CN109970608B - Hydroxytyrosol thiodipropionate with antioxidant activity and synthesis method thereof - Google Patents
Hydroxytyrosol thiodipropionate with antioxidant activity and synthesis method thereof Download PDFInfo
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- JUUBCHWRXWPFFH-UHFFFAOYSA-N Hydroxytyrosol Chemical compound OCCC1=CC=C(O)C(O)=C1 JUUBCHWRXWPFFH-UHFFFAOYSA-N 0.000 title claims abstract description 110
- 235000003248 hydroxytyrosol Nutrition 0.000 title claims abstract description 76
- 229940095066 hydroxytyrosol Drugs 0.000 title claims abstract description 76
- 230000003078 antioxidant effect Effects 0.000 title abstract description 13
- 238000001308 synthesis method Methods 0.000 title abstract description 5
- ODJQKYXPKWQWNK-UHFFFAOYSA-L 3-(2-carboxylatoethylsulfanyl)propanoate Chemical compound [O-]C(=O)CCSCCC([O-])=O ODJQKYXPKWQWNK-UHFFFAOYSA-L 0.000 title description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 52
- -1 hydroxytyrosol thiodipropionate compound Chemical class 0.000 claims abstract description 44
- 239000012043 crude product Substances 0.000 claims abstract description 31
- ODJQKYXPKWQWNK-UHFFFAOYSA-N 3,3'-Thiobispropanoic acid Chemical compound OC(=O)CCSCCC(O)=O ODJQKYXPKWQWNK-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000003490 Thiodipropionic acid Substances 0.000 claims abstract description 27
- 235000019303 thiodipropionic acid Nutrition 0.000 claims abstract description 27
- 239000011347 resin Substances 0.000 claims abstract description 21
- 229920005989 resin Polymers 0.000 claims abstract description 21
- 235000013305 food Nutrition 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 11
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- 230000009471 action Effects 0.000 claims abstract description 3
- 239000002994 raw material Substances 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 81
- 239000003480 eluent Substances 0.000 claims description 28
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 13
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- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 3
- 229940118019 malondialdehyde Drugs 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
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- 231100000315 carcinogenic Toxicity 0.000 description 2
- MGJZITXUQXWAKY-UHFFFAOYSA-N diphenyl-(2,4,6-trinitrophenyl)iminoazanium Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1N=[N+](C=1C=CC=CC=1)C1=CC=CC=C1 MGJZITXUQXWAKY-UHFFFAOYSA-N 0.000 description 2
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- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 2
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- JKDRLGCUTJVKCE-UHFFFAOYSA-N 4-hydroxynonanal Chemical compound CCCCCC(O)CCC=O JKDRLGCUTJVKCE-UHFFFAOYSA-N 0.000 description 1
- RFWGABANNQMHMZ-UHFFFAOYSA-N 8-acetoxy-7-acetyl-6,7,7a,8-tetrahydro-5H-benzo[g][1,3]dioxolo[4',5':4,5]benzo[1,2,3-de]quinoline Natural products CC=C1C(CC(=O)OCCC=2C=C(O)C(O)=CC=2)C(C(=O)OC)=COC1OC1OC(CO)C(O)C(O)C1O RFWGABANNQMHMZ-UHFFFAOYSA-N 0.000 description 1
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- HKVGJQVJNQRJPO-UHFFFAOYSA-N Demethyloleuropein Natural products O1C=C(C(O)=O)C(CC(=O)OCCC=2C=C(O)C(O)=CC=2)C(=CC)C1OC1OC(CO)C(O)C(O)C1O HKVGJQVJNQRJPO-UHFFFAOYSA-N 0.000 description 1
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- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- RFWGABANNQMHMZ-HYYSZPHDSA-N Oleuropein Chemical compound O([C@@H]1OC=C([C@H](C1=CC)CC(=O)OCCC=1C=C(O)C(O)=CC=1)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RFWGABANNQMHMZ-HYYSZPHDSA-N 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
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- 210000003743 erythrocyte Anatomy 0.000 description 1
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- 239000003574 free electron Substances 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
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- 235000013622 meat product Nutrition 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000011576 oleuropein Nutrition 0.000 description 1
- RFWGABANNQMHMZ-CARRXEGNSA-N oleuropein Natural products COC(=O)C1=CO[C@@H](O[C@H]2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O)C(=CC)[C@H]1CC(=O)OCCc3ccc(O)c(O)c3 RFWGABANNQMHMZ-CARRXEGNSA-N 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002530 phenolic antioxidant Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
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- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
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- 230000001737 promoting effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L3/00—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs
- A23L3/34—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by treatment with chemicals
- A23L3/3454—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by treatment with chemicals in the form of liquids or solids
- A23L3/3463—Organic compounds; Microorganisms; Enzymes
- A23L3/3535—Organic compounds containing sulfur
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/53—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated and containing rings
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
The invention discloses a hydroxytyrosol thiodipropionate compound with antioxidant activity and a synthesis method thereof. The compound takes hydroxytyrosol and thiodipropionic acid as raw materials to react in an organic solvent under the action of a dehydrating agent, and the obtained crude product is absorbed and purified by macroporous resin. The hydroxytyrosol thiodipropionate compound can be used for protecting the color of food, preventing the oxidative discoloration of the food and preventing the flavor and quality of the food from being reduced due to oxidation, and has auxiliary and reinforcing effects on fat-soluble antioxidants added in water-containing oil or emulsified food. The method has the advantages of mild reaction conditions, high reaction yield, small pollution in the reaction process and suitability for industrial production.
