Compound and application thereof in synthesis of oxidized resveratrol derivative

Abstract

The invention discloses a compound and application thereof in synthesis of oxidized resveratrol derivatives in the technical field of organic chemistry, according to a method, (E)-2-(2, 4-bis (benzyloxy) styryl)-4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborane and a halogenated benzene compound are sequentially subjected to a coupling reaction and a debenzylation protection reaction, and purification is performed to obtain the oxidized resveratrol derivatives. According to the present invention, by selecting different halogenated benzene compounds, a variety of oxidized resveratrol derivatives with different structures are synthesized, the individual development of the synthesis route of each product is avoided, the synthesis route of (E)-2-(2, 4-bis (benzyloxy) styryl)-4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborane is simple, the product is easily available, the structure is simple, the industrial potential is provided, and in addition, the method can be used in the field of industrial production. Through innovative reaction steps and condition optimization, further improvement of reaction selectivity and efficiency is realized in synthesis of the oxidized resveratrol derivative, meanwhile, product stability is guaranteed, the oxidized resveratrol derivative is promoted to be converted into a mainstream functional raw material, and large-scale production requirements can be met.

Description

A compound and its application in the synthesis of oxidized resveratrol derivatives Technical Field

[0001] This invention relates to the field of organic chemistry, specifically to a compound and its application in the synthesis of oxidized resveratrol derivatives. Background Technology

[0002] Oxyresveratrol, belonging to the stilbene class of compounds, has the chemical name 2,4,3′,5′-tetrahydroxystilbene and the molecular formula C2. 14 H 12 O4. Currently, it is mainly obtained through extraction and separation from mulberry twigs and Yunnan jackfruit, as well as chemical synthesis. Compared with resveratrol, oxidized resveratrol has the core advantage of stronger antioxidant, tyrosinase inhibitory, and anti-inflammatory activities, and is gradually becoming an upgraded alternative to resveratrol. To address the bottlenecks of oxidized resveratrol itself, such as poor water solubility, insufficient stability, and low bioavailability, and to expand its application scenarios and improve its efficacy, oxidized resveratrol derivatives are synthesized through structural modifications such as esterification, etherification, glycosylation, and grafting with polymers. Derivative synthesis is a key path to overcome the physicochemical and biopharmaceutics bottlenecks of oxidized resveratrol, preserving / enhancing its activity while solving application pain points, thus promoting the large-scale application of oxidized resveratrol in the pharmaceutical, cosmetic, and food industries from the laboratory.

[0003] Traditional synthetic routes for stilbene compounds are lengthy and cumbersome. Existing technologies have explored synthetic routes for stilbene compounds; for example, CN102924300B reports the preparation of corresponding stilbene compounds via decarboxylation reactions. This patent uses cuprous iodide and an o-phenanthroline-flavored catalyst, and a 2,3-diarylacrylic acid compound undergoes a microwave-assisted reaction in polyethylene glycol to purify and obtain stilbene compounds. Another example is CN106748672B, which discloses a method for preparing trans-o-hydroxydiarylethylene compounds, using isootropenes as raw materials, undergoing a ring-opening decarboxylation reaction under alkali conditions, followed by post-treatment to obtain trans-o-hydroxydiarylethylene compounds. All of these methods use a known precursor as a substrate to synthesize a final stilbene compound, and the precursors used are expensive and difficult to obtain, lacking industrialization potential. Therefore, developing simple intermediates / precursors that facilitate the synthesis of stilbene compounds has significant industrial implications. Summary of the Invention

[0004] The purpose of this invention is to provide a compound and its application in the synthesis of oxidized resveratrol derivatives in order to solve the above-mentioned technical problems.

[0005] The present invention achieves the above-mentioned objective through the following technical solution: In its first aspect, the present invention provides a compound, said compound being (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane, with the structure shown in formula (I): Formula (I) is a second aspect of the present invention, which provides a method for preparing the compound as described above, wherein (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane is synthesized from 1,3-bis(benzyloxy)benzene as a raw material by halogenation, Sonogashira cross-coupling reaction, deprotection and hydroboration reaction.

[0006] As a further optimized solution of the present invention, the specific steps include: (A-1) adding silver salt and halogen elements to an organic solvent containing 1,3-bis(benzyloxy)benzene, stirring the reaction at room temperature, concentrating and purifying the resulting product to obtain (((4-halo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl; (A-2) adding ethynyltrimethylsilane, triethylamine, palladium dichloride and cuprous iodide to an organic solvent containing ((4-halo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl, stirring the reaction at room temperature under nitrogen protection, concentrating and purifying the resulting product to obtain 2,4-bis(benzyloxy)phenylethynyltrimethylsilane; (A-3) adding silver salt and halogen elements to an organic solvent containing 2,4-bis(benzyloxy)benzene. Potassium carbonate was added to an organic solvent containing (4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl; (A-4) Copper powder and sodium methoxide were added to an organic solvent containing (4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis(1,3,2-dioxaborane); the reaction was carried out under nitrogen protection and stirred. The product was concentrated and purified to obtain (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane.

