Organic selenium compound and application thereof in preparation of antioxidant

Abstract

The invention provides an organic selenide. The organic selenide has a structure shown as the following I. The natural active compound sinapic acid is combined with the selenium element to synthesize the novel organic selenium compound, so that the blank of drug combination of a traditional Chinese medicine antioxidant activity structure and the selenium element is filled up, the antioxidant activity of the traditional Chinese medicine antioxidant activity structure and the selenium element generates a synergistic effect, and the safety and the antioxidant effect are improved; and the compound has huge potential in the aspects of preparing antioxidants, medicines for preventing and / or treating diseases caused by oxidative damage and the like.

Description

Technical Field

[0001] This invention belongs to the field of drug synthesis, specifically relating to a novel organoselenium compound and its synthesis method, as well as the application of this compound in the preparation of antioxidants. Background Technology

[0002] Many human diseases are closely related to oxidative damage. The mechanism involves the oxidative modification of biomolecules (such as DNA, proteins, and lipids) due to an imbalance between reactive oxygen species (ROS) and the antioxidant system. The molecular mechanisms include DNA damage, protein oxidation, and lipid peroxidation. Oxidative damage can cause numerous related diseases such as cardiovascular diseases, metabolic diseases, neurodegenerative diseases, inflammation, and tumors. Antioxidant enzymes play a crucial role in the human body's antioxidant defense system, with glutathione peroxidase being a core member. The trace element selenium is the active site of this enzyme.

[0003] Current research on selenium focuses on three forms: inorganic selenium, organic selenium, and nano-selenium. However, inorganic selenium suffers from significant toxicity and low bioavailability; nano-selenium is unstable; and organic selenium, mostly derived from plant or microbial transformations, has an unclear structure, making it difficult to use in new drug development. Therefore, developing structurally defined and effective organic selenium is a key focus in antioxidant drug research. On the other hand, traditional Chinese medicine contains abundant antioxidants such as alkaloids, flavonoids, and polyphenols, and studies have shown that these antioxidant components often promote selenium absorption. Therefore, combining selenium with natural products can not only leverage the antioxidant advantages of both but also achieve a synergistic effect, showing great potential in the prevention and treatment of diseases caused by oxidative damage. Summary of the Invention

[0004] To overcome the shortcomings in the existing field, this invention synthesizes a novel organoselenium compound with antioxidant effects. This compound has high safety and good antioxidant effect.

[0005] In a first aspect, the present invention provides an organoselenium compound having the structure shown in I below:

[0006]

[0007] The organoselenium compound provided by this invention combines selenium with sinapic acid, a monomer of traditional Chinese medicine, through chemical bonds to form a novel selenium-containing active molecule, enabling the two to exert a synergistic effect.

[0008] Secondly, the present invention provides a method for preparing the organoselenium compound.

[0009] The organoselenium compound of this invention is prepared using the following synthetic route:

[0010] (1)

[0011] (2)

[0012] (3)

[0013] As a preferred embodiment of the present invention, step (1) includes: taking selenium powder, mixing it with distilled water under nitrogen protection, slowly adding sodium borohydride aqueous solution while stirring, and after the system becomes clear, adjusting the pH of 2-chloroacetic acid to 9-10 with saturated sodium carbonate solution, adding it to the above reaction solution, and stirring at room temperature; collecting the reaction solution, adjusting the pH to 2-3 with dilute hydrochloric acid, extracting with ethyl acetate, collecting the organic phase, removing water, concentrating, recrystallizing, and obtaining 2,2'-selenodiacetic acid.

[0014] As a preferred embodiment of the present invention, step (2) includes: dissolving 2,2'-selenodiacetic acid in anhydrous tetrahydrofuran at -5 to 5°C under nitrogen protection, adding oxaloyl chloride dropwise, and then stirring the reaction at 38 to 42°C; evaporating the solvent in the reaction solution to obtain 2,2'-selenodiacetic chloride.

[0015] In a preferred embodiment of the present invention, step (3) includes: preparing an anhydrous tetrahydrofuran solution of sinapic acid under nitrogen protection, adding pyridine and pre-cooling in an ice bath; slowly adding an anhydrous tetrahydrofuran solution of 2,2'-selenodiacetyl chloride, and then stirring the reaction at 33-37°C; evaporating the reaction solution to dryness, reconstituted with ethyl acetate, washing with water, extracting and collecting the organic phase, removing water, concentrating, and obtaining crude product of 3,3'-(((2,2'-diselenobis(acetyl))bis(oxy))bis(3-methoxy-4,1-phenyl))diacrylic acid. The obtained crude product can be purified by conventional methods in the art, such as semi-preparative liquid chromatography, to obtain a pure product of the target compound.

