CN103351291B - It is a kind of that natural phlorizin is semi-synthetic prepares Phloretin technique - Google Patents
It is a kind of that natural phlorizin is semi-synthetic prepares Phloretin technique Download PDFInfo
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- VGEREEWJJVICBM-UHFFFAOYSA-N phloretin Chemical compound C1=CC(O)=CC=C1CCC(=O)C1=C(O)C=C(O)C=C1O VGEREEWJJVICBM-UHFFFAOYSA-N 0.000 title claims abstract description 92
- ZWTDXYUDJYDHJR-UHFFFAOYSA-N (E)-1-(2,4-dihydroxyphenyl)-3-(2,4-dihydroxyphenyl)-2-propen-1-one Natural products OC1=CC(O)=CC=C1C=CC(=O)C1=CC=C(O)C=C1O ZWTDXYUDJYDHJR-UHFFFAOYSA-N 0.000 title claims abstract description 46
- YQHMWTPYORBCMF-UHFFFAOYSA-N Naringenin chalcone Natural products C1=CC(O)=CC=C1C=CC(=O)C1=C(O)C=C(O)C=C1O YQHMWTPYORBCMF-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 229940126902 Phlorizin Drugs 0.000 title claims abstract description 34
- IOUVKUPGCMBWBT-UHFFFAOYSA-N phloridzosid Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 235000019139 phlorizin Nutrition 0.000 title claims abstract description 34
- IOUVKUPGCMBWBT-GHRYLNIYSA-N phlorizin Chemical compound O[C@@H]1[C@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-GHRYLNIYSA-N 0.000 title claims abstract description 33
- 238000000034 method Methods 0.000 title claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000012043 crude product Substances 0.000 claims abstract description 10
- 239000002841 Lewis acid Substances 0.000 claims abstract description 7
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 7
- 229910052751 metal Inorganic materials 0.000 claims abstract description 7
- 239000002184 metal Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 238000002425 crystallisation Methods 0.000 claims abstract description 5
- 230000008025 crystallization Effects 0.000 claims abstract description 5
- 239000008367 deionised water Substances 0.000 claims abstract description 5
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 5
- 210000003298 dental enamel Anatomy 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000001035 drying Methods 0.000 claims abstract description 4
- 201000000849 skin cancer Diseases 0.000 claims abstract description 3
- 201000008261 skin carcinoma Diseases 0.000 claims abstract description 3
- 230000002087 whitening effect Effects 0.000 claims abstract description 3
- 239000003513 alkali Substances 0.000 claims abstract 3
- 238000003756 stirring Methods 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000000047 product Substances 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 7
- 239000012266 salt solution Substances 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 238000004809 thin layer chromatography Methods 0.000 claims description 4
- 238000010792 warming Methods 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 claims description 2
- 239000012535 impurity Substances 0.000 claims description 2
- LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical group O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 claims description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- 238000000967 suction filtration Methods 0.000 claims 3
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims 2
- 239000002585 base Substances 0.000 claims 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims 2
- 241000050051 Chelone glabra Species 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 239000001569 carbon dioxide Substances 0.000 claims 1
- 229910002092 carbon dioxide Inorganic materials 0.000 claims 1
- 239000013058 crude material Substances 0.000 claims 1
- 229960003280 cupric chloride Drugs 0.000 claims 1
- 229910052500 inorganic mineral Inorganic materials 0.000 claims 1
- 229910052742 iron Inorganic materials 0.000 claims 1
- 239000011707 mineral Substances 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 239000005051 trimethylchlorosilane Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 238000001914 filtration Methods 0.000 abstract description 4
- 229910001220 stainless steel Inorganic materials 0.000 abstract description 4
- 239000010935 stainless steel Substances 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 3
- 239000012141 concentrate Substances 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000007670 refining Methods 0.000 abstract 1
- 241000220225 Malus Species 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000003292 diminished effect Effects 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 150000008442 polyphenolic compounds Chemical class 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010029098 Neoplasm skin Diseases 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 239000001058 brown pigment Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- -1 phlorizin sodium-salt Chemical class 0.000 description 2
- 238000004886 process control Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 description 1