[0007] As a further optimized technical solution of the present invention, in the above preparation method, the room temperature is preferably 20-30°C, and in step (A-1), the silver salt is silver acetate or silver sulfate, preferably silver acetate, the halogen element is iodine, and the (((4-halo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl is (((4-iodo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl, wherein the 1,3-bis(benzyloxy)benzene, silver salt and halogen element are... The molar ratio is 1:1.5-2.0:1.0-1.5, the stirring time is preferably 14-18 hours, and the purification is preferably performed by silica gel column chromatography (mobile phase: petroleum ether / ethyl acetate (volume ratio) = 10 / 1); in step (A-2), the molar ratio of ((4-iodo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl to ethynyltrimethylsilane, triethylamine, bis(triphenylphosphine)palladium dichloride and cuprous iodide is 1:9-12:2-4:0.1 -0.2:0.1-0.2, the stirring time is preferably 14-18 hours, and the purification is preferably carried out by silica gel column chromatography (mobile phase: petroleum ether / ethyl acetate (volume ratio) = 30 / 1); in step (A-3), the molar ratio of 2,4-bis(benzyloxy)phenylethynyltrimethylsilane to potassium carbonate is 1:1.5-3, the stirring time is preferably 2-5 hours, and the purification is preferably carried out by silica gel column chromatography (mobile phase: petroleum ether / ethyl acetate (volume ratio) = 30 / 1); In step (A-4), the molar ratio of ((4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl, 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis(1,3,2-dioxaborane), copper powder and sodium methoxide is 1:1-2:0.1-0.2, the stirring time is preferably 14-18 hours, and the purification is preferably carried out by silica gel column chromatography (mobile phase: petroleum ether / ethyl acetate (volume ratio) = 20 / 1).

[0008] A third aspect of the present invention provides the application of the compound described above in the synthesis of oxidized resveratrol derivatives, wherein the application is as follows: using (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane as a raw material, the compound is coupled with a halobenzene compound in sequence through a coupling reaction, a debenzylation protection reaction, and purification to obtain the oxidized resveratrol derivative.

[0009] As a further optimized technical solution of the present invention, the method for synthesizing the oxidized resveratrol derivative includes the following steps: (B-1) At 20-30°C, a halobenzene compound, potassium carbonate, and diphenylphosphine-palladium dichloride are added to an organic solvent containing (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane. The mixture is heated to 90-95°C under nitrogen protection, and the reaction is stirred. The resulting product is concentrated and purified to obtain an intermediate substance. The stirring reaction time is further preferably 14-18 hours, and the purification is preferably... Silica gel column chromatography (mobile phase: petroleum ether / ethyl acetate (volume ratio) = 10 / 1); (B-2) At -75~-80℃, pentamethylbenzene and boron trichloride are added to an organic solvent containing the intermediate substance. Under nitrogen protection, the mixture is stirred at -75~-80℃. The resulting mixed reaction solution is quenched with ice water and extracted with ethyl acetate. The combined organic layers are dried with anhydrous sodium sulfate, filtered and concentrated. The residue is purified to obtain oxidized resveratrol derivatives. The preferred stirring time is 1-2 hours, and the preferred purification method is silica gel column chromatography (petroleum ether / ethyl acetate = 1-3 / 1).

[0010] As a further optimized technical solution of the present invention, the halobenzene compound is any one of 1-bromo-4-methoxybenzene, 4-bromo-1,2-dimethoxybenzene, 1-bromo-3,5-dimethoxybenzene or bromobenzene.

[0011] As a further optimized technical solution of the present invention, the oxidized resveratrol derivative is any one of (E)-(4-methoxystyryl)benzene-1,3-diol as shown in formula (II), (E)-4-(3,4-dimethoxystyryl)benzene-1,3-diol as shown in formula (III), (E)-4-(3,5-dimethoxystyryl)benzene-1,3-diol as shown in formula (IV), or (E)-(4-styryl)benzene-1,3-diol as shown in formula (V): Formula (II) Formula (III) Formulas (IV) and (V) are further optimized technical solutions of the present invention, wherein the molar ratio of (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane, halobenzene compounds, potassium carbonate and diphenylphosphine-palladium dichloride is 1:1-2:2-4:0.1-0.2.

[0012] As a further optimized technical solution of the present invention, in step (B-2), the molar ratio of the intermediate substance, pentamethylbenzene and boron trichloride is 1:9-12:1.5-3.

