Synthesis method of 7-dehydrocholesterol and derivatives thereof

Abstract

The invention discloses a synthesis method of 7-dehydrocholesterol and derivatives thereof, which comprises the following steps: cooling a compound (I), cuprous bromide and dimethyl sulfide compound under the protection of inert gas to obtain a reaction system, adding a Grignard reagent (II) or a Grignard reagent (III), stirring, reacting at room temperature, carrying out heating reaction, and cooling to obtain the 7-dehydrocholesterol. Performing post-treatment to obtain a product; if the product is the Grignard reagent (II), the product is 7-dehydrocholesterol and the derivative thereof; if the reagent is the Grignard reagent (III), the product is 25-hydroxy-7-dehydrocholesterol and the derivative thereof. The method is high in total yield, mild in reaction condition, simple in process route, high in product purity, low in three-waste generation amount, simple in post-treatment, environment-friendly and low in equipment requirement, the purity of 95% or above can be obtained through simple recrystallization, and conventional chemical equipment can be used for production.

Description

Technical Field

[0001] The present invention belongs to the field of chemical synthesis, and in particular relates to a method for synthesizing 7-dehydrocholesterol and its derivatives. Background Art

[0002] Currently, the main synthetic raw materials of 7-dehydrocholesterol (7-DHC) come from lanosterol, fish oil cholesterol, and other plant sterols, etc. The lanosterol and fish oil cholesterol pathways involve bromination and debromination processes, which are not environmentally friendly, or go through the path of oxidation at the 7-position, forming a hydrazone and then removing it. In the process of removing the hydrazone, strong bases such as lithium in liquid ammonia and sodium hydride need to be used. The conditions are severe, requiring low-temperature deep cooling, and it is easy to produce by-products of B-ring aromatization, making it difficult to prepare on a large scale. In addition to cholesterol raw materials from animal sources, using the fermentation products of plant sterols as raw materials conforms to the principle of natural safety, and such plant-derived raw materials are generally inexpensive. Patent CN 112608361 B uses the fermentation product of plant sterol, bisnorcholestanol BA, as the raw material to prepare 7-dehydrocholesterol in 6 steps. The first step is to introduce a leaving group at the 22-position, and the second step is to oxidize the B-ring using tetrachlorobenzoquinone. This step introduces more impurities and the post-treatment yield is low.

[0003] Patent CN 114702542 B uses bisnorcholestanol BA as the raw material and arranges the oxidative dehydrogenation of the B-ring in the first step. However, in this step, the 22-position hydroxyl group is esterified at the same time, and the ester needs to be hydrolyzed subsequently and then replaced with a leaving group, increasing the reaction steps. In the prior art, the carbonyl group or hydroxyl group at the 3-position of the A-ring is protected before alkylation, increasing the reaction steps of protection and deprotection. Summary of the Invention

[0004] In view of this, the present invention aims to propose a method for synthesizing 7-dehydrocholesterol and its derivatives to solve at least one technical problem in the background art.

[0005] To achieve the above object, the technical solution of the present invention is realized as follows: A method for synthesizing 7-dehydrocholesterol and its derivatives, comprising the following steps: Compound (I), cuprous bromide, and dimethyl sulfide complex are cooled under the protection of an inert gas to obtain a reaction system, and then a Grignard reagent (II) or a Grignard reagent (III) is added and stirred, reacted at room temperature, then heated, and the product is obtained after post-treatment; If it is a Grignard reagent (II), the product is 7-dehydrocholesterol and its derivatives; If it is a Grignard reagent (III), the product is 25-hydroxy-7-dehydrocholesterol and its derivatives; The structural formula of Compound (I) is ; The structural formula of the Grignard reagent (II) is ; The structural formula of the formatting reagent (III) is ; R 1 and R 2 are each independently selected from H, -OH, C 1-3 alkyl, =O, =C-alkyl; R 3 is H, OH, OPG; R 4 is H, OH, OPG, OC n H 2n OH, OC n H 2n OPG, n = 1 - 10; R 5 is C n H 2n LG, n = 0 - 10, and LG is a leaving group.