Description
Technical Field
The invention relates to a hydroxytyrosol thiodipropionate compound with antioxidant activity and a synthesis method thereof, belonging to the technical field of antioxidant additives.
Background
With the wide concern on food quality and safety at home and abroad, it is important to prevent food from going bad and ensure human health. Oxidation is one of the main causes of food spoilage, and is mainly caused by oxidation of food by air, light and heat during storage and transportation. The oil is oxidized and rancid to generate peculiar smell, and the product peroxide in the rancid process has destructive effect on human enzyme systems and carcinogenic toxicity; the oxidation of cooked meat product not only reduces color, fragrance, taste and nutrition, but also produces harmful peroxide for human body and harmful substances such as hexanal, 4-hydroxynonanal, malondialdehyde, etc., wherein Malondialdehyde (MDA) has carcinogenic toxicity. In order to improve the oxidation resistance of food, the oxidation of food, especially grease, is prevented mainly by adding antioxidant into food except for physical methods such as low temperature, light shielding and vacuum. At present, the research on the artificial synthesis and semi-synthesis of the antioxidant is more and more focused by people and has wide application.
Hydroxytyrosol is a bioactive substance extracted from olive oil, is a phenolic compound generated by hydrolysis of oleuropein, has high safety and wide pharmacological activity, and has antibacterial and antiinflammatory activity, antithrombotic and antitumor activity, strong antioxidant activity and biological activity for promoting generation of mitochondria. Research evidence has shown that hydroxytyrosol can repair DNA damage and cell membrane damage caused by hydrogen peroxide in human red blood cells; can also relieve the nerve cell damage of mice caused by ferrous ions and NO, reduce the lipid oxidation level of the mitochondrial membrane and protect the mitochondrial membrane. Meanwhile, the hydroxytyrosol also has the function of resisting lipid oxidation, so that the hydroxytyrosol can be used as a novel food additive for the production of vegetable oil, thereby achieving the effect of prolonging the shelf life of the vegetable oil.
Thiodipropionic acid is an important polymer material auxiliary agent, and is usually used together with a phenolic antioxidant to produce a synergistic effect. Can be used as antioxidant of oil and fat in food field, and can effectively decompose hydroperoxide in oil and fat auto-oxidation chain reaction, thereby interrupting the chain reaction and improving the storage life of oil and fat. And can also be used as an anti-aging agent of polypropylene rubber or a heat stabilizer of polyvinyl chloride ether.
Disclosure of Invention
The invention aims to provide a hydroxytyrosol thiodipropionate compound which is used as a novel antioxidant and applied to the fields of medicines, health-care products and foods.
Hydroxytyrosol thiodipropionate compound shown in a structural formula (I),
the synthetic method of the compound comprises the following steps:
hydroxytyrosol and thiodipropionic acid are used as raw materials to react in an organic solvent under the action of a dehydrating agent, inert gas is adopted for protection in the reaction process, and after the reaction is finished, a crude product is adsorbed and purified by macroporous resin to obtain the hydroxytyrosol thiodipropionate compound.
