CN114890972B - Method for preparing demethyl nobiletin by degrading nobiletin by microwave synergistic deep co-dissolution reagent - Google Patents
Method for preparing demethyl nobiletin by degrading nobiletin by microwave synergistic deep co-dissolution reagent Download PDFInfo
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- MRIAQLRQZPPODS-UHFFFAOYSA-N nobiletin Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC(=O)C2=C(OC)C(OC)=C(OC)C(OC)=C2O1 MRIAQLRQZPPODS-UHFFFAOYSA-N 0.000 title claims abstract description 63
- OBIOZWXPDBWYHB-UHFFFAOYSA-N Nobiletin Natural products C1=CC(OC)=CC=C1C1=C(OC)C(=O)C2=C(OC)C(OC)=C(OC)C(OC)=C2O1 OBIOZWXPDBWYHB-UHFFFAOYSA-N 0.000 title claims abstract description 62
- DOFJNFPSMUCECH-UHFFFAOYSA-N Demethylnobiletin Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC(=O)C2=C(O)C(OC)=C(OC)C(OC)=C2O1 DOFJNFPSMUCECH-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 45
- 238000000034 method Methods 0.000 title claims abstract description 45
- 238000004090 dissolution Methods 0.000 title claims abstract description 21
- 230000000593 degrading effect Effects 0.000 title claims abstract description 16
- 230000002195 synergetic effect Effects 0.000 title claims abstract description 10
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims abstract description 39
- 239000006184 cosolvent Substances 0.000 claims abstract description 17
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 claims abstract description 13
- 235000019743 Choline chloride Nutrition 0.000 claims abstract description 13
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 claims abstract description 13
- 229960003178 choline chloride Drugs 0.000 claims abstract description 13
- 235000006408 oxalic acid Nutrition 0.000 claims abstract description 13
- 238000002156 mixing Methods 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 15
- 239000007857 degradation product Substances 0.000 claims description 13
- 230000015556 catabolic process Effects 0.000 claims description 8
- 238000006731 degradation reaction Methods 0.000 claims description 8
- 238000002390 rotary evaporation Methods 0.000 claims description 5
- 238000005057 refrigeration Methods 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims 1
- 230000008020 evaporation Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 13
- 239000002253 acid Substances 0.000 abstract description 9
- 239000001257 hydrogen Substances 0.000 abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 9
- -1 hydrogen ions Chemical class 0.000 abstract description 6
- 239000003960 organic solvent Substances 0.000 abstract description 5
- 125000004430 oxygen atom Chemical group O* 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 4
- 239000012445 acidic reagent Substances 0.000 abstract description 2
- 230000009977 dual effect Effects 0.000 abstract description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 2
- 239000001301 oxygen Substances 0.000 abstract description 2
- 229910052760 oxygen Inorganic materials 0.000 abstract description 2
- 230000035484 reaction time Effects 0.000 abstract description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 229910021642 ultra pure water Inorganic materials 0.000 description 9
- 239000012498 ultrapure water Substances 0.000 description 9
- 238000000926 separation method Methods 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000000120 microwave digestion Methods 0.000 description 6
- 229910052796 boron Inorganic materials 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- CQIUKKVOEOPUDV-IYSWYEEDSA-N antimycin Chemical compound OC1=C(C(O)=O)C(=O)C(C)=C2[C@H](C)[C@@H](C)OC=C21 CQIUKKVOEOPUDV-IYSWYEEDSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- CQIUKKVOEOPUDV-UHFFFAOYSA-N citrinine Natural products OC1=C(C(O)=O)C(=O)C(C)=C2C(C)C(C)OC=C21 CQIUKKVOEOPUDV-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- MRXFJHKMONZNHG-UHFFFAOYSA-N Nor-Nobiletin Natural products C1=C(O)C(O)=CC=C1C1=CC(=O)C2=C(O)C(O)=C(O)C(O)=C2O1 MRXFJHKMONZNHG-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000000370 acceptor Substances 0.000 description 2
- 230000002378 acidificating 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
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 229930003935 flavonoid Natural products 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000010025 steaming Methods 0.000 description 2