[0016] Thirdly, this invention provides the application of the aforementioned organoselenium compound in the preparation of antioxidants. Compound I provided by this invention exhibits excellent antioxidant function, and its effect is significantly superior to that of organoselenium compounds with similar structures, demonstrating great potential in the field of antioxidant preparation.

[0017] Fourthly, this invention provides the use of the organoselenium compound in the preparation of medicaments for the prevention and / or treatment of diseases caused by oxidative damage. Compound I provided by this invention possesses excellent antioxidant function and is significantly more effective than organoselenium compounds with similar structures, showing great potential in the preparation of medicaments for the prevention and / or treatment of diseases caused by oxidative damage.

[0018] Fifthly, the present invention provides a food or health food with antioxidant function, which contains the organic selenide described in the present invention.

[0019] In a sixth aspect, the present invention provides a preservative comprising the organoselenide described herein.

[0020] In a seventh aspect, the present invention provides a cosmetic additive comprising the organoselenide described herein.

[0021] Compared with existing technologies, this invention combines the natural active compound sinapic acid with selenium to synthesize a novel organic selenium compound, filling the gap in the combined use of traditional Chinese medicine antioxidant active structures and selenium. This allows the antioxidant activities of the two to produce a synergistic effect, and increases their safety and antioxidant efficacy. It has great potential in the preparation of antioxidants and drugs for the prevention and / or treatment of diseases caused by oxidative damage. Attached Figure Description

[0022] Figure 1 Compound I 1 1H NMR spectrum (600MHz, DMSO-d6);

[0023] Figure 2 ESI-MS spectrum of compound I. Detailed Implementation

[0024] The following embodiments are provided to further illustrate various aspects of the invention. These embodiments are non-limiting and should not be construed as limiting any aspect of the invention. The scope of protection of the invention is limited only by the claims. Various modifications and improvements can be made to various aspects of the invention by those skilled in the art without departing from the scope of the claims, and these modifications and improvements also fall within the scope of protection of the invention.

[0025] Additionally, it should be noted that, unless otherwise specified, all materials and reagents used in the following embodiments are commonly used in the art and can be obtained through conventional commercial means; all methods used are conventional methods known to those skilled in the art.

[0026] Example: Synthesis of Compound I

[0027] Compound I is 3,3'-(((2,2'-diselenobis(acetyl))bis(oxy))bis(3,5-dimethoxy-4,1-phenyl))diacrylic acid, with the following structure:

[0028]

[0029] Compound I was synthesized using the following method:

[0030] (1) Synthesis of 2,2'-selenodiacetic acid (compound 1): 1.6 g (0.02 mol) of selenium powder was weighed and placed in a 150 mL three-necked flask. 10 mL of distilled water was added, and the mixture was stirred under nitrogen atmosphere. Then, a solution of 1.5 g (0.04 mol) of sodium borohydride dissolved in 10 mL of distilled water was slowly added dropwise. The selenium powder gradually dissolved, and the reaction solution became clear. 3.8 g (0.04 mol) of 2-chloroacetic acid was dissolved in 20 mL of distilled water, and the pH was adjusted to 9-10 with saturated sodium carbonate solution. This solution was then added to the above reaction solution, and the mixture was stirred at room temperature for 12 h. After the reaction was complete, the reaction solution was filtered. The filtrate was adjusted to pH 2-3 with dilute hydrochloric acid, concentrated to a viscous state, extracted with ethyl acetate, and the organic layers were combined. The solution was dried over anhydrous sodium sulfate, concentrated to crystallize, and then recrystallized with ethyl acetate to obtain 2.58 g of white solid, with a yield of 64.9%.

[0031] (2) Synthesis of 2,2'-selenodiacetyl chloride (compound 2): Under nitrogen protection, 0.394 g (0.002 mol) of compound 1 was dissolved in 20 mL of anhydrous tetrahydrofuran at 0 °C. 0.35 mL (0.004 mol) of a mixture of oxaloyl chloride was added dropwise to the above solution, and the reaction was continued at 40 °C for 2 h. The solvent was removed by rotary evaporation for 48 h, yielding a yellow oily substance, which is 2,2'-selenodiacetyl chloride. Note that the process should be carried out in an anhydrous and dry environment and used directly in the next step.