The organic solvent is selected from acetonitrile, THF or DMF, preferably DMF.
The dehydrating agent is selected from DCC, concentrated sulfuric acid or EDC, preferably DCC.
The macroporous resin is selected from non-polar macroporous resin HP-20 type, XAD-2 type or D-101 type, preferably D-101 type.
The molar ratio of hydroxytyrosol to thiodipropionic acid is 2: 1-2.2: 1, and preferably 2.2: 1.
The reaction temperature is 50-60 ℃, and the reaction time is 8-10 hours.
The synthesis method comprises the following reaction steps:
(1) dissolving hydroxy tyrosol and thiodipropionic acid in a molar ratio of 2: 1-2.2: 1 in acetonitrile, THF or DMF, adding a dehydrating agent, and carrying out ultrasonic reaction at 50-60 ℃ for 8-10 hours under the protection of inert gas;
(2) tracking the reaction to be complete by thin-layer chromatography, stopping heating, and concentrating the mixture under reduced pressure to obtain a crude product of the hydroxytyrosol thiodipropionate compound;
(3) dissolving the crude product of the hydroxytyrosol thiodipropionate compound by using methanol, carrying out adsorption separation and purification by using a macroporous resin column, and eluting and enriching by using a methanol/water mixed solvent as an eluent to obtain the pure product of the hydroxytyrosol thiodipropionate compound.
The dehydrating agent in the step (1) is selected from DCC, concentrated sulfuric acid or EDC.
The eluent in the step (3) is a solution of methanol and water in a volume ratio of 1: 1.
According to the invention, hydroxytyrosol is structurally modified by thiodipropionic acid, so that a hydroxytyrosol thiodipropionate compound is obtained, the antioxidant activity of the compound is verified by explaining the synthetic method of the compound and combining a preliminary antioxidant experiment on the compound, and a novel antioxidant additive is expected to be provided and applied to the fields of foods, medicines and health care products.
Drawings
FIG. 1 shows the result of DPPH radical scavenging experiment.
Detailed description of the preferred embodiments
The invention will be further illustrated with reference to specific examples. These examples are for illustrative purposes only and do not limit the scope and spirit of the present invention.
Example 1
Preparation of compound bis (3, 4-dihydroxyphentyl) 3,3' -thiodipropanoate
Placing 95mg (0.62mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid in a 100mL reactor, adding 50mL of DMF to fully dissolve, adding 115mg (0.56mmol) of DCC into the reactor, introducing nitrogen to protect, and carrying out ultrasonic reaction for 8h at 60 ℃. The thin layer chromatography followed the reaction to completion, the heating was stopped and the protection device was removed. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And (3) further adsorbing and purifying the crude product by using macroporous resin D-101, wherein methanol: and (2) taking water =1:1 as an eluent, and concentrating and drying the eluent under reduced pressure to obtain 73.6mg of a refined hydroxytyrosol thiodipropionate compound with the total yield of 58.4%.
1H-NMR (400MHz, DMSO-d 6) δ (ppm): 9.15 (4H, s), 7.87 (1H, s), 7.52 (1H, d), 7.18 (1H, d), 6.74~6.52 (2H, m), 5.33 (1H, d), 4.63~4.62 (4H, m), 2.75~2.71 (4H, m), 2.15 (4H, m), 1.94~1.91 (4H, m);
113C-NMR (75MHz, DMSO-d 6) δ (ppm): 174.73, 145.37, 143.79, 130.74, 119.90, 116.77, 115.87, 63.07, 34.55, 28.64; MS (ESI) for (M+H)+:451.1。
Example 2
Putting 95mg (0.62mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid into a 100mL reactor, adding 50mL of acetonitrile to fully dissolve, adding 115mg (0.56mmol) of DCC into the reactor, introducing nitrogen to protect, carrying out ultrasonic reaction for 10h at 50 ℃, stopping heating, and removing a protection device. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And (3) further adsorbing and purifying the crude product by using macroporous resin D-101, wherein methanol: and (3) taking water =2:1 as an eluent, and concentrating and drying the eluent under reduced pressure to obtain 55.1mg of a refined hydroxytyrosol thiodipropionate compound with the total yield of 43.7%.