- SWWQQSDRUYSMAR-UHFFFAOYSA-N 1-[(4-hydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol;hydrochloride Chemical group Cl.C1=CC(O)=CC=C1CC1C2=CC(O)=C(O)C=C2CCN1 SWWQQSDRUYSMAR-UHFFFAOYSA-N 0.000 description 1
- UDOOPSJCRMKSGL-UHFFFAOYSA-N 3-(2-hydroxyphenyl)-1-phenylprop-2-en-1-one Chemical class OC1=CC=CC=C1C=CC(=O)C1=CC=CC=C1 UDOOPSJCRMKSGL-UHFFFAOYSA-N 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002555 anti-neurodegenerative effect Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000010227 chenpi Substances 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- FFHWGQQFANVOHV-UHFFFAOYSA-N dimethyldioxirane Chemical compound CC1(C)OO1 FFHWGQQFANVOHV-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 230000005496 eutectics Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000010815 organic waste Substances 0.000 description 1
- 229930182496 polymethoxyflavone Natural products 0.000 description 1
- 230000003405 preventing effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for preparing demethyl nobiletin by degrading nobiletin through microwave synergistic deep co-dissolution reagent, and belongs to the technical field of preparation of demethyl nobiletin. The deep co-solvent reagent formed by the choline chloride and the oxalic acid has the dual functions of an organic solvent and an acidic reagent. The oxygen atoms of the 5-methoxyl group and the C-cyclocarbonyl group of the nobiletin have isolated oxygen atom pairs, and under the strong acid environment formed by the deep co-solvent reagent, a six-membered ring structure coordinated by proton-hydrogen and electron-donor-oxygen is easily formed, and the six-membered ring can be continuously hydrolyzed to become hydroxyl, so that the nobiletin is converted into the demethyl nobiletin after the 5-methoxyl group is removed. The invention utilizes microwaves to degrade, is convenient for hydrogen ions to attack the nobiletin, and thus prepares out the methyl nobiletin in a short time. Compared with the traditional acidolysis method, the method has high conversion efficiency and can control the reaction time to be about 20 minutes.
Description
Technical Field
The invention relates to the technical field of preparation of demethyl nobiletin, in particular to a method for preparing demethyl nobiletin by degrading nobiletin by using a microwave synergistic deep co-dissolution reagent.
Background
The demethyl nobiletin is a flavonoid, and has more powerful active functions than nobiletin, such as antioxidant, antiinflammatory, anticancer cell proliferation, anti-neurodegenerative disease and liver fibrosis preventing effects. However, the conversion rate of the dehydromethylation of the nobiletin under natural conditions is very low, and the use of the dehydromethylation of the nobiletin in functional foods and medicines is greatly limited due to the influence of factors such as storage temperature, humidity, microbial distribution and the like.
At present, the method for preparing the demethyl nobiletin by degrading the nobiletin is mainly an acidolysis method. Luo Shikun et al found that nornobiletin (Luo Shikun, wang Guhuan, xu Lanying, long Tao, & Li Shiming. Extraction and modification of nobiletin in pericarpium Citri Tangerinae. Food science, 2014 (24), 20-23.); chu et al prepared desmethyl nobiletin (Chu H W, wu H T, lee Y J. Regional electric hydrolysis of 2-hydroxychalcones by dimethyldioxirane towards polymethoxylated flavonoids, 2004,60 (11): 2647-2655) from boron tribromide, boron trichloride, aluminum trichloride and concentrated hydrochloric acid. However, hydrochloric acid is a volatile acid, which is poor in operability, and the use of hydrochloric acid and organic reagents easily corrodes production equipment, producing non-degradable acidic waste liquid to pollute the environment, and is disadvantageous for industrial production. Huang et al replace the highly corrosive acids with edible acids such as phosphoric acid, lactic acid and citric acid, but require high temperature conditions at 175 ℃ for conversion (Huang X, kouX, wang L, et al effective hydroxylation oftangeretin from Citrus Peel (Chenpi) by edible acids and its improvement in antioxidant and anti-liveactivity.lwt, 2019, 116:108469.) and this method requires a long high temperature heating process, is energy consuming and is less costly and safer. Therefore, an efficient, energy-saving and environment-friendly method for degrading nobiletin to prepare demethyl nobiletin is urgently needed.