[0013] The "oxidized resveratrol derivative" of this invention refers to a trans-stilbene derivative containing a benzene ring modification. This trans-stilbene derivative can be represented by two benzene rings named A ring and B ring, and a vinyl group connecting the A ring and B ring. The A ring represents a benzene ring with hydroxyl substituents at positions 2 and 4, and the B ring represents a benzene ring where one or more sites at positions 3, 4, and 5 can be substituted with a methoxy group, or where positions 3, 4, and 5 are not substituted with any substituent. Preferably, the oxidized resveratrol derivative can include, but is not limited to, structures shown in formulas (II), (III), (IV), and (V).

[0014] The "intermediate substance" described in this invention refers to a trans-stilbene derivative containing a benzene ring modification. This trans-stilbene derivative can be represented by two benzene rings named A ring and B ring, and a vinyl group connecting the A ring and B ring. The A ring represents a benzene ring with benzyloxy substituents at positions 2 and 4, and the B ring represents a benzene ring where one or more sites at positions 3, 4, and 5 can be substituted with a methoxy group, or where positions 3, 4, and 5 are not substituted with any substituent. Preferably, the intermediate substance may include, but is not limited to, (E)-((4-(3,4-dimethoxystyryl)-1,3-phenylene)bis(oxy)bis(methylene))diphenyl, (E)-(((4-(4-methoxystyryl)-1,3-phenylene)bis(oxy)bis(methylene))diphenyl, and (E)-((4-(3,5-dimethoxystyryl)-1,3-phenylene)bis(oxy)bis(methylene))diphenyl.

[0015] The beneficial effects of the present invention are as follows: (1) The present invention has obtained a new compound—(E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane—through a synthetic route design. By using this compound and a halobenzene compound in sequence through coupling reaction and debenzyl protection reaction, and after purification, a variety of oxidized resveratrol derivatives with different structures were synthesized by selecting different halobenzene compounds. This avoids the need to develop a separate synthetic route for each product. Moreover, the synthetic route of the new intermediate is simple, the product is easy to obtain, and the structure is simple, which has the potential for industrialization.

[0016] (2) This invention designs a new synthetic route for oxidized resveratrol derivatives. Through innovative reaction steps and condition optimization, the reaction selectivity and efficiency in the synthesis of oxidized resveratrol derivatives are further improved, while ensuring product stability. This promotes the transformation of oxidized resveratrol derivatives into mainstream functional raw materials, which can meet the needs of large-scale production. The development of the new synthetic route for oxidized resveratrol derivatives precisely solves the key issues of raw material supply, stability, efficacy and safety in its application in the whitening and skin care field. It provides new raw material selection and technical support for the innovation of whitening and functional skin care products, and has important market significance. Attached Figure Description

[0017] Figure 1 shows the NMR spectrum of the intermediate synthesized in Example 1; Figure 2 shows the NMR H spectrum of JK-55 synthesized in Example 3; Figure 3 shows the NMR C spectrum of JK-55 synthesized in Example 3; Figure 4 shows the NMR H spectrum of JK-56 synthesized in Example 4; Figure 5 shows the NMR C spectrum of JK-56 synthesized in Example 4; Figure 6 shows the NMR H spectrum of JK-23 synthesized in Example 4; Figure 7 shows the NMR C spectrum of JK-23 synthesized in Example 4; Figure 8 shows the NMR H spectrum of JK-50 synthesized in Example 4; Figure 9 shows the NMR C spectrum of JK-50 synthesized in Example 4. Detailed Implementation

[0018] The present application will now be described in further detail with reference to the accompanying drawings. It should be noted that the following specific embodiments are only used to further illustrate the present application and should not be construed as limiting the scope of protection of the present application. Those skilled in the art can make some non-essential improvements and adjustments to the present application based on the above application content.

[0019] 1,3-Bis(benzyloxy)benzene, CAS No.: 3769-42-4; 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis(1,3,2-dioxaborane), CAS No.: 73183-34-3; 1-bromo-4-methoxybenzene, CAS No.: 104-92-7; 4-bromo-1,2-dimethoxybenzene, CAS No.: 2859-78-1; 1-bromo-3,5-dimethoxybenzene, CAS No.: 20469-65-2; bromobenzene, CAS No.: 108-86-1; Unless otherwise specified, the methods used in the following examples are conventional methods known to those skilled in the art, and the reagents and materials used are commercially available products.