Example 3
95mg (0.62mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid are placed in a 100mL reactor, 50mL of DMF is added to fully dissolve, 110mg (0.6mmol) of EDC is added into the reactor, nitrogen is introduced for protection, and ultrasonic reaction is carried out for 8h at 60 ℃. The thin layer chromatography followed the reaction to completion, the heating was stopped and the protection device was removed. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And (3) further adsorbing and purifying the crude product by using macroporous resin D-101, wherein methanol: and (3) taking water =1:2 as an eluent, and concentrating and drying the eluent under reduced pressure to obtain 49.2mg of a refined hydroxytyrosol thiodipropionate compound with the total yield of 39.0%.
Example 4
86mg (0.56mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid are placed in a 100mL reactor, 50mL of THF is added for full dissolution, 115mg (0.56mmol) of DCC is added into the reactor, nitrogen is introduced for protection, and ultrasonic reaction is carried out for 8h at 60 ℃. The thin layer chromatography followed the reaction to completion, the heating was stopped and the protection device was removed. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And (3) further adsorbing and purifying the crude product by using macroporous resin D-101, wherein methanol: and (3) taking water =2:1 as an eluent, and concentrating and drying the eluent under reduced pressure to obtain 58.6mg of a refined hydroxytyrosol thiodipropionate compound with the total yield of 46.5%.
Example 5
Placing 95mg (0.62mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid in a 100mL reactor, adding 50mL of acetonitrile to fully dissolve, adding 5mL of concentrated sulfuric acid into the reactor, introducing nitrogen to protect, and carrying out ultrasonic reaction at 60 ℃ for 8 h. The thin layer chromatography followed the reaction to completion, the heating was stopped and the protection device was removed. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And (3) further adsorbing and purifying the crude product by using macroporous resin D-101, wherein methanol: water =1:1 as eluent, and concentrating and drying the eluent under reduced pressure to obtain the refined hydroxytyrosol thiodipropionate compound of 40.7mg with the total yield of 32.3 percent.
Example 6
95mg (0.62mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid are placed in a 100mL reactor, 50mL of DMF is added to fully dissolve, 115mg (0.56mmol) of DCC is added into the reactor, nitrogen is introduced to protect, and ultrasonic reaction is carried out for 8h at 50 ℃. The thin layer chromatography followed the reaction to completion, the heating was stopped and the protection device was removed. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And further adsorbing and purifying the crude product by using macroporous resin HP-20, taking methanol as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating under reduced pressure to obtain a refined hydroxytyrosol thiodipropionate compound product of 38.6mg with the total yield of 30.6%.
Example 7
95mg (0.62mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid are placed in a 100mL reactor, 50mL of acetonitrile is added to fully dissolve the hydroxytyrosol and the thiodipropionic acid, 57.8mg (0.28mmol) of DCC is added into the reactor, nitrogen is introduced to protect the DCC, and the ultrasonic reaction is carried out for 8 hours at 50 ℃. The thin layer chromatography followed the reaction to completion, the heating was stopped and the protection device was removed. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And (3) further adsorbing and purifying the crude product by using macroporous resin XAD-2, wherein methanol: and (3) taking water =4:1 as an eluent, and concentrating and drying the eluent under reduced pressure to obtain 52.7mg of a refined hydroxytyrosol thiodipropionate compound with the total yield of 41.8%.
Example 8
86mg (0.56mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid are placed in a 100mL reactor, 50mL of acetonitrile is added to fully dissolve the hydroxytyrosol and the thiodipropionic acid, 115mg (0.56mmol) of DCC is added into the reactor, nitrogen is introduced to the reactor for protection, and the ultrasonic reaction is carried out for 10 hours at the temperature of 60 ℃. The thin layer chromatography followed the reaction to completion, the heating was stopped and the protection device was removed. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And (3) further adsorbing and purifying the crude product by using macroporous resin D-101, wherein methanol: water =1:1 as eluent, and the eluent is decompressed, concentrated and dried to obtain refined hydroxytyrosol thiodipropionate compound 66.9mg with the total yield of 53.1%.
Example 9
95mg (0.62mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid are placed in a 100mL reactor, 50mL of DMF is added to fully dissolve, 106mg (0.56mmol) of EDC is added into the reactor, nitrogen is introduced for protection, and ultrasonic reaction is carried out for 10h at 60 ℃. The thin layer chromatography followed the reaction to completion, the heating was stopped and the protection device was removed. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And (3) further adsorbing and purifying the crude product by using macroporous resin D-101, wherein methanol: water =1:1 as eluent, and the eluent is decompressed, concentrated and dried to obtain 57.0mg of refined hydroxytyrosol thiodipropionate compound with the total yield of 45.2%.