[0006] Furthermore, the inert gas is nitrogen; Cooling to obtain the reaction system includes cooling in an ice bath state, and the reaction system is obtained after cooling for 9 - 11 minutes.

[0007] Furthermore, the reaction time at room temperature is 2 - 2.2 h; The temperature for the heating reaction is 40 - 41 °C, and the time is 2 - 2.2 h; The post - treatment includes quenching the reaction by adding saturated ammonium chloride solution dropwise at 0 °C, then diluting with ethyl acetate and extracting twice, drying with anhydrous sodium sulfate, performing rotary evaporation under reduced pressure to obtain the crude product, and then performing recrystallization to obtain the product.

[0008] Furthermore, the preparation method of the compound (I) includes the following steps: S1: Dissolve the compound (IV) and methanol, stir and heat up, add tetrachlorobenzoquinone for a heating reaction, and obtain the compound (V) after post - treatment; S2: Dissolve the compound (V), 4 - dimethylaminopyridine, triethylamine, and dichloromethane by heating, add a dichloromethane solution of p - toluenesulfonyl chloride for reaction, and obtain the compound (VI) after post - treatment; S3: Under the protection of an inert gas, add acetic anhydride and acetyl chloride to the compound (VI), heat in the dark to reflux, cool at room temperature, perform post - treatment to obtain the compound (VII), add a mixed solution of tetrahydrofuran and methanol to the compound (VII) and stir, then add sodium borohydride for reaction, and obtain the compound (I) after post - treatment; The structural formula of the compound (IV) is ; The structural formula of the compound (V) is ; The structural formula of compound (VI) is ; The structural formula of compound (VII) is ; R is C n H 2n OH or C n H 2n OPG, n = 0~10, R 1 、R 2 are each independently selected from H, -OH, C 1-3 alkyl, =O, =C-alkyl.

[0009] R 3 is H, OH, OPG; R 4 is H, OH, OPG, OC n H 2n OH, OC n H 2n OPG, n = 1~10; R 5 is C n H 2n LG, n = 0~10, LG is a leaving group; PG is a hydroxyl protecting group.

[0010] Furthermore, the temperature for stirring and heating in step S1 is 35 - 36 °C; The time for the heating reaction in step S1 is at least 4 h; The temperature for the heating reaction in step S1 is 65 - 66 °C; The post-treatment in step S1 includes adding dichloromethane for dilution, then extracting with an aqueous KOH solution, retaining the organic phase, dissolving the product in the organic phase, drying with anhydrous sodium sulfate, rotary evaporation under reduced pressure to obtain the crude product, and then performing recrystallization to obtain compound (V).

[0011] Furthermore, the temperature for heating and dissolving in step S2 is 40 - 41 °C, and the reaction time for adding the dichloromethane solution of p-toluenesulfonyl chloride is 4 - 5 h; The post-treatment in step S2 includes naturally cooling the system to 25 - 26 °C, quenching the reaction by adding an aqueous methanol solution to the system, then adding a saturated sodium chloride aqueous solution, extracting and separating, retaining the organic phase, drying with anhydrous sodium sulfate, rotary evaporation of the organic phase under reduced pressure to obtain the crude product, and then performing recrystallization to obtain a white solid (VI).

[0012] Furthermore, the inert gas in step S3 is nitrogen; The volume of acetic anhydride in step S3 is greater than the volume of acetyl chloride; In step S3, the time for heating in the dark to the reflux reaction is 4 - 5 h, and the temperature for heating in the dark to the reflux reaction is 100 - 119 °C; The post-treatment in step S3 to obtain the crude product includes rotary evaporation at 75 - 76 °C for at least 1 h, and further concentration with an oil pump for at least 30 minutes to obtain a rice-brown crude product, and then proceed to the next reaction.

[0013] 8. A method for synthesizing 7-dehydrocholesterol and its derivatives according to claim 4, characterized in that: in step S3, the temperature for adding sodium borohydride for reaction is 0 °C, and the reaction time is 10 - 11 h; In the mixed solution of tetrahydrofuran and methanol in step S3, the mass ratio of tetrahydrofuran to methanol is 1:1; The post-treatment in step S3 includes quenching with saturated ammonium chloride solution, extracting with ethyl acetate and saturated sodium chloride solution, retaining the organic phase, drying with anhydrous sodium sulfate, rotary evaporation under reduced pressure of the organic phase to obtain the crude product, followed by recrystallization, and concentration under reduced pressure to obtain compound (I).