[0020] Example 1 This example provides a method for synthesizing (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane (hereinafter referred to as the intermediate), including the following steps: 1.1 Synthesis of (((4-iodo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl, the synthetic route is shown in formula (1): Formula (1) was prepared by adding silver acetate (4.32 g, 25.86 mmol, 1.5 eq.) and elemental iodine (5.26 g, 20.69 mmol, 1.2 eq.) to a chloroform (100 mL) solution containing 1,3-bis(benzyloxy)benzene (5.0 g, 17.24 mmol, 1.0 eq.) at 25 °C. The resulting mixture was stirred at room temperature for 16 hours. The mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain (((4-iodo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl (6.6 g, yellow solid, yield: 92.0%). The product was analyzed by LCMS, and the LCMS value was m / z = 417.0. The synthesis of [M+H]+.1,2,2,4-bis(benzyloxy)phenylethynyltrimethylsilane is shown in the synthetic route (2). Formula (2) was prepared at 25°C by adding acetylenyltrimethylsilane (18.26 g, 186.30 mmol, 10.0 eq.), triethylamine (5.64 g, 55.89 mmol, 3.0 eq.), bis(triphenylphosphine)palladium dichloride (1.31 g, 1.86 mmol, 0.1 eq.), and cuprous iodide (353 mg, 1.86 mmol, 1.86 eq.) to a tetrahydrofuran (100 mL) solution containing (((4-iodo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl (7.75 g, 18.63 mmol, 1.0 eq.). mmol, 0.1 eq.), the resulting mixed reaction solution was stirred at room temperature for 16 hours under nitrogen protection, the resulting mixed reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30 / 1) to obtain 2,4-bis(benzyloxy)phenylethynyltrimethylsilane (7.58 g, brown solid, crude product, yield 75.6%). The product was analyzed by LCMS spectrum and it was found that LCMS: m / z = 387.2 [M+H]+.1.3, the synthesis of ((4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl, the synthetic route is shown in formula (3): Formula (3) was prepared at 25°C. Potassium carbonate (5.41 g, 39.8 mmol, 2.0 eq.) was added to a methanol / tetrahydrofuran (50 mL / 50 mL) solution containing 2,4-bis(benzyloxy)phenylethynyltrimethylsilane (7.58 g, 19.59 mmol, 1.0 eq.). The resulting mixed reaction solution was stirred at room temperature for 3 hours and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30 / 1) to obtain ((4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl (5.5 g, yellow solid, yield 89.4%); the product was analyzed by LCMS spectrum, and the LCMS: m / z = 315.1 [M+H]+.1.4. The synthesis of (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane is shown in formula (4): Formula (4) was prepared at 25°C by adding copper powder (63 mg, 0.99 mmol, 0.1 eq.) and toluene to a 50 mL ethanol solution containing ((4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl (3.1 g, 9.87 mmol, 1.0 eq.) and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis(1,3,2-dioxaborane) (3.76 g, 14.81 mmol, 1.5 eq.). Sodium alkoxide (533 mg, 9.87 mmol, 1.0 eq.) was reacted with the resulting mixture under nitrogen protection and stirred at room temperature for 16 hours. The resulting mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20 / 1) to obtain (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane (2.8 g, yellow solid, yield: 64.1%). The product was analyzed by LCMS, and the LCMS m / z was 443.2 [M+H]+. The intermediate was analyzed by nuclear magnetic resonance (NMR) (Figure 1). 1H NMR (400 MHz, DMSO-d6): δ7.58-7.54 (m, 2 H), 7.45-7.33 (m, 10 H), 6.75 (d, J=2.4 Hz 1 H), 6.63 (dd, J=8.4 Hz, 2.0 Hz, 1 H), 5.96 (d, J=18.4 Hz1 H), 5.18 (s, 2 H), 5.11 (s, 2 H), 1.21 (s, 2 H). Example 2 This example provides a method for synthesizing (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane (hereinafter referred to as the intermediate), comprising the following steps: 2.1 Synthesis of (((4-iodo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl At 20°C, silver sulfate (8.06 g, 25.86 mmol, 1.5 eq.) and elemental iodine (5.26 g, 20.69 mmol, 1.2 eq.) were added to a chloroform (100 mL) solution containing 1,3-bis(benzyloxy)benzene (5.0 g, 17.24 mmol, 1.0 eq.). The resulting mixed reaction solution was stirred at room temperature for 15 hours. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to give (((4-iodo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl (6.7 g, yellow solid, yield: 92.5%). LCMS analysis showed the product to have m / z = 417.0 [M+H]. + 2.2 Synthesis of 2,4-bis(benzyloxy)phenylethynyltrimethylsilane: At 20 °C, ethynyltrimethylsilane (18.26 g, 186.30 mmol, 10.0 eq.), triethylamine (5.64 g, 55.89 mmol, 3.0 eq.), and bis(triphenylphosphine)palladium dichloride (1.31 g, 1.86 mmol, 1.86 eq.) were added to a tetrahydrofuran (100 mL) solution containing (((4-iodo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl (7.75 g, 18.63 mmol, 1.0 eq.). 0.1 eq. of copper iodide and 353 mg of copper iodide (1.86 mmol, 0.1 eq.) were reacted in a nitrogen-protected mixture at room temperature for 16 hours. The resulting mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30 / 1) to obtain 2,4-bis(benzyloxy)phenylethynyltrimethylsilane (7.58 g, brown solid, crude product, yield 75.6%). LCMS analysis showed that the product had an LCMS value of m / z = 387.2 [M+H]. +2.3 Synthesis of ((4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl: At 20 °C, potassium carbonate (5.41 g, 39.8 mmol, 2.0 eq.) was added to a methanol / tetrahydrofuran (50 mL / 50 mL) solution containing 2,4-bis(benzyloxy)phenylethynyltrimethylsilane (7.58 g, 19.59 mmol, 1.0 eq.). The resulting mixture was stirred at room temperature for 3 hours. The mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30 / 1) to obtain ((4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl (5.5 g, yellow solid, yield: 89.4%). LCMS analysis showed that the LCMS value was m / z = 315.1 [M+H]+.