Example 10
95mg (0.62mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid are placed in a 100mL reactor, 50mL of THF is added to fully dissolve, 106mg (0.56mmol) of EDC is added into the reactor, nitrogen is introduced for protection, and ultrasonic reaction is carried out for 8h at 60 ℃. The thin layer chromatography followed the reaction to completion, the heating was stopped and the protection device was removed. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And (3) further adsorbing and purifying the crude product by using macroporous resin HP-20, wherein methanol: and (3) taking water =4:1 as an eluent, and concentrating and drying the eluent under reduced pressure to obtain 36.2mg of a refined hydroxytyrosol thiodipropionate compound with the total yield of 28.7%.
Example 11
Placing 95mg (0.62mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid in a 100mL reactor, adding 50mL of acetonitrile to fully dissolve, adding 5mL of concentrated sulfuric acid into the reactor, introducing nitrogen to protect, and carrying out ultrasonic reaction at 60 ℃ for 8 h. The thin layer chromatography followed the reaction to completion, the heating was stopped and the protection device was removed. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And (3) further adsorbing and purifying the crude product by using macroporous resin XAD-2, wherein methanol: and (2) taking water =1:1 as an eluent, and concentrating and drying the eluent under reduced pressure to obtain 45.2mg of a refined hydroxytyrosol thiodipropionate compound with the total yield of 35.9%.
Example 12
86mg (0.56mmol) of hydroxytyrosol and 50mg (0.28mmol) of thiodipropionic acid are placed in a 100mL reactor, 50mL of DMF is added to fully dissolve, 110mg (0.6mmol) of EDC is added into the reactor, nitrogen is introduced for protection, and ultrasonic reaction is carried out at 60 ℃ for 8 h. The thin layer chromatography followed the reaction to completion, the heating was stopped and the protection device was removed. And carrying out reduced pressure concentration on the reaction mixed system to obtain a crude product of the hydroxytyrosol thiodipropionate compound. And (3) further adsorbing and purifying the crude product by using macroporous resin D-101, wherein methanol: water =1:1 as eluent, and the eluent is decompressed, concentrated and dried to obtain refined hydroxytyrosol thiodipropionate compound 48.4mg with the total yield of 38.4%.
EXAMPLE 13 DPPH radical scavenging experiments
The experimental principle is as follows: in DPPH molecule, multiple electron-withdrawing-NO molecules exist2And a large pi bond of a benzene ring, so that a nitrogen radical can exist stably. The ethanol solution is purple, and has a maximum absorption peak at 517 nm. After the antioxidant is added, DPPH captures an electron to be paired with a free electron, the purple fades and becomes a yellow substance, the absorption at 517nm disappears, and the fading degree is in quantitative relation with the number of the accepted electrons. According to the principle, a spectrophotometer is used for detecting the change of the light absorption value after the DPPH free radical reacts with the sample liquid, so that the oxidation resistance of the sample for providing hydrogen atoms and removing free radicals can be detected.
The experimental method comprises the following steps:
(a) preparation of a DPPH test solution: accurately weigh oneQuantitative 1, 1-diphenyl-2-picrylhydrazyl radical, dissolved in methanol to 2X 10-4And (3) storing the DPPH solution in mol/L in a dark place.
(b) Preparing a solution to be detected: vc (positive control), hydroxytyrosol thiodipropionate compound (sample), hydroxytyrosol (control), thiodipropionic acid (control), and a mixed solution (control) of hydroxytyrosol and thiodipropionic acid, wherein the sample solution is subjected to gradient dilution by using methanol, and 4 groups of controls are respectively dissolved in a test tube by using a certain amount of methanol to prepare a concentration gradient which is the same as that of the sample. Corresponding 4 sets of control solutions were obtained (gradient setup see table 1).
