG C, more preferably 40 DEG C ~ 45 DEG C reactions 8 ~ 10 hours.
In step (4), described trityl removal reaction preferably carries out in organic solvent, and described organic solvent is preferably methylene dichloride.Described trityl removal reaction is upon reaction completion through simple cooling, and water and sodium bicarbonate aqueous solution washing, concentrated organic solvent, refines through hexanaphthene, filters, dry, can obtain Pterostilene, reuse after organic solvent is recyclable.
Organic solvent described in the present invention provides solvent environment for reacting.
Raw material of the present invention all can adopt commercially available prod.
The present invention has following beneficial effect:
Synthetic method of the present invention, the synthesis for Pterostilene provides a kind of new synthetic route.
Synthetic method raw material of the present invention is cheap and easy to get, and yield is high, and reaction conditions is gentle, and the three wastes are few, and the solvent used all can recovery, and the rate of recovery is high, is very applicable to industrialized production.
Accompanying drawing explanation
Fig. 1 is synthetic route chart of the present invention.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail.
Embodiment 1
Step (1): add 200ml toluene in reaction flask, then p-Hydroxybenzaldehyde 20g (0.1638mol) is added respectively, triphenylmethyl chloride 50g (0.1794mol), triethylamine 25g (0.2471mol), after adding, be warming up to 57.5 DEG C ± 2.5 DEG C, react 6 hours, be down to room temperature, with 50ml water washing twice, toluene layer is concentrated dry, then adds 80ml ethanol and refine, dry product 54g to trityloxy phenyl aldehyde, molar yield 90.5%(is in p-Hydroxybenzaldehyde).
This product is through contrasting with to trityloxy phenyl aldehyde reference substance, and HPLC goes out peak position, and TLC speckle displacement is all consistent, shows that this product is to trityloxy phenyl aldehyde.
TLC condition: sherwood oil: chloroform: ethyl acetate=1:1:0.1, volume ratio;
HPLC condition is:
Instrument: high performance liquid chromatograph; UV-detector;
Chromatographic column: C
18;
Moving phase: acetonitrile: water=70:30, volume ratio;
Flow velocity: 1.0mL/min;
Column temperature: room temperature;
Sample size: 20 μ l;
Determined wavelength: 250nm.
Step (2): add 41.5g3,5-3,5-dimethoxybenzoic alcohol (0.2467mol), 100ml toluene and 18gDMF(0.2467mol toward reaction flask), be cooled to 5 DEG C; 29.3g(0.0987mol) triphosgene drips after being dissolved in 80ml toluene, drips process control temp 2.5 DEG C ± 2.5 DEG C, drips rear continuation reaction 4 hours; Leave standstill, separate the oil phase that lower floor's color is darker, upper toluene uses a small amount of frozen water and saturated sodium bicarbonate (each 20 milliliters) to wash successively mutually, reconcentration reclaims toluene and obtains product 43.7g3,5-dimethoxy benzyl chlorine, molar yield 95%(is with 3,5-3,5-dimethoxybenzoic alcohol meter).
This product is through contrasting with 3,5-dimethoxy benzyl chlorine reference substance, and HPLC goes out peak position, and TLC speckle displacement is all consistent, shows that this product is 3,5-dimethoxy benzyl chlorine.
TLC condition: sherwood oil: chloroform: ethyl acetate=1:1:0.1, volume ratio;
HPLC condition is:
Instrument: high performance liquid chromatograph; UV-detector;
Chromatographic column: C
18;
Moving phase: acetonitrile: water=80:20, volume ratio;
Flow velocity: 1.0mL/min;
Column temperature: room temperature;
Sample size: 20 μ l;
Determined wavelength: 303nm;
By products therefrom 3,5-dimethoxy benzyl chlorine 43.7g adds 39.8g(0.3207mol) backflow 10 hours in trimethyl phosphite, until oil bath temperature 160 DEG C ± 5 DEG C, interior temperature 150 DEG C, TLC detection reaction terminates, and obtains product 3,5-dimethoxy benezene dimethyl phosphonate 57.8g, molar yield 90%(is with 3,5-3,5-dimethoxybenzoic alcohol meter).