Disclosure of Invention
The invention aims to provide a method for preparing demethyl nobiletin by degrading nobiletin by using a microwave synergistic deep co-dissolution reagent, which realizes high efficiency, green and environment protection, and does not generate organic and acidic waste liquid in the process.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a method for preparing demethyl nobiletin by degrading nobiletin with a microwave synergistic deep-dissolution reagent, which comprises the following steps:
mixing nobiletin and a deep co-solvent reagent, degrading the obtained mixture under the microwave condition, and separating to obtain the demethylated nobiletin; the deep co-solvent reagent is choline chloride and oxalic acid.
Preferably, the molar ratio of the choline chloride to the oxalic acid is 1:1.
Preferably, the concentration of the nobiletin in the deep-cosolvent reagent is 1-2 mg/mL.
Preferably, the power of the microwaves is 750-850W, and the temperature is 100-105 ℃.
Preferably, the degradation time is 15-20 min.
Preferably, the separation comprises mixing degradation products obtained by degradation with water, followed by refrigeration and centrifugation.
Preferably, the volume ratio of the water to the deep-eutectic agent is (10-12): 1.
Preferably, the temperature of the refrigeration is 4 ℃ and the time is 3-5 hours.
Preferably, after the separation, the method further comprises the step of performing rotary evaporation on the obtained liquid to obtain the deep co-solvent reagent.
Preferably, the temperature of the rotary steaming is 45 ℃.
The invention provides a method for preparing demethyl nobiletin by degrading nobiletin with a microwave synergistic deep-dissolution reagent, which comprises the following steps: and mixing the nobiletin and the deep co-solvent reagent, degrading the obtained mixture under the microwave condition, and separating to obtain the demethyl nobiletin. The deep co-solvent reagent formed by the choline chloride and the oxalic acid has the solubility of an organic solvent, and the concentration of hydrogen ions is higher than that of strong acids such as hydrochloric acid, sulfuric acid and the like, so that the deep co-solvent reagent has the dual functions of the organic solvent and the acidic reagent. The oxygen atoms of the 5-methoxyl group and the C-cyclocarbonyl group of the nobiletin have isolated oxygen atom pairs, and under the strong acid environment formed by the deep co-solvent reagent, a six-membered ring structure coordinated by proton-hydrogen and electron-donor-oxygen is easily formed, and the six-membered ring can be continuously hydrolyzed to become hydroxyl, so that the nobiletin is converted into the demethyl nobiletin after the 5-methoxyl group is removed. The invention utilizes microwaves to degrade, the penetrability of microwave energy can rapidly and uniformly heat reactants, and the porosity of the reactants is improved, so that the whole reaction system can be heated to about 100 ℃ in a short time, the probability of collision of polar molecules in the system is increased, meanwhile, the acting force among molecules in the system is enhanced, and hydrogen ions can attack the nobiletin conveniently, so that the methyl nobiletin can be prepared in a short time. Compared with the traditional acidolysis method, the method has high conversion efficiency and can control the reaction time to be about 20 minutes.
The deep eutectic agent used in the invention is a new generation of ionic liquid formed by hydrogen bond donors and hydrogen bond acceptors, and has the excellent properties of low cost, low toxicity, biodegradability and the like.