[0021] 2.4 Synthesis of (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane At 20 °C, copper powder (63 mg, 0.99 mmol, 0.1 eq.) and sodium methoxide (533 mg) were added to an ethanol (50 mL) solution containing ((4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl (3.1 g, 9.87 mmol, 1.0 eq.) and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis(1,3,2-dioxaborane) (3.76 g, 14.81 mmol, 1.5 eq.). 9.87 mmol, 1.0 eq.), the resulting mixed reaction solution was stirred at room temperature for 14 hours under nitrogen protection. The resulting mixed reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20 / 1) to obtain (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane (2.7 g, yellow solid, yield: 63.2%); referred to as the intermediate; LCMS spectrum analysis of the intermediate showed LCMS: m / z = 443.2 [M+H]+; NMR spectrum analysis of the intermediate showed: 1 H NMR (400 MHz, DMSO-d6): δ 7.58-7.54 (m, 2 H), 7.45-7.33 (m, 10 H), 6.75 (d, J=2.4 Hz 1 H), 6.63 (dd, J=8.4 Hz, 2.0 Hz, 1 H), 5.96 (d, J=18.4 Hz1 H), 5.18 (s, 2 H), 5.11 (s, 2 H), 1.21 (s, 2 H).

[0022] Example 3 uses (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane synthesized in Example 1 as a raw material. This example provides a method for synthesizing (E)-4-styrylbenzene-1,3-diol. The specific steps are as follows: 3.1 Synthesis of (E)-(((4-(4-methoxystyrene)-1,3-benzene)di(oxy))di(methylene))dibenzene. The synthetic route is shown in formula (5): Formula (5) is prepared at 25°C by adding potassium carbonate (468 mg, 3.39 mmol, 3.0 eq) and diphenylphosphine-palladium dichloride to a solution of dioxane / water (10 mL / 1 mL) containing (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane (500 mg, 1.13 mmol, 1.0 eq.) and 1-bromo-4-methoxybenzene (211 mg, 1.13 mmol, 1.0 eq.). (83 mg, 0.113 mmol, 0.1 eq), the resulting mixture was heated to 90°C and stirred for 16 hours under nitrogen protection. The resulting mixed reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain (E)-(((4-(4-methoxystyrene)-1,3-phenyl)di(oxy))di(methylene))diphenyl (380 mg, white solid, yield 79.6%). The product was analyzed by LCMS spectrum and the LCMS: m / z: 423.1 [M+H]+.3.2. Synthesis of (E)-4-(4-methoxystyrene)phenyl-1,3-diol, the synthetic route is shown in formula (6): Formula (6) was prepared by adding pentamethylbenzene (696 mg, 9.0 mmol, 10.0 eq.) and boron trichloride (1.8 mL, 1.8 mmol, 2.0 eq.) to a solution of dichloromethane (380 mg, 0.90 mmol, 1.0 eq.) containing (E)-(((4-(4-methoxystyrene)-1,3-benzene)di(oxy))di(methylene)diphenyl (1.0 M hexane solution, 1.8 mL, 1.8 mmol, 2.0 eq.) at -78 °C. The resulting mixture was stirred at -78 °C for 1 hour under nitrogen protection. The resulting reaction mixture was quenched with ice water (10 mL) and extracted with ethyl acetate (10 mL × 3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3 / 1) to obtain (E). -4-(4-methoxystyryl)benzene-1,3-diol (47.74 mg, white solid, yield: 21.9%) was named JK-55. LCMS analysis of JK-55 showed LCMS m / z: 243.0 [M+H]+. NMR analysis of JK-55 was performed (Figures 2-3). 1 H NMR (400 MHz, DMSO-d6): 7.40 (d, J=8.4 Hz, 2 H), 7.33 (d, J=9.2 Hz1 H), 7.21 (d, J=16.8 Hz, 1 H), 6.93-6.86 (m, 3 H), 6.31-6.30 (m, 2 H), 3.79(s, 3H). 13 C NMR (100 MHz, DMSO-d6): 158.8, 157.5, 155.7, 131.5, 126.8, 124.7, 121.4, 116.9, 113.6, 107.0, 102.2, 54.3. Example 4 uses (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane synthesized in Example 1 as a raw material. This example provides a method for synthesizing (E)-4-(3,4-dimethoxystyryl)benzene-1,3-diol. The specific steps are as follows: 4.1 Synthesis of (E)-((4-(3,4-dimethoxystyryl)-1,3-phenylene)bis(oxy)bis(methylene))diphenyl, the synthetic route is shown in formula (7): Formula (7) was prepared at 25°C by adding potassium carbonate (373 mg, 2.7 mmol, 3.0 eq) and diphenylphosphino-palladium dichloride (66 mg, 0.09 mmol, 0.1 eq) to a solution of dioxane / water (10 mL / 2 mL) containing (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane (400 mg, 0.9 mmol, 1.0 eq.) and 4-bromo-1,2-dimethoxybenzene (195 mg, 0.9 mmol, 1.0 eq.). The resulting mixture was heated to 90°C and stirred for 16 hours under nitrogen protection. The resulting reaction mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain (E)-((4-(3,4-dimethoxystyryl)-1,3-phenylene)bis(oxy)bis(methylene))diphenyl (258 mg, white solid, yield 63.4%). The product was analyzed by LCMS, and the LCMS m / z was 453.3 [M+H]+.4.2. The synthesis of (E)-4-(3,4-dimethoxystyryl)benzene-1,3-diol was carried out by the following route: Formula (8) was prepared by adding pentamethylbenzene (844 mg, 5.7 mmol, 10.0 eq.) and boron trichloride (1.14 mL, 1.14 mmol, 2.0 eq.) to a solution of dichloromethane (258 mg, 0.57 mmol, 1.0 eq.) containing (E)-((4-(3,4-dimethoxystyryl)-1,3-phenylene)bis(oxy)bis(methylene))diphenyl (258 mg, 0.57 mmol, 1.0 eq.) at -78 °C. The resulting mixture was stirred at -78 °C for 1 hour under nitrogen protection. The resulting reaction mixture was quenched with ice water (10 mL) and extracted with ethyl acetate (10 mL × 3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 1 / 1) to (E)-4-(3,4-dimethoxystyryl)benzene-1,3-diol (39.48 mg, white solid, yield 25.5%), named JK-56.