This product is through contrasting with 3,5-dimethoxy benezene dimethyl phosphonate reference substance, and TLC speckle displacement is consistent, shows that this product is 3,5-dimethoxy benezene dimethyl phosphonate.
TLC condition: sherwood oil: chloroform: ethyl acetate=1:1:0.1, volume ratio.
Step (3): by 54g(0.1482mol) to trityloxy phenyl aldehyde, 3,5-dimethoxy benezene dimethyl phosphonate 57.8g (0.2221mol), sodium methylate 16g (0.2962mol) joins in 200ml toluene, is warming up to 57.5 DEG C ± 2.5 DEG C, react 12 hours, be down to room temperature, filter, dry, Pterostilene intermediate 61.3g, molar yield 85%(in trityloxy phenyl aldehyde).
This product is through contrasting with Pterostilene intermediate reference substance, and it is consistent that HPLC goes out peak position, shows that this product is Pterostilene intermediate.
HPLC condition is:
Instrument: high performance liquid chromatograph; UV-detector;
Chromatographic column: C
18;
Moving phase: acetonitrile: water=80:20, volume ratio;
Flow velocity: 1.0mL/min;
Column temperature: room temperature;
Sample size: 20 μ l;
Determined wavelength: 303nm.
Step (4): by Pterostilene intermediate 61.3g(0.126mol) join in 200ml methylene dichloride and dissolve, then add 92g(1.532mol) acetic acid, after adding, be warming up to 42.5 DEG C ± 2.5 DEG C, react 8 hours, be down to room temperature, washing, sodium bicarbonate aqueous solution washs, concentrated methylene dichloride to dry, then add 200ml hexanaphthene and refines, and filters, dry the finished product Pterostilene 29g, molar yield 90%(is with Pterostilene intermediate); Mole total recovery 69.1%(is in p-Hydroxybenzaldehyde).
Pterostilene structural identification data are as follows:
These the finished product are through contrasting with Pterostilene reference substance, and it is consistent that HPLC goes out peak position, tentatively can judge that this material is Pterostilene.
HPLC condition is:
Instrument: high performance liquid chromatograph; UV-detector;
Chromatographic column: C
18;
Moving phase: acetonitrile: water=80:20, volume ratio;
Flow velocity: 1.0mL/min;
Column temperature: room temperature;
Sample size: 20 μ l;
Determined wavelength: 303nm;
LC-MS:m/e255 (M
+-1) show that the molecular weight of this finished product material is 256.3, consistent with the molecular weight of Pterostilene.
Ultimate analysis: C75.06%, H6.35%, consistent with the carbohydrate content of Pterostilene.
Nuclear magnetic data (hydrogen spectrum): solvent deuterated acetone, 300MHz: δ 3.80 (s, 6H), 6.39 (t, J=2.1Hz, 1H), 6.74 (d, J=2.4Hz, 2H), 6.86-6.89 (m, 2H), 6.99 (d, J=16.5Hz, 1H), 7.19 (d, J=16.5Hz, 1H), 7.44-7.47 (m, 2H) 8.60 (brs, 1H-OH).The structural formula that nuclear magnetic data reacts is consistent with Pterostilene.
In sum, gained the finished product are Pterostilene.
Embodiment 2
Step (1): add 200ml toluene in reaction flask, then p-Hydroxybenzaldehyde 20g (0.1638mol) is added respectively, triphenylmethyl chloride 54.8g (0.1966mol), triethylamine 33.2g (0.3276mol), after adding, be warming up to 57.5 DEG C ± 2.5 DEG C, react 8 hours, be down to room temperature, with 50ml water washing twice, toluene layer is concentrated dry, then adds 80ml ethanol and refine, dry product 54.5g to trityloxy phenyl aldehyde, molar yield 91.3%(is in p-Hydroxybenzaldehyde).
This product is through contrasting with to trityloxy phenyl aldehyde reference substance, and HPLC goes out peak position, and TLC speckle displacement is all consistent, shows that this product is to trityloxy phenyl aldehyde.