Compared with the traditional acidolysis method, the method for preparing the demethyl nobiletin by degrading the nobiletin by utilizing the microwave synergistic deep-dissolution reagent does not need long-time high-temperature heating treatment, is safe in operation and low in energy consumption cost, does not need to use organic solvents such as ethanol and the like, does not need to use strong corrosive inorganic acids such as concentrated hydrochloric acid and the like, does not need to use organic solvents, and the used deep-dissolution reagent can be recycled after separation, so that no acid and organic waste liquid are generated in the whole process, the method is green and environment-friendly, and provides guidance for preparing other demethyl polymethoxy flavones such as the demethyl nobiletin.
Furthermore, the invention utilizes water to separate out the methyl-Sichuan citrinin, and the water is not only an acceptor of hydrogen bonds but also a donor of hydrogen bonds, so that the stability of the deep-eutectic reagent is damaged by the addition of the water to reduce the solubility of the deep-eutectic reagent, the water solubility of the demethyl-Sichuan citrinin is poorer, precipitate can be separated out under the condition that the system stability is damaged, and after the precipitated demethyl-Sichuan citrinin is collected, the solution is distilled off to remove the water, and the deep-eutectic reagent can be recycled, so that no acid waste liquid is generated in the whole reaction process.
Drawings
FIG. 1 is a liquid chromatogram of standard substances of nobiletin and demethyl nobiletin;
FIG. 2 is a liquid chromatogram of nobiletin and desmethyl nobiletin in example 1;
FIG. 3 is a liquid chromatogram of nobiletin and desmethyl nobiletin in example 2;
FIG. 4 is a liquid chromatogram of nobiletin and desmethyl nobiletin in example 3;
FIG. 5 is a liquid chromatogram of nobiletin and desmethyl nobiletin in comparative example 1.
Detailed Description
The invention provides a method for preparing demethyl nobiletin by degrading nobiletin with a microwave synergistic deep-dissolution reagent, which comprises the following steps:
mixing nobiletin and a deep co-solvent reagent, degrading the obtained mixture under the microwave condition, and separating to obtain the demethylated nobiletin; the deep-solubilizing agent preferably comprises choline chloride and oxalic acid.
In the present invention, the preparation materials are commercially available as known to those skilled in the art unless otherwise specified.
The invention mixes the nobiletin and the deep-dissolving reagent. The source of the nobiletin is not particularly limited, and the nobiletin can be commercially available products well known in the art.
In the invention, the deep-dissolution reagent is choline chloride and oxalic acid; the molar ratio of the choline chloride to the oxalic acid is preferably 1:1; the preparation method of the deep-dissolution reagent preferably comprises the steps of mixing choline chloride and oxalic acid, and placing the mixture in a water bath at the temperature of 100 ℃ for stirring until a clear and transparent deep-dissolution reagent is formed; the stirring rate is not particularly limited in the present invention, and the materials can be uniformly mixed according to a process well known in the art.
In the invention, the concentration of the nobiletin in the deep-cosolvent reagent is preferably 1-2 mg/mL.
The process of mixing the nobiletin and the deep-dissolving reagent is not particularly limited, and the materials are uniformly mixed according to the process well known in the art.
After the mixing is completed, the obtained mixture is degraded under the microwave condition. In the invention, the power of the microwaves is preferably 750-850W, more preferably 800W, and the temperature is preferably 100-105 ℃ and more preferably 102 ℃; the degradation time is preferably 15 to 20min, more preferably 17min.
In the invention, the microwave digestion instrument used for microwaves is preferably a MARS 6240/50 type microwave digestion instrument of CEM company in America.
After the degradation is completed, the obtained product is separated; the separation preferably comprises mixing degradation products obtained by degradation with water, and sequentially refrigerating and centrifuging; the water is preferably ultrapure water; the volume ratio of water to the deep-solubilizing agent is preferably (10-12): 1, more preferably 11:1. The process of mixing the degradation product with water is not particularly limited in the present invention, and may be carried out according to a process well known in the art. The invention uses ultrapure water to separate out the demethyl nobiletin.