[0014] The synthetic route of this application is: Compared with the prior art, the method for synthesizing 7-dehydrocholesterol and its derivatives of the present invention has the following advantages: 1. This application uses the cheap and easily available plant-derived bisnorcholestanol BA as the raw material, which has a wide source and low cost, significantly reduces the production cost, and is green and environmentally friendly, meeting the concept of sustainable development; the raw material of this application has good stability and is easy to store and transport.

[0015] 2. This application has a high total yield, mild reaction conditions, a simple process route, a high total yield, high product purity, and a purity of more than 95% can be obtained through simple recrystallization. The amount of three wastes generated is small, the post-treatment is simple, it is environmentally friendly, the equipment requirements are low, and it can be produced using conventional chemical equipment. The product is easy to purify and is more suitable for industrial production.

[0016] 3. This application synthesizes the target product by a one-step method from compound (I), without involving intermediate steps, with a high total yield and high product purity, solving the problem of multi-step synthesis in the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The drawings constituting a part of the present invention are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings: Figure 1 is the hydrogen spectrum diagram of 7-dehydrocholesterol described in Example 1 of the present invention; Figure 2 is the carbon spectrum diagram of 7-dehydrocholesterol described in Example 1 of the present invention; Figure 3 1H NMR spectrum of 25-hydroxy-7-dehydrocholesterol described in Example 2 of the present invention; Figure 4 13C NMR spectrum of 25-hydroxy-7-dehydrocholesterol described in Example 2 of the present invention. Detailed implementation manners

[0018] It should be noted that, without conflict, the embodiments in the present invention and the features in the embodiments may be combined with each other.

[0019] The present invention will be described in detail below with reference to the accompanying drawings and in combination with embodiments.

[0020] The Grignard reagent (II) was purchased from Zesheng Biochemical Technology (Shanghai) Co., Ltd.

[0021] The Grignard reagent (III) was purchased from Zesheng Biochemical Technology (Shanghai) Co., Ltd.

[0022] Example 1 Synthesis of compound (b) ; At room temperature, raw material (a) (5 g, 15.1 mmol, 1 eq) was added to a 50 mL three-necked round-bottom flask, and then 30 mL of methanol was added to the flask. The mixture was stirred and heated to 35 °C. After complete dissolution, the system was light yellow. Then, tetrachlorobenzoquinone (4.8 g, 19.5 mmol, 1.3 eq) was added to the system, and the temperature was raised to 65 °C. The reaction was completed after about 4 h. Monitored by TLC, the developing agent was selected as petroleum ether: ethyl acetate = 2:1, and phosphomolybdic acid was used for color development. The raw material was completely consumed. Then, 50 mL of dichloromethane was added to the system for dilution, and then extracted with 5% KOH aqueous solution. The organic phase was retained, and the product was dissolved in the organic phase. It was dried over anhydrous sodium sulfate, and the crude product was obtained by rotary evaporation under reduced pressure and then recrystallized to obtain a yellow solid (b), weighing 4.75 g, with a purity of 96% and a yield of about 95%.