TLC condition: with embodiment 1;
HPLC condition: with embodiment 1.
Step (2): add 35.8g3,5-3,5-dimethoxybenzoic alcohol (0.2127mol), 100ml toluene and 7.8gDMF(0.1064mol toward reaction flask), be cooled to 5 DEG C; 31.6g(0.1064mol) triphosgene drips after being dissolved in 80ml toluene, drips process control temp 2.5 DEG C ± 2.5 DEG C, drips rear continuation reaction 5 hours; Leave standstill, separate the oil phase that lower floor's color is darker, upper toluene uses a small amount of frozen water and saturated sodium bicarbonate (each 20 milliliters) to wash successively mutually, reconcentration reclaims toluene and obtains product 38.5g3,5-dimethoxy benzyl chlorine, molar yield 96.9%(is with 3,5-3,5-dimethoxybenzoic alcohol meter).
This product is through contrasting with 3,5-dimethoxy benzyl chlorine reference substance, and HPLC goes out peak position, and TLC speckle displacement is all consistent, shows that this product is 3,5-dimethoxy benzyl chlorine.This TLC condition: with embodiment 1; HPLC condition: with embodiment 1.
By products therefrom 3,5-dimethoxy benzyl chlorine 38.5g adds 39.6g(0.319mol) backflow 10.5 hours in trimethyl phosphite, until oil bath temperature 160 DEG C ± 5 DEG C, interior temperature 150 DEG C, TLC detection reaction terminates, and obtains product 3,5-dimethoxy benezene dimethyl phosphonate 50.6g, molar yield 91.4%(is with 3,5-3,5-dimethoxybenzoic alcohol meter).
This product is through contrasting with 3,5-dimethoxy benezene dimethyl phosphonate reference substance, and TLC speckle displacement is consistent, shows that this product is 3,5-dimethoxy benezene dimethyl phosphonate.TLC condition: with embodiment 1.
Step (3): by 54.5g(0.1495mol) to trityloxy phenyl aldehyde, 3,5-dimethoxy benezene dimethyl phosphonate 50.6g (0.1944mol), sodium methylate 16.2g (0.299mol) joins in 200ml toluene, is warming up to 57.5 DEG C ± 2.5 DEG C, react 10 hours, be down to room temperature, filter, dry, Pterostilene intermediate 62.7g, molar yield 86.2%(in trityloxy phenyl aldehyde).
This product is through contrasting with Pterostilene intermediate reference substance, and it is consistent that HPLC goes out peak position, shows that this product is Pterostilene intermediate.HPLC condition is: with embodiment 1.
Step (4): by Pterostilene intermediate 62.7g(0.1288mol) join in 200ml methylene dichloride and dissolve, then add 125.4g(2.088mol) acetic acid, after adding, be warming up to 42.5 DEG C ± 2.5 DEG C, react 10 hours, be down to room temperature, washing, sodium bicarbonate aqueous solution washs, concentrated methylene dichloride to dry, then add 200ml hexanaphthene and refines, and filters, dry the finished product Pterostilene 30g, molar yield 90.9%(is with Pterostilene intermediate); Mole total recovery 71.5%(is in p-Hydroxybenzaldehyde).
Pterostilene structural identification data are as follows:
These the finished product are through contrasting with Pterostilene reference substance, and it is consistent that HPLC goes out peak position, tentatively can judge that this material is Pterostilene.HPLC condition: with embodiment 1.
LC-MS:m/e255 (M
+-1) show that the molecular weight of this finished product material is 256.3, consistent with the molecular weight of Pterostilene.
Ultimate analysis: C75.06%, H6.35%, consistent with the carbohydrate content of Pterostilene.
Nuclear magnetic data (hydrogen spectrum): solvent deuterated acetone, 300MHz: δ 3.80 (s, 6H), 6.39 (t, J=2.1Hz, 1H), 6.74 (d, J=2.4Hz, 2H), 6.86-6.89 (m, 2H), 6.99 (d, J=16.5Hz, 1H), 7.19 (d, J=16.5Hz, 1H), 7.44-7.47 (m, 2H) 8.60 (brs, 1H-OH).The structural formula that nuclear magnetic data reacts is consistent with Pterostilene.