In the present invention, the temperature of the refrigeration is preferably 4℃and the time is preferably 3 to 5 hours.
The process of the centrifugal separation is not particularly limited, and may be performed according to a process well known in the art.
After the centrifugal separation is completed, the obtained precipitate is preferably washed to be neutral by ultrapure water and then freeze-dried to obtain the demethyl nobiletin. The washing and freeze-drying processes are not particularly limited in the present invention, and may be performed according to processes well known in the art.
After the centrifugal separation is completed, the method preferably further comprises the step of carrying out rotary evaporation on the obtained liquid, and collecting high-viscosity components to obtain the deep co-solvent reagent. In the present invention, the temperature of the rotary evaporation is preferably 45 ℃. The invention removes water in the liquid by rotary evaporation; the time of the spin-steaming is not particularly limited, and all the water in the liquid may be removed.
The technical solutions of the present invention will be clearly and completely described in the following in connection with the embodiments of the present invention. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
In the following examples, the microwave apparatus used was a MARS 6240/50 microwave digestion instrument from CEM company, USA.
Example 1
Mixing choline chloride and oxalic acid according to a molar ratio of 1:1, and placing the mixture in a water bath at 100 ℃ for stirring until a clear and transparent deep-dissolution reagent is formed;
dissolving 20mg of nobiletin pure product in 20mL of prepared deep co-dissolution reagent, uniformly mixing, putting the obtained mixture into a microwave digestion instrument, wherein the treatment condition is that the microwave power is 750W, the microwave temperature is 100 ℃, and the treatment time is 15min, so as to obtain degradation products;
adding 10 times of volume of ultrapure water to the degradation product, refrigerating the obtained mixture at 4 ℃ for 5 hours, centrifuging, washing the obtained precipitate with the ultrapure water to be neutral, and freeze-drying to obtain the demethyl nobiletin.
Example 2
Mixing choline chloride and oxalic acid according to a molar ratio of 1:1, and placing the mixture in a water bath at 100 ℃ for stirring until a clear and transparent deep-dissolution reagent is formed;
dissolving 40mg of nobiletin pure product in 20mL of prepared deep co-dissolution reagent, uniformly mixing, putting the obtained mixture into a microwave digestion instrument, wherein the treatment condition is that the microwave power is 800W, the microwave temperature is 102 ℃, and the treatment time is 17min, so as to obtain degradation products;
adding 11 times of volume of ultrapure water to the degradation product, refrigerating the obtained mixture at 4 ℃ for 5 times, centrifuging, washing the obtained precipitate with the ultrapure water to be neutral, and freeze-drying to obtain the demethyl nobiletin.
Example 3
Mixing choline chloride and oxalic acid according to a molar ratio of 1:1, and placing the mixture in a water bath at 100 ℃ for stirring until a clear and transparent deep-dissolution reagent is formed;
dissolving 20mg of nobiletin pure product in 20mL of prepared deep co-dissolution reagent, uniformly mixing, putting the obtained mixture into a microwave digestion instrument, wherein the treatment condition is that the microwave power is 800W, the microwave temperature is 105 ℃, and the treatment time is 20min, so as to obtain degradation products;
adding 12 times of volume of ultrapure water to the degradation product, refrigerating the obtained mixture at 4 ℃ for 5 times, centrifuging, washing the obtained precipitate with the ultrapure water to be neutral, and freeze-drying to obtain the demethyl nobiletin.
Comparative example 1
Traditional acidolysis method: catalyzing 20mg of nobiletin in 20mL of concentrated hydrochloric acid with the mass percentage of 37% for 12h, and keeping the reaction temperature at 90 ℃ all the time to obtain degradation products.