(c) The operation method comprises the following steps:
and (3) measuring the absorbance of the sample solution: 2mL of sample solution (Table 1A) was added at a concentration of 2X 10-42mL of DPPH solution in mol/L, uniformly mixing, reacting for 30min in the dark at room temperature, adjusting to zero by methanol, measuring the absorbance Ai at 517nm, and simultaneously measuring the absorbance Aj after 2mL of methanol is mixed with 2mL of sample solution and the absorbance Ao after 2mL of DPPH solution is mixed with 2mL of methanol (the experimental results are shown in Table 2).
And (3) measuring the absorbance of the reference substance: 2mL of the control solution (Table 1 Vc, B, C, D) obtained in step (B) was added at a concentration of 2X 10-42mL of a DPPH solution in mol/L, uniformly mixing, reacting for 30min in the dark at room temperature, adjusting to zero with methanol, measuring the absorbance Ai at 517nm, and simultaneously measuring the absorbance Aj after mixing 2mL of methanol with 2mL of a control solution and the absorbance Ao after mixing 2mL of the DPPH solution with 2mL of methanol (the experimental results are shown in Table 2).
(d) Calculation of clearance rate: clearance (%) = [1- (Ai-Aj)/Ao ]. times.100%
As can be seen from the results of the experiments shown in tables 1 to 3 and FIG. 1, the hydroxytyrosol thiodipropionate compound (A) exhibited a significant effect of removing DPPH in a concentration-dependent manner. The clearance rate of the compound on DPPH is from 32.44% (1.648 mu g/mL) to 98.09% (1055 mu g/mL), the capability of the compound on DPPH of the compound (A) of hydroxytyrosol thiodipropionate is obviously better than that of single hydroxytyrosol (B), thiodipropionic acid (C) and a mixed solution (2: 1) (D) of hydroxytyrosol and thiodipropionic acid under the same concentration, and simultaneously, the clearance capability of the compound on DPPH of the compound (A) of hydroxytyrosol thiodipropionate is very close to or even better than that of a positive control Vc. The experimental results prove that the compound has excellent antioxidant activity and can be used as a novel antioxidant additive to be applied to the fields of food, medicine and health care products.
Claims (10)
1. Hydroxytyrosol thiodipropionate compound shown in a structural formula (I),
2. a method of synthesizing the compound of claim 1, wherein:
hydroxytyrosol and thiodipropionic acid are used as raw materials to react in an organic solvent under the action of a dehydrating agent, inert gas is adopted for protection in the reaction process, and after the reaction is finished, a crude product is adsorbed and purified by macroporous resin to obtain the hydroxytyrosol thiodipropionate compound.
3. The method of synthesis according to claim 2, characterized in that: the organic solvent is selected from acetonitrile, THF or DMF.
4. The method of synthesis according to claim 2, characterized in that: the dehydrating agent is selected from DCC, concentrated sulfuric acid or EDC.
5. The method of synthesis according to claim 2, characterized in that: the macroporous resin is selected from non-polar macroporous resin HP-20 type, XAD-2 type or D-101 type.
6. The method of synthesis according to claim 2, characterized in that: the molar ratio of the hydroxytyrosol to the thiodipropionic acid is 2: 1-2.2: 1.
7. The method of synthesis according to claim 2, characterized in that: the reaction temperature is 50-60 ℃, and the reaction time is 8-10 hours.
8. The synthesis process according to claim 2, characterized by comprising the following reaction steps:
(1) dissolving hydroxy tyrosol and thiodipropionic acid in a molar ratio of 2: 1-2.2: 1 in acetonitrile, THF or DMF, adding a DCC, concentrated sulfuric acid or EDC dehydrating agent, and carrying out ultrasonic reaction for 8-10 hours at 50-60 ℃ under the protection of inert gas;
(2) tracking the reaction to be complete by thin-layer chromatography, stopping heating, and concentrating the mixture under reduced pressure to obtain a crude product of the hydroxytyrosol thiodipropionate compound;
(3) dissolving the crude product of the hydroxytyrosol thiodipropionate compound by using methanol, carrying out adsorption separation and purification by using a macroporous resin column, and eluting and enriching by using a methanol/water mixed solvent as an eluent to obtain the pure product of the hydroxytyrosol thiodipropionate compound.
9. The method of synthesis according to claim 8, characterized in that: the eluent in the step (3) is a solution of methanol and water in a volume ratio of 1: 1.
10. Use of the hydroxytyrosol thiodipropionate compound according to claim 1 in the preparation of antioxidant additives for foods, medicines and health products.
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