In sum, gained the finished product are Pterostilene.
Embodiment 3
Step (1): add 200ml toluene in reaction flask, then p-Hydroxybenzaldehyde 20g (0.1638mol) is added respectively, triphenylmethyl chloride 91.3g (0.3276mol), triethylamine 49.7g (0.4914mol), after adding, be warming up to 50 DEG C, react 10 hours, be down to room temperature, with 50ml water washing twice, toluene layer is concentrated dry, then adds 80ml ethanol and refine, dry product 52.3g to trityloxy phenyl aldehyde, molar yield 87.6%(is in p-Hydroxybenzaldehyde).
This product is through contrasting with to trityloxy phenyl aldehyde reference substance, and HPLC goes out peak position, and TLC speckle displacement is all consistent, shows that this product is to trityloxy phenyl aldehyde.
TLC condition: with embodiment 1;
HPLC condition: with embodiment 1.
Step (2): add 27.7g3,5-3,5-dimethoxybenzoic alcohol (0.1648mol), 100ml toluene and 0.78gDMF(0.01648mol toward reaction flask), be cooled to 10 DEG C; 146.7g(0.4944mol) triphosgene drips after being dissolved in 80ml toluene, drips process control temp 5 DEG C ± 5 DEG C, drips rear continuation reaction 6 hours; Leave standstill, separate the oil phase that lower floor's color is darker, upper toluene uses a small amount of frozen water and saturated sodium bicarbonate (each 20 milliliters) to wash successively mutually, reconcentration reclaims toluene and obtains product 27.7g3,5-dimethoxy benzyl chlorine, molar yield 90%(is with 3,5-3,5-dimethoxybenzoic alcohol meter).
This product is through contrasting with 3,5-dimethoxy benzyl chlorine reference substance, and HPLC goes out peak position, and TLC speckle displacement is all consistent, shows that this product is 3,5-dimethoxy benzyl chlorine.This TLC condition: with embodiment 1; HPLC condition: with embodiment 1.
By products therefrom 3,5-dimethoxy benzyl chlorine 27.7g adds 20.4g(0.1648mol) backflow 11 hours in trimethyl phosphite, until oil bath temperature 160 DEG C ± 5 DEG C, interior temperature 150 DEG C, TLC detection reaction terminates, and obtains product 3,5-dimethoxy benezene dimethyl phosphonate 37.3g, molar yield 87%(is with 3,5-3,5-dimethoxybenzoic alcohol meter).
This product is through contrasting with 3,5-dimethoxy benezene dimethyl phosphonate reference substance, and TLC speckle displacement is consistent, shows that this product is 3,5-dimethoxy benezene dimethyl phosphonate.TLC condition: with embodiment 1.
Step (3): by 52.3g(0.1435mol) to trityloxy phenyl aldehyde, 3,5-dimethoxy benezene dimethyl phosphonate 37.3g(0.1435mol), sodium methylate 7.8g(0.1435mol) join in 200ml toluene, be warming up to 50 DEG C, react 16 hours, be down to room temperature, filter, dry, Pterostilene intermediate 58g, molar yield 83.1%(in trityloxy phenyl aldehyde).
This product is through contrasting with Pterostilene intermediate reference substance, and it is consistent that HPLC goes out peak position, shows that this product is Pterostilene intermediate.HPLC condition is: with embodiment 1.
Step (4): by Pterostilene intermediate 58g(0.1192mol) join in 200ml methylene dichloride and dissolve, then add 174g(2.8976mol) acetic acid, after adding, be warming up to 30 DEG C, react 12 hours, be down to room temperature, washing, sodium bicarbonate aqueous solution washs, concentrated methylene dichloride to dry, then add 200ml hexanaphthene and refines, and filters, dry the finished product Pterostilene 26.9g, molar yield 88%(is with Pterostilene intermediate); Mole total recovery 64.1%(is in p-Hydroxybenzaldehyde).