[0023] LCMS spectral analysis of JK-56 revealed an LCMS m / z of 273.1 [M+H]+. NMR analysis of JK-55 (Figures 4-5) further showed: 1H NMR (400 MHz, DMSO-d6): 9.56 (s, 1 H), 9.39 (s, 1H), 7.32 (d, J=8.8 Hz, 1 H), 7.14 (d, J=16.4 Hz 1 H), 7.08 (d, J=1.2 Hz 1 H), 6.98 (dd, J=8.4 Hz, 1.6 Hz, 1 H), 6.93-6.89 (m, 2 H), 6.33 (d, J=2.0 Hz 1 H), 6.24 (dd, J=8.4 Hz, 2.4 Hz, 1 H), 3.80 (s, 3 H), 3.75 (s, 3 H). 13 C NMR (100 MHz, DMSO-d6): 158.4, 156.4, 149.4, 148.4, 131.8, 127.6,124.9, 122.5, 119.2, 116.1, 112.4, 109.3, 107.6, 103.1, 55.9. Example 5 Using (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane synthesized in Example 1 as a starting material, this example provides a method for synthesizing ((E)-4-(3,5-dimethoxystyryl)benzene-1,3-diol, including the following steps: 5.1 Synthesis of (E)-((4-(3,5-dimethoxystyryl)-1,3-phenylene)bis(oxy)bis(methylene))diphenyl, the synthetic route is shown in formula (9): Formula (9) was prepared at 25°C by adding potassium carbonate (468 mg, 3.39 mmol, 3.0 eq) and diphenylphosphino-palladium dichloride (83 mg, 0.113 mmol, 0.1 eq) to a solution of dioxane / water (10 mL / 2 mL) containing (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane (500 mg, 1.13 mmol, 1.0 eq.) and 1-bromo-3,5-dimethoxybenzene (245 mg, 1.13 mmol, 1.0 eq.). The resulting mixture was heated to 90°C and stirred for 16 hours under nitrogen protection, and the resulting reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain (E)-((4-(3,5-dimethoxystyryl)-1,3-phenylene)bis(oxy)bis(methylene))diphenyl (342 mg, yellow solid, yield 66.7%). The product was analyzed by LCMS spectroscopy, and the LCMS m / z was 453.3 [M+H]+.5.2. The synthesis of (E)-4-(3,5-dimethoxystyryl)benzene-1,3-diol was carried out by the following synthetic route as shown in formula (10): Formula (10) was prepared by adding pentamethylbenzene (1.11 g, 7.5 mmol, 10.0 eq.) and boron trichloride (1.5 mL, 1.50 mmol, 2.0 eq.) to a solution of dichloromethane (342 mg, 0.75 mmol, 1.0 eq.) containing (E)-(((4-(3,5-dimethoxystyryl)-1,3-phenylene)bis(oxy))bis(methylene))diphenyl (342 mg, 0.75 mmol, 1.0 eq.) in 10 mL of 4-chloromethane solution at -78 °C. The resulting mixture was stirred at -78 °C for 1 hour under nitrogen protection. The resulting mixed reaction solution was quenched with ice water (30 mL), extracted with ethyl acetate (10 mL × 2), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 1 / 1) to ((E)-4-(3,5-dimethoxystyryl)benzene-1,3-diol (18.37 mg, white solid, yield 8.9%), named JK-23.