[0032] (3) Synthesis of Compound I: Under nitrogen protection, 0.896 g (0.004 mol) of sinapic acid was dissolved in 10 mL of anhydrous tetrahydrofuran, and 0.5 mL of pyridine was added. The mixture was pre-cooled in an ice bath. Compound 2 obtained in step (2) was dissolved in 5 mL of anhydrous tetrahydrofuran and slowly added dropwise to the pre-cooled solution. The mixture was stirred at 35 °C for 6 h. The reaction solution was evaporated to dryness under reduced pressure, dissolved in 20 mL of ethyl acetate, washed with water, and the organic phase was dried on anhydrous sodium sulfate and concentrated. The crude product was eluted with a semi-preparative liquid phase using a gradient of acetonitrile / water (volume ratio 30:70 to 100:0) to obtain purified compound I. Its structural characterization information is as follows: 1 H NMR(600MHz,DMSO-d6)δ7.57(d,J=15.9Hz,2H,2PhCH=),7.13(s,4H,2H-3,5),6.6 4(d,J=16.0Hz,2H,2=CHCOOH),3.85(s,4H,-CH2SeCH2-),3.81(s,12H,4-OCH3)(such as Figure 1 (as shown); ESI-MS(m / z): calcd for C 26 H 26 O 12 Se 609.1 [MH] - ,found 609.1 (e.g.) Figure 2(As shown) Experimental Example

[0033] Oxidative stress, caused by excess free radicals and other reactive oxygen species, is closely related to various chronic diseases such as cardiovascular disease, neurodegenerative diseases, and the aging process. DPPH and ABTS are two chemical reagents whose solution color changes after reacting with antioxidants via electron pairing; they are commonly used to evaluate the antioxidant activity of compounds. Antioxidant properties are assessed by testing a compound's ability to react with free radicals to evaluate its free radical scavenging effect.

[0034] Table 1: Radical scavenging effects of DPPH and ABTS

[0035]

[0036] As shown in Table 1, the compound I provided by this invention has EC2 activity in scavenging DPPH and ABTS free radicals. 50 The values ​​were 8.38 and 7.39 μM, respectively, significantly better than resveratrol and organoselenic compounds II and III, which have similar structures to compound I (compounds II and III are described in patent document CN 119528785 A). This demonstrates that compound I exhibits excellent antioxidant effects.

[0037] Unless otherwise stated, the technical terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. This invention may also be practiced using any methods and materials similar to or equivalent to those described herein. While specific embodiments and preferred methods and materials are described herein, they do not impose any limitation on the invention.

Claims

1. An organoselenide, characterized in that, It has the structure shown in Figure I below:

2. The method for preparing the organoselenide according to claim 1, characterized in that, It was prepared according to the following synthetic route: (1) (2) (3) 3. The preparation method according to claim 2, characterized in that, Step (1) includes: taking selenium powder, mixing it with distilled water under nitrogen protection, slowly adding sodium borohydride aqueous solution while stirring, and after the system becomes clear, adjusting the pH of 2-chloroacetic acid to 9-10 with saturated sodium carbonate solution, adding it to the above reaction solution, and stirring at room temperature; collecting the reaction solution, adjusting the pH to 2-3 with dilute hydrochloric acid, extracting with ethyl acetate, collecting the organic phase, removing water, concentrating, recrystallizing, and obtaining 2,2'-selenodiacetic acid.

4. The preparation method according to claim 2 or 3, characterized in that, Step (2) includes: dissolving 2,2'-selenodiacetic acid in anhydrous tetrahydrofuran at -5 to 5°C under nitrogen protection, adding oxaloyl chloride dropwise, and then stirring the reaction at 38 to 42°C; evaporating the solvent in the reaction solution to obtain 2,2'-selenodiacetic chloride.

5. The preparation method according to claim 2 or 3, characterized in that, Step (3) includes: preparing an anhydrous tetrahydrofuran solution of sinapic acid under nitrogen protection, adding pyridine and pre-cooling in an ice bath; slowly adding an anhydrous tetrahydrofuran solution of 2,2'-selenodiacetyl chloride, and then stirring the reaction at 33-37°C; evaporating the reaction solution to dryness, reconstituted with ethyl acetate and washed with water, extracting and collecting the organic phase, removing water, concentrating, and obtaining the crude product of 3,3'-(((2,2'-diselenodiacetyl))bis(oxy))bis(3,5-dimethoxy-4,1-phenyl))diacrylic acid.

6. The use of the compound of claim 1 in the preparation of antioxidants.

7. Use of the compound of claim 1 in the preparation of a medicament for the prevention and / or treatment of diseases caused by oxidative damage.

8. A food or health food with antioxidant function, characterized in that, It includes the organoselenide as described in claim 1.

9. A preservative, characterized in that, It includes the organoselenide as described in claim 1.

10. A cosmetic additive, characterized in that, It includes the organoselenide as described in claim 1.

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