Pterostilene structural identification data are as follows:
These the finished product are through contrasting with Pterostilene reference substance, and it is consistent that HPLC goes out peak position, tentatively can judge that this material is Pterostilene.HPLC condition: with embodiment 1.
LC-MS:m/e255 (M
+-1) show that the molecular weight of this finished product material is 256.3, consistent with the molecular weight of Pterostilene.
Ultimate analysis: C75.06%, H6.35%, consistent with the carbohydrate content of Pterostilene.
Nuclear magnetic data (hydrogen spectrum): solvent deuterated acetone, 300MHz: δ 3.80 (s, 6H), 6.39 (t, J=2.1Hz, 1H), 6.74 (d, J=2.4Hz, 2H), 6.86-6.89 (m, 2H), 6.99 (d, J=16.5Hz, 1H), 7.19 (d, J=16.5Hz, 1H), 7.44-7.47 (m, 2H) 8.60 (brs, 1H-OH).The structural formula that nuclear magnetic data reacts is consistent with Pterostilene.
In sum, gained the finished product are Pterostilene.
In synthetic method of the present invention, the change of parameter does not affect the synthesis of Pterostilene, and therefore in synthetic method of the present invention, the combination of arbitrary parameter all can realize the preparation of Pterostilene.Do not repeat them here.
Claims (5)
1. a synthetic method for Pterostilene, is characterized in that, comprises step:
Step (1): p-Hydroxybenzaldehyde and triphenylmethyl chloride are reacted, obtains trityloxy phenyl aldehyde;
Described reaction is carried out under triethylamine catalysis in toluene solvant;
The temperature of described reaction is 50 DEG C ~ 70 DEG C;
Step (2): 3,5-3,5-dimethoxybenzoic alcohol and triphosgene are carried out chlorination reaction, obtains 3,5-dimethoxy benzyl chlorine, then 3,5-dimethoxy benzyl chlorine and trimethyl phosphite are carried out esterification, obtain 3,5-dimethoxy benezene dimethyl phosphonate;
Described chlorination reaction is carried out under DMF and toluene solvant exist;
The temperature of described chlorination reaction is below 15 DEG C; The reaction conditions of described esterification is back flow reaction;
Step (3): the Pterostilene intermediate shown in formula VII will be obtained by reacting to trityloxy phenyl aldehyde and 3,5-dimethoxy benezene dimethyl phosphonate by Witting-Horner;
Described Witting-Horner reaction is carried out under sodium methoxide catalyzed in toluene solvant;
The temperature of described Witting-Horner reaction is 50 DEG C ~ 65 DEG C;
Step (4): the Pterostilene intermediate shown in formula VII is carried out trityl removal reaction in acid condition, obtains Pterostilene;
Described trityl removal reaction carries out in dichloromethane solvent;
The temperature of described trityl removal reaction is 30 DEG C ~ 45 DEG C;
2. the synthetic method of Pterostilene according to claim 1, is characterized in that, in step (1), the mol ratio of p-Hydroxybenzaldehyde and triphenylmethyl chloride is 1:1 ~ 2;
In step (2), the mol ratio of 3,5-3,5-dimethoxybenzoic alcohol and triphosgene is 1:0.34 ~ 3; The mol ratio of trimethyl phosphite and 3,5-3,5-dimethoxybenzoic alcohol is 1 ~ 3:1;
In step (3), to mol ratio 1:1 ~ 2 of trityloxy phenyl aldehyde and 3,5-dimethoxy benezene dimethyl phosphonate.
3. the synthetic method of Pterostilene according to claim 1, is characterized in that, in step (2), described triphosgene adopts the mode dripped to add.
4. the synthetic method of Pterostilene according to claim 3, is characterized in that, temperature when dripping triphosgene is 0 DEG C ~ 5 DEG C.
5. the synthetic method of Pterostilene according to claim 1, is characterized in that, in step (4), described acidic conditions is provided by acetic acid, and the mass ratio of the Pterostilene intermediate shown in formula VII and acetic acid is 1:1 ~ 3.
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