[0023] Synthesis of compound (c) ; At room temperature, compound (b) (1.7 g, 5.2 mmol, 1 eq), 4-dimethylaminopyridine (DMAP) (250 mg, 2.08 mmol, 0.4 eq), triethylamine (TEA) (1.8 mL, 18.2 mmol, 3.5 eq) and 30 mL of DCM were added to a 50 mL single-necked round-bottom flask. The temperature was raised to reflux, and the elevated temperature was 40 °C. After complete dissolution, the system was a light yellow transparent liquid. A solution of p-toluenesulfonyl chloride (TsCl) (1.58 g, 8.32 mmol, 1.6 eq) in dichloromethane (DCM) (10 mL) was added to the system using a constant pressure dropping funnel. The reaction continued under reflux, and the color of the system gradually deepened to yellow transparent. After about 4 - 5 h, TLC monitoring was carried out. The developing agent was petroleum ether:ethyl acetate = 3:1, and phosphomolybdic acid was used for color development. The reaction raw materials were completely consumed. After the reaction was completed, the system was naturally cooled to 25 °C, and 10 mL of a methanol aqueous solution (methanol:water = 1:1) was added dropwise to the system using a dropper to quench the reaction. Then 30 mL of saturated sodium chloride aqueous solution was added, and extraction and liquid separation were carried out. The organic phase was retained, dried over anhydrous sodium sulfate, and the organic phase was rotary evaporated under reduced pressure to obtain a crude product. Recrystallization from methanol gave 2.1 g of white solid compound (c) with a purity of 96% and a yield of 85%.

[0024] Synthesis of compound (e) ; At room temperature, compound (c) (900 mg, 1.9 mmol, 1.0 eq) was added to a three-necked round-bottom flask. After nitrogen protection, 5.8 mL of acetic anhydride (Ac2O) and acetyl chloride (AcCl) (1.5 mL, 19 mmol, 10.0 eq) were added. In this step, the volume of acetic anhydride was required to be greater than that of acetyl chloride. If the volumes of the two were similar or acetyl chloride was more than acetic anhydride, the double bond would shift to the other side of the same ring. The temperature was raised to reflux under light protection, and the temperature was raised to 100 °C. The color of the system gradually deepened from light yellow to brownish yellow. After about 4 - 5 h, TLC monitoring was carried out. The developing agent was petroleum ether:ethyl acetate = 3:1, and phosphomolybdic acid was used for color development. It was observed that most of the raw materials were completely consumed. The reaction solution was cooled to room temperature, transferred to a round-bottom flask, and rotary evaporated at about 75 °C for about 1 hour to remove most of the solvents - acetyl chloride and most of the acetic anhydride. The oil pump was continued to concentrate for 30 minutes to obtain a beige crude product (d), which was directly used for the next reaction without purification.

[0025] In the cold trap, after adding the crude product (d) (1 g, 1.9 mmol, 1 eq) to a 50 mL round-bottom flask, 15 mL of a mixed solution of tetrahydrofuran (THF) and methanol (CH3OH) (tetrahydrofuran:methanol = 1:1) was added. After complete stirring and dissolution, sodium borohydride (0.7 g, 10 mmol, 10 eq) was added. After reacting for about 10 h, TLC monitoring was carried out. The developing agent was petroleum ether:ethyl acetate = 3:1, and phosphomolybdic acid was used for color development. The raw materials were completely consumed. Saturated ammonium chloride solution was added to quench the reaction, and extraction was carried out with ethyl acetate and saturated sodium chloride solution. The organic phase was retained, dried over anhydrous sodium sulfate, and the organic phase was rotary evaporated under reduced pressure to obtain a crude product, which was then recrystallized. After concentration under reduced pressure, a white solid compound (e) was obtained, with a purity of 90%, weighing 0.85 g, and the total yield of the two steps was 85%.

[0026] Synthesis of T1 (7-dehydrocholesterol) ; At room temperature, cuprous bromide and dimethyl sulfide complex (88 mg, 0.4 mmol, 1.0 eq) and compound (e) (250 mg, 0.4 mmol, 1.0 eq) were added to a round-bottom flask. After nitrogen protection, it was cooled in an ice bath for 10 min. Then, an isopentylmagnesium bromide solution (10 mL of THF) (0.346 g, 2 mmol, 5 eq) was sucked into a syringe and added to the system. At the same time, stirring was started. After addition, the ice bath was removed and the system was placed at room temperature. The reaction was monitored by TLC. After 2 h, there were still raw materials remaining in the reaction. The temperature was raised to 40 °C and the reaction was continued for 2 h. The developing agent was petroleum ether:ethyl acetate = 3:1, and phosphomolybdic acid was used for color development. The reaction was placed at 0 °C and 5 mL of saturated ammonium chloride solution was slowly added dropwise with a dropper to quench the reaction. Then, it was diluted with ethyl acetate and extracted twice. The organic phases were combined, dried over anhydrous sodium sulfate, and rotary evaporated under reduced pressure to obtain a crude product, which was then recrystallized to obtain white solid 7-dehydrocholesterol, weighing 125 mg, with a purity of 98% and a yield of 81%.