- HSTZMXCBWJGKHG-UHFFFAOYSA-N (E)-piceid Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=CC(C=CC=2C=CC(O)=CC=2)=C1 HSTZMXCBWJGKHG-UHFFFAOYSA-N 0.000 description 1
- LDCVEPMPZLHMMK-UHFFFAOYSA-N 11h-benzo[a]fluoren-1-ol Chemical compound C1=CC=C2CC3=C4C(O)=CC=CC4=CC=C3C2=C1 LDCVEPMPZLHMMK-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 description 1
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 description 1
- 241000219998 Philenoptera violacea Species 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
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- IVTMALDHFAHOGL-UHFFFAOYSA-N eriodictyol 7-O-rutinoside Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C=C3C(C(C(O)=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 IVTMALDHFAHOGL-UHFFFAOYSA-N 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 description 1
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 description 1
- 229940025878 hesperidin Drugs 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- IQPNAANSBPBGFQ-UHFFFAOYSA-N luteolin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C(O)=C1 IQPNAANSBPBGFQ-UHFFFAOYSA-N 0.000 description 1
- LRDGATPGVJTWLJ-UHFFFAOYSA-N luteolin Natural products OC1=CC(O)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 LRDGATPGVJTWLJ-UHFFFAOYSA-N 0.000 description 1
- 235000009498 luteolin Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960003764 polydatin Drugs 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 1
- ALABRVAAKCSLSC-UHFFFAOYSA-N rutin Natural products CC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5 ALABRVAAKCSLSC-UHFFFAOYSA-N 0.000 description 1
- 235000005493 rutin Nutrition 0.000 description 1
- 229960004555 rutoside Drugs 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- DKVBOUDTNWVDEP-NJCHZNEYSA-N teicoplanin aglycone Chemical compound N([C@H](C(N[C@@H](C1=CC(O)=CC(O)=C1C=1C(O)=CC=C2C=1)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)OC=1C=C3C=C(C=1O)OC1=CC=C(C=C1Cl)C[C@H](C(=O)N1)NC([C@H](N)C=4C=C(O5)C(O)=CC=4)=O)C(=O)[C@@H]2NC(=O)[C@@H]3NC(=O)[C@@H]1C1=CC5=CC(O)=C1 DKVBOUDTNWVDEP-NJCHZNEYSA-N 0.000 description 1
- HSTZMXCBWJGKHG-CUYWLFDKSA-N trans-piceid Polymers O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(\C=C\C=2C=CC(O)=CC=2)=C1 HSTZMXCBWJGKHG-CUYWLFDKSA-N 0.000 description 1
- 235000018991 trans-resveratrol Nutrition 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The semi-synthesizing technology that the present invention is is raw material production whitening and anti-skin carcinoma activeconstituents Phloretin with the phlorizin of natural origin.Phlorizin crude product is placed in stainless steel cauldron, and the simple refining filtering of strong alkali solution being dissolved in 5% obtains phlorizin salts solution, proceeds to jacketed enamel reaction still, and adds Lewis acid and metal catalyst at low temperatures, about 35 DEG C of reaction 10-15h.Be cooled to 0 DEG C of crystallization again, filter, deionized water wash obtains Phloretin coarse-grain.This coarse-grain again with 95% dissolve with ethanol solution, essence filter, concentrate and crystallization of lowering the temperature, filter, obtain the high quality Phloretin fine work that content and purity are all greater than 99.0% after drying.This technique is applicable to large industrial production.
Description
Technical field
The present invention relates to and a kind of there is the semi-synthetic of anti-skin tumour and the cosmetic material medicine Phloretin that prevents brown pigments from generating, natural polyphenol one phlorizin being specifically related to that synthesis material is apple, extracting in apple bark and leaf, desugar under strong lewis acid and metal catalysis conditions, obtains Phloretin through separation and purification again.
Background technology
Phloretin, chemical name 3-(4-hydroxy phenyl)-1-(2,4,6-trihydroxy-phenyl)-1-acetone, it is a kind of olefinically unsaturated carboxylic acid derivatives of poly-hydroxy phenols, there is the various active such as anti-oxidant, antiultraviolet, prevent diabetes, antimicrobial and anti-skin carcinoma, especially preventing brown pigments from assembling and generating, show in anti-skin tumour and be greatly better than other this type of natural radioactivities.This is also one of senior whitening in recent years and the most frequently used composition of antiultraviolet class makeup, and the consumption of the annual Phloretin in the whole world is not less than 20 tons.And along with the increasing of its active exploration work, and at makeup with other are as the popularization of application in healthcare products, the consumption of annual Phloretin is made probably to increase with the speed of 20%.But then, the supply of natural Phloretin is that supply falls short of demand always, this product also along with raw-material price increase cost also climbs up and up.So exploitation or explore the new natural resource of Phloretin and preparation method is very important work, the value of its economic aspect is self-evident especially.