Result detection
1) Mixing 1mg of nobiletin standard substance and 1mg of demethyl nobiletin standard substance in 1mL of methanol, taking the obtained mixed solution as a standard sample, taking 500 mu L of the standard sample, and performing high performance liquid chromatography detection, wherein the high performance liquid chromatography detection process comprises the following steps:
sucking 500 mu L of sample, adding 500 mu L of chromatographic grade methanol, uniformly mixing, and passing through a 0.45 mu m nylon membrane for later use;
the detection equipment is Agilent 1260 Infinicity high performance liquid chromatograph, the chromatographic column model is Waters Atlantis T column (2.1X105 mm,1 μm), mobile phase A is glacial acetic acid of 0.1% (v/v), mobile phase B is acetonitrile, and the flow rate is 0.8mL/min;
the elution procedure was as follows: 0-2 min, 5-5% B; 2-10 min, 5-30% B; 10-12 min, 30-100% B; 12-18 min, 100-100% B; 18-20 min, 100-5% B; 20.00-25.00 min, 5-5%;
the column temperature is kept at 25 ℃, and the ultraviolet detection wavelength is 210nm; the results obtained are shown in FIG. 1; FIG. 1 is a chromatogram of a nobiletin standard and a nornobiletin standard; the peak time of nobiletin and desmethyl nobiletin is evident in FIG. 1.
2) The conversion of nobiletin and the production of desmethyl nobiletin in examples 1-3 were examined by high performance liquid chromatography as described in 1): the results obtained by taking the nobiletin-deep co-solvent reagent mixture and the deep co-solvent reagent mixed solution (namely degradation product) of the nobiletin after degradation in examples 1-3 as detection samples are shown in figures 2-4; meanwhile, the degradation product of comparative example 1 is subjected to high performance liquid chromatography detection, the obtained result is shown in fig. 5, and the result is analyzed as follows:
as shown in FIG. 2, in example 1, the nobiletin was almost completely converted into the desmethyl nobiletin, the conversion rate was 99.62%, and the treatment time was 15min, with high efficiency. As shown in FIG. 3, in example 2, almost all of the nobiletin was converted into desmethyl nobiletin, the conversion rate was 99.57%, and the treatment time was 17min, with high efficiency. As shown in FIG. 4, in example 3, almost all of the nobiletin was converted into desmethyl nobiletin, the conversion rate was 99.65%, and the treatment time was 20min, with high efficiency. Whereas comparative example 1 was reacted for 12 hours using the conventional acidolysis method, the conversion rate reached only 23.52%, demonstrating that the process of the present invention can significantly reduce the treatment time and increase the conversion rate.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (8)
1. A method for preparing demethyl nobiletin by degrading nobiletin with microwave synergistic deep-dissolution reagent comprises the following steps:
mixing nobiletin and a deep co-solvent reagent, degrading the obtained mixture under the microwave condition, and separating to obtain the demethylated nobiletin; the deep co-dissolution reagent is choline chloride and oxalic acid; the power of the microwaves is 750-850W, and the temperature is 100-105 ℃; the degradation time is 15-20 min.
2. The method according to claim 1, wherein the molar ratio of choline chloride to oxalic acid is 1:1.
3. the method according to claim 1, wherein the concentration of nobiletin in the deep-solubilizing reagent is 1-2 mg/mL.
4. The method of claim 1, wherein the separating comprises mixing degradation products from the degradation with water, and sequentially refrigerating and centrifuging.
5. The method of claim 4, wherein the volume ratio of water to deep co-solvent agent is (10-12): 1.
6. the method of claim 4, wherein the temperature of the refrigeration is 4 ℃ for 3 to 5 hours.
7. The method of claim 1, further comprising subjecting the resulting liquid to spin evaporation to provide a deep-eutectic reagent after the separating.
8. The method of claim 7, wherein the temperature of the rotary evaporation is 45 ℃.
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| CN114432294A (en) * | 2022-02-21 | 2022-05-06 | 天津商业大学 | 5-demethylnobiletin and preparation method and application thereof |
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| CN114432294A (en) * | 2022-02-21 | 2022-05-06 | 天津商业大学 | 5-demethylnobiletin and preparation method and application thereof |
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