[0024] LCMS spectrum analysis of JK-23 showed an LCMS m / z of 273.0 [M+H]+. Nuclear magnetic resonance (NMR) analysis of JK-23 was then performed (Figures 6-7). 1H NMR (400 MHz, DMSO-d6): δ 9.61 (s, 1 H), 9.43 (s, 1 H), 7.34 (d, J=8.8 Hz, 1 H), 7.26 (d, J=16.4 Hz, 1 H), 6.92 (d, J=16.4 Hz, 1 H), 6.63 (d, J=2.4 Hz, 2 H), 6.34 (dd, J=5.2 Hz, 2.0 Hz, 2 H), 6.25 (dd, J=8.4 Hz, 2.0 Hz, 1 H), 3.76 (s, 6 H). 13 C NMR (100 MHz, DMSO-d6): δ 161.1, 158.8, 156.7, 140.9, 128.1, 124.99, 124.96, 115.6, 107.8, 104.2, 103.1, 99.4, 55.6. Example 6 uses (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane synthesized in Example 2 as a raw material. This example provides a method for synthesizing (E)-(4-styryl)benzene-1,3-diol, including the following steps: Step S1, synthesis of (E)-(((4-phenyl-1,3-phenyl)di(oxy))di(methyl))dibenzene, the synthetic route is shown in formula (11): Formula (11) was prepared at 25°C by adding potassium carbonate (282 mg, 2.04 mmol, 3.0 eq) and diphenylphosphino-palladium dichloride (49 mg, 0.068 mmol, 0.1 eq) to a solution of dioxane / water (10 mL / 2 mL) containing (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane (300 mg, 0.68 mmol, 1.0 eq) and bromobenzene (160 mg, 1.02 mmol, 1.5 eq.). The resulting mixture was heated to 90°C and stirred for 4 hours under nitrogen protection. The resulting mixed reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain (E)-(((4-phenyl-1,3-phenyl)di(oxy))di(methyl))diphenyl (186 mg, white solid, yield 69.8%). Nuclear magnetic resonance (NMR) analysis of (E)-(((4-phenyl-1,3-phenyl)di(oxy))di(methyl))diphenyl yielded the following results: 1¹H NMR (400 MHz, DMSO-d6): δ 7.58 (d, J=8.4, 1 H), 7.51-7.32 (m, 15H), 7.24-7.20 (m, 1 H), 7.14 (d, J=16.4 Hz, 1 H), 6.81 (d, J=2.0 Hz, 1 H), 6.67 (dd, J=8.4 Hz, 2.0 Hz, 1 H), 5.21 (s, 2 H), 5.13 (s, 2 H). Step S2, the synthesis of (E)-(4-styryl)benzene-1,3-diol, is shown in formula (12): Formula (12) was prepared by adding pentamethylbenzene (696 mg, 4.70 mmol, 10.0 eq.) and boron trichloride (1.0 M hexane solution, 0.94 mL, 0.94 mmol, 2.0 eq.) to a solution of dichloromethane (10 mL) containing (E)-(((4-phenyl-1,3-phenyl)di(oxy))di(methyl))diphenyl (186 mg, 0.47 mmol, 1.0 eq.) at -78 °C. The resulting mixture... The mixture was stirred at -78°C for 1 hour under nitrogen protection. The resulting mixture was quenched with ice water (10 mL) and extracted with ethyl acetate (10 mL × 3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3 / 1) to obtain (E)-(4-styryl)benzene-1,3-diol (21.26 mg, white solid, yield: 21.3%), which was named JK-50.

[0025] LCMS spectral analysis of JK-50 revealed the following: LCMS: m / z: 213.0 [M+H] + Nuclear magnetic resonance (NMR) spectroscopy analysis of JK-50 (Figures 8-9): 1 H NMR (400 MHz, DMSO-d6): δ 9.60 (s, 1 H), 9.41 (s, 1 H), 7.47 (d, J=7.6, 2 H), 7.37-7.27 (m, 4 H), 7.20-7.17 (m, 1 H), 6.98 (d, J=16.4 Hz, 1 H), 6.33 (d, J=2.4 Hz, 1 H), 6.25 (dd, J=8.4 Hz, 2.0 Hz, 1 H). 13C NMR (100 MHz, DMSO-d6): δ 158.7, 156.7, 138.8, 129.1, 127.9, 127.0, 126.2, 124.8, 124.4, 115.8, 107.7, 103.1. The above embodiments merely illustrate several implementations of the present invention, and their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make several modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

1. A compound, characterized in that, The compound is (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane, with the structure shown in formula (I): Equation (Ⅰ).