Current Phloretin is extraction and isolation from apple, apple bark and Folium Mali pumilae and obtains.But in these natural resource, Phloretin content is all not high on the one hand; On the other hand, renewable lasting and in large supply apple price is higher, and apple bark and fresh apple leaf are the resource of unsustainable regeneration.This just greatly limit the market supply of Phloretin.And the yield of its derivative phlorizin obtained from extraction and isolation from apple, apple bark and Folium Mali pumilae together with Phloretin be the 5-10 of Phloretin doubly, Phloretin in chemical structure be exactly than phlorizin in the 4-position of parent nucleus polyhydroxy phenol few sugared ring.
So it is feasible that the phlorizin utilizing cost lower, in plentiful supply prepares Phloretin.Utilize the desugar of glucosides class natural product to prepare aglycon and have chemical method and biological enzyme.Biological enzyme, if polydatin is under glucuroide effect, generates oxidation-resistant active ingredient trans-resveratrol, the industrialization of this production technique.Chemical method as prepared slimming health product luteolin from rutin and Hesperidin under highly basic and catalyst action.Patent system of the present invention is chemical method for Phloretin technique, and under strong lewis acid and metal catalyst effect, phlorizin desugar generates Phloretin.
The present invention prepares Phloretin and above-mentioned difference is:
(1) with the thick product of natural phlorizin for raw material, wherein the source of phlorizin is natural product.
(2) this technique is that chemically is semi-synthetic with phlorizin, avoids large-scale extracting and developing, purge process, easily controls from production cost and environmentally friendly aspect.
(3) the semi-synthetic scale at production unit of chemical method and quantitatively than extracting directly investment few, simple to operate, producers are required low.
(4) semi-synthesis method has separation and purification operation to raw material and product in process processed, and the finished product purifying process is simple, and quality product is better than natural extract Phloretin purity, content is higher.
(5) reaction scale is little, and chemical principle auxiliary material uses few, is all recycle and environmental friendliness mostly.Present invention process is the route of excellent suitability for industrialized production from economy, environment and Occupational health angle.
Summary of the invention
The present invention needs the key problem solved to be prepare in semi-synthetic mode the natural extract Phloretin that Phloretin substitutes current industrialized high cost, high investment completely, sets up the semi-synthetic industrialization process from phlorizin to Phloretin of environmental friendliness, low cost, high purity, high-content.
Object of the present invention is achieved through the following technical solutions, and concrete route is shown in Figure of description.
The semi-synthesizing technology route of Phloretin is with phlorizin crude product for raw material, through simple purification phlorizin, then strong lewis acid and metal catalytic desugar unit and crystallization recrystallization obtain high-content and highly purified product.
Concrete steps are as follows:
(1) with the alkaline aqueous solution of 5-10 times of volume, pH value, about 11, is dissolved phlorizin crude product, after stirring at room temperature 1h, is filtered removing insoluble impurities, obtain the better phlorizin sodium-salt aqueous solution of purity.
(2) at above-mentioned phlorizin sodium-salt aqueous solution, pass into enamel reaction still, icy salt solution is cooled to less than 5 DEG C, slowly add strong lewis acid and metal catalyst again, pH value controls at 1-2, is slowly warming up to 35 DEG C, continue stir about 10-15h, thin-layer chromatography is observed phlorizin spot and is disappeared.
(3) reacted, temperature has been down to 0 DEG C, continued to stir, have Phloretin crystal to separate out in process, filtration under diminished pressure, and with a small amount of deionized water wash, obtain Phloretin crude product.
(4) by Phloretin coarse-grain with a certain amount of 95% ethanol heating for dissolving, cross secondary filter to crystallizer, concentrating under reduced pressure goes out certain volume ethanol, then cooling crystallization, filters.Obtain product and obtain fine work with bipyramid drying oven dry, content and purity are greater than 99.0%.
The invention provides the industrialized preparing process of semi-synthetic Phloretin, with natural phlorizin for Material synthesis Phloretin.Reaction system is simple, flow process is controlled, production environmental protection, efficiency are high.
Accompanying drawing illustrates:
Accompanying drawing is the semi-synthetic route of Phloretin.
Embodiment:
Further illustrate the present invention in the following embodiments, this does not limit the scope of the invention.