[0027] 11H NMR (400 MHz, CDCl3) δ 5.57 (dd, J = 5.7, 2.5 Hz, 1H), 5.38 (dt, J= 5.6, 2.7 Hz, 1H), 3.63 (tt, J = 11.2, 4.2 Hz, 1H), 2.47 (ddd, J = 14.3,4.7, 2.3 Hz, 1H), 2.28 (tq, J = 13.9, 2.2 Hz, 1H), 2.09 (ddd, J = 12.7, 4.8,2.7 Hz, 1H), 1.89 (tdd, J = 9.8, 7.3, 4.1 Hz, 4H), 1.74 – 1.56 (m, 4H), 1.54– 1.01 (m, 14H), 0.97 – 0.91 (m, 6H), 0.86 (dd, J = 6.6, 1.9 Hz, 6H), 0.61(s, 3H).

[0028] 13 13C NMR (101 MHz, CDCl3) δ 141.6, 139.9, 119.7, 116.4, 70.6, 56.0,54.6, 46.4, 43.0, 40.9, 39.6, 39.3, 37.1, 36.3, 28.2, 28.1, 24.0, 23.2, 23.0,22.7, 21.2, 19.0, 16.4, 12.0.

[0029] Example 2 The difference from Example 1 lies in the use of Grignard reagent (Ⅲ); At room temperature, cuprous bromide and dimethyl sulfide complex (88 mg, 0.4 mmol, 1.0 eq) and compound (e) (250 mg, 0.4 mmol, 1.0 eq) were added to a round-bottom flask. After being protected by nitrogen, it was cooled in an ice bath for 10 min. Then, 3-methyl-3-(trimethylsilyloxy)butylmagnesium bromide solution (10 mL of THF) (1.05 g, 2 mmol, 5 eq) was sucked with a syringe and added to the system. At the same time, stirring was turned on. After the addition, the ice bath was removed and the reaction was placed at room temperature. The reaction was monitored by TLC. After 2 h, there was still raw material remaining. The temperature was raised to 40 °C and the reaction was continued for 2 h. The eluent was petroleum ether:ethyl acetate = 3:1. Phosphomolybdic acid was used for color development and almost no raw material remained. The reaction was quenched by slowly adding 5 mL of saturated ammonium chloride solution at 0 °C with a dropper, then diluted with ethyl acetate and extracted twice. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure by rotary evaporation to obtain the crude product, which was recrystallized to obtain 25-hydroxy-7-dehydrocholesterol, weighing 153 mg, with a purity of 98% and a yield of 96%.

[0030] 1 H NMR (400 MHz, CDCl3) δ 5.57 (dd, J = 5.8, 2.5 Hz, 1H), 5.38 (dt, J = 5.6, 2.7 Hz, 1H), 3.63 (tt, J = 11.2, 4.1 Hz, 1H), 2.47 (ddd, J = 14.4, 4.9, 2.3 Hz, 1H), 2.37 – 2.14 (m, 2H), 2.12 – 2.03 (m, 1H), 1.90 – 1.85 (m, 3H), 1.79 – 1.29 (m, 17H), 1.21 (s, 7H), 0.98 – 0.86 (m, 6H), 0.62 (s, 3H).

[0031] 13C NMR (101 MHz, CDCl3) δ 141.5, 139.9, 119.7, 116.4, 71.3, 70.6, 55.9, 54.6, 46.4, 44.5, 43.1, 40.9, 39.3, 38.5, 37.2, 36.5, 36.2, 32.1, 29.5, 29.4, 28.3, 23.2, 21.3, 20.9, 19.0, 16.4, 12.0.