2. A method for preparing the compound as described in claim 1, characterized in that, (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane was synthesized from 1,3-bis(benzyloxy)styryl as a raw material via halogenation, Sonogashira cross-coupling reaction, deprotection, and hydroboration.

3. The method for preparing the compound according to claim 2, characterized in that, Specifically, the following steps are included: (A-1) Add silver salt and halogen element to an organic solvent containing 1,3-bis(benzyloxy)benzene, stir at room temperature, concentrate and purify the product to obtain (((4-halo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl; (A-2) Add ethynyltrimethylsilane, triethylamine, bis(triphenylphosphine)palladium dichloride and cuprous iodide to an organic solvent containing ((4-halo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl, stir at room temperature under nitrogen protection, concentrate and purify the product to obtain 2,4-bis(benzyloxy)phenylethynyltrimethylsilane; (A-3) Add 2,4-bis(benzyloxy)phenylethynyltrimethylsilane to an organic solvent containing 2,4-bis(benzyloxy)phenylethynyltrimethylsilane. Potassium carbonate was added to an organic solvent containing silane, and the mixture was stirred at room temperature. The resulting product was concentrated and purified to obtain ((4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl; (A-4) Copper powder and sodium methoxide were added to an organic solvent containing ((4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis(1,3,2-dioxaborane), and the mixture was stirred under nitrogen protection. The resulting product was concentrated and purified to obtain (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane.

4. The method for preparing the compound according to claim 3, characterized in that, In step (A-1), the silver salt is silver acetate or silver sulfate, the halogen is iodine, and the (((4-halo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl is (((4-iodo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl, with a molar ratio of 1,3-bis(benzyloxy)benzene, silver salt, and halogen being 1:1.5-2.0:1.0-1.5; in step (A-2), the ((4-iodo-1,3-phenylene)bis(oxy))bis(methylene))diphenyl reacts with ethynyltrimethylsilane, triethylamine, and di(triphenylphosphine)dichloro... The molar ratio of palladium iodide to cuprous iodide is 1:9-12:2-4:0.1-0.2:0.1-0.2; in step (A-3), the molar ratio of 2,4-bis(benzyloxy)phenylethynyltrimethylsilane to potassium carbonate is 1:1.5-3; in step (A-4), the molar ratio of ((4-ethynyl-1,3-phenylene)bis(oxy)bis(methylene))diphenyl, 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis(1,3,2-dioxaborane), copper powder, and sodium methoxide is 1:1-2:0.1-0.

2.

5. The application of the compound as described in claim 1 in the synthesis of oxidized resveratrol derivatives, characterized in that, The application is as follows: using (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane as a raw material, it is coupled with a halobenzene compound in sequence through coupling reaction and debenzylation protection reaction, and then purified to obtain the oxidized resveratrol derivative.

6. The application according to claim 5, characterized in that, The method for synthesizing the oxidized resveratrol derivative includes the following steps: (B-1) Adding a halobenzene compound, potassium carbonate, and diphenylphosphine-palladium dichloride to an organic solvent containing (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane, heating to 90-95°C under nitrogen protection, stirring the reaction, concentrating and purifying the obtained product to obtain an intermediate substance; (B-2) Adding pentamethylbenzene and boron trichloride to an organic solvent containing the intermediate substance at -75~-80°C, stirring the reaction under nitrogen protection, concentrating and purifying the obtained product to obtain the oxidized resveratrol derivative.

7. The application according to claim 5, characterized in that, The halogenated benzene compound is any one of 1-bromo-4-methoxybenzene, 4-bromo-1,2-dimethoxybenzene, 1-bromo-3,5-dimethoxybenzene, or bromobenzene.

8. The application according to claim 7, characterized in that, The oxidized resveratrol derivative is any one of (E)-4-(4-methoxystyryl)benzene-1,3-diol as shown in formula (II), (E)-4-(3,4-dimethoxystyryl)benzene-1,3-diol as shown in formula (III), (E)-4-(3,5-dimethoxystyryl)benzene-1,3-diol as shown in formula (IV), or (E)-(4-styryl)benzene-1,3-diol as shown in formula (V). Formula (II) Formula (III) Equation (Ⅳ) Formula (V).

9. The application according to claim 5, characterized in that, In step (B-1), the molar ratio of (E)-2-(2,4-bis(benzyloxy)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane, halobenzene compounds, potassium carbonate, and diphenylphosphine-palladium dichloride is 1:1-2:2-4:0.1-0.

2.

10. The application according to claim 6, characterized in that: In step (B-2), the molar ratio of the intermediate substance, pentamethylbenzene and boron trichloride is 1:9-12:1.5-3.

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