The synthesis of embodiment 1 Phloretin
Phlorizin crude product 50.0kg (phlorizin content about 90%), in 500L stainless steel cauldron, adds the sodium hydroxide solution about 300 liters of 5%, stirring at room temperature makes phlorizin dissolve, after about 1h, vacuum filters, and filtrate goes to an other 500L enamel reaction still.Stir and in chuck, pass into icy salt solution cooling, when reactor temperature is down to less than 5 DEG C, slowly add boron trifluoride ether solution and be about 1.9L, pH value is about about 1.5, and process control temp is not higher than 10 DEG C.Then continue disposablely to add Nickel dichloride hexahydrate 0.6kg, and be warming up to 35 DEG C gradually, stirring reaction 12h, thin-layer chromatography monitoring phlorizin spot disappears, and is considered as reaction and completes.After reaction terminates, then be cooled to 0 DEG C, continue to stir, Phloretin crystal is separated out gradually, after about 2h, and filtration under diminished pressure, and with a small amount of deionized water wash, obtain Phloretin crude product.
The synthesis of embodiment 2 Phloretin
Phlorizin crude product 50.0kg (phlorizin content about 90%), in 500L stainless steel cauldron, adds the sodium hydroxide solution about 300 liters of 5%, stirring at room temperature makes phlorizin dissolve, after about 1h, vacuum filters, and filtrate goes to an other 500L enamel reaction still.Stir and in chuck, pass into icy salt solution cooling, when reactor temperature is down to less than 5 DEG C, slowly add phosphorus tribromide and be about 1.6L, pH value is about about 1, and process control temp is not higher than 10 DEG C.Then continue disposablely to add iron trichloride 0.4kg, and be warming up to 35 DEG C gradually, stirring reaction 15h, thin-layer chromatography monitoring phlorizin spot disappears, and is considered as reaction and completes.After reaction terminates, then be cooled to 0 DEG C, continue to stir, Phloretin crystal is separated out gradually, after about 2h, and filtration under diminished pressure, and with a small amount of deionized water wash, obtain Phloretin crude product.
Embodiment 3 Phloretin is refined
By moisture for Phloretin coarse-grain weight in wet base 40.0kg with 400L content 95% ethanolic soln heating for dissolving, cross secondary filter to 500L stainless steel crystallizer, concentrating under reduced pressure goes out 300L ethanol, then is cooled to 10 DEG C of crystallizatioies while stirring, filters after 2h.Dry 2h with bipyramid drying again and obtain benzfluorenol fine work 31.0kg, content and purity are greater than 99.0%.
Claims (3)
1. prepare whitening, prevent and treat the method for skin carcinoma active skull cap components Phloretin for one kind, with the phlorizin of natural extract for raw material, Phloretin is obtained through chemical method degraded, it is characterized by: with content about 90% phlorizin crude material, to dissolve phlorizin under the strong base solution room temperature of the 3-5% of 5-10 times of volume, this quasi-alkali is selected from sodium hydroxide, potassium hydroxide mineral alkali; Phlorizin dissolving crude product is after strong base solution, and suction filtration removes insoluble impurities, and now solution ph is about 11; Alkalescence is proceeded to enamel reaction still containing phlorizin filtrate, pass into icy salt solution and be cooled to less than 5 DEG C, add strong lewis acid and metal catalyst, acid adding temperature controls within 10 DEG C, then 35 DEG C of reaction 10-15h are warming up to, disappear until thin-layer chromatography detects raw material phlorizin spot, be considered as reaction and complete;
Described strong lewis acid is selected from boron trifluoride diethyl etherate, trimethylchlorosilane, phosphorus tribromide, aluminum chloride;
Described metal catalyst is selected from Nickel dichloride hexahydrate, iron(ic) chloride, cupric chloride.
2. method according to claim 1, after it is characterized in that reaction completes, then is cooled to 0 DEG C with icy salt solution, and continue stirring and crystallizing 2h, suction filtration obtains Phloretin crude product, and with a small amount of deionized water wash, obtains Phloretin coarse-grain and filters solid carbon dioxide and divide and wait to refine.
3. method according to claim 2, it is characterized in that Phloretin coarse-grain is with 10 times amount 95% ethanol heating for dissolving, cross secondary filter to crystallizer, concentrating under reduced pressure goes out about 7.5 times of volume ethanol, cooling crystallization again, suction filtration, obtain product and obtain fine work with bipyramid drying oven dry, content and purity are greater than 99.0%.
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