[0032] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for synthesizing 7-dehydrocholesterol and its derivatives, characterized in that: The method comprises the following steps: cooling a compound (I), cuprous bromide and a dimethyl sulfide complex under the protection of an inert gas to obtain a reaction system, adding a Grignard reagent (II) or a Grignard reagent (III) and stirring, reacting at room temperature, then heating the reaction, and obtaining a product after post-treatment; If it is a Grignard reagent (II), the product is 7-dehydrocholesterol and its derivatives; If it is Grignard reagent (III), the product is 25-hydroxy-7-dehydrocholesterol and its derivatives; The structural formula of compound (I) is ; The structural formula of the Grignard reagent (II) is ; The structural formula of the Grignard reagent (III) is ; R 1 , R 2 Each independently selected from H, -OH, C 1-3 Alkyl, =O, =C-alkyl; R 3 H, OH, OPG; R 4 is H, OH, OPG, OC n H 2n OH, OC n H 2n OPG, n = 1 to 10; R 5 C n H 2n LG, n = 0~10, LG is the leaving group; PG is a hydroxyl protecting group.

2. The method for synthesizing 7-dehydrocholesterol and its derivatives according to claim 1, characterized in that: The inert gas is nitrogen; Cooling the reaction system includes cooling in an ice bath for 9-11 minutes to obtain the reaction system.

3. The method for synthesizing 7-dehydrocholesterol and its derivatives according to claim 1, characterized in that: The reaction time at room temperature is 2-2.2h; The temperature of the temperature-raising reaction is 40-41°C and the time is 2-2.2h; The post-treatment includes placing the reaction at 0°C, adding a saturated ammonium chloride solution with a dropper to quench, then adding ethyl acetate to dilute and extract twice, drying over anhydrous sodium sulfate, and vacuum rotary evaporation to obtain a crude product, which is then recrystallized to obtain the product.

4. The method for synthesizing 7-dehydrocholesterol and its derivatives according to claim 1, characterized in that: The preparation method of compound (I) comprises the following steps: S1: Compound (IV) and methanol are dissolved, stirred and heated, chlorobenzoquinone is added to react at a higher temperature, and compound (V) is obtained after post-treatment; S2: Compound (V), 4-dimethylaminopyridine, triethylamine and dichloromethane are dissolved by heating, and a dichloromethane solution of p-toluenesulfonyl chloride is added to react, and compound (VI) is obtained after post-treatment; S3: Compound (VI) is added with acetic anhydride and acetyl chloride under the protection of an inert gas, and the mixture is heated to reflux in the dark, cooled at room temperature, and post-treated to obtain compound (VII). A mixed solution of tetrahydrofuran and methanol is added to compound (VII) and stirred, and sodium borohydride is added to react, and post-treated to obtain compound (I); The structural formula of compound (IV) is ; The structural formula of compound (V) is ; The structural formula of compound (VI) is ; The structural formula of compound (VII) is ; R is C n H 2n OH or C n H 2n OPG, n = 0~10, R 1 , R 2 Each independently selected from H, -OH, C 1-3 Alkyl, =O, =C-alkyl; R 3 H, OH, OPG; R 4 is H, OH, OPG, OC n H 2n OH, OC n H 2n OPG, n = 1~10; R 5 C n H 2n LG, n = 0~10, LG is the leaving group; PG is a hydroxyl protecting group.

5. The method for synthesizing 7-dehydrocholesterol and its derivatives according to claim 4, characterized in that: The stirring and heating temperature in step S1 is 35-36°C; The temperature-raising reaction time in step S1 is at least 4 hours; The temperature of the temperature-raising reaction in step S1 is 65-66°C; The post-treatment in step S1 includes adding dichloromethane for dilution, followed by extraction with a KOH aqueous solution, retaining the organic phase, dissolving the product in the organic phase, drying over anhydrous sodium sulfate, and vacuum rotary evaporation to obtain a crude product, followed by recrystallization to obtain compound (V).

6. The method for synthesizing 7-dehydrocholesterol and its derivatives according to claim 4, characterized in that: The temperature for heating and dissolving in step S2 is 40-41°C, and the reaction time for adding the dichloromethane solution of tosyl chloride is 4-5h; The post-treatment of step S2 includes naturally cooling the system to 25-26° C., adding methanol aqueous solution to the system to quench the reaction, then adding saturated sodium chloride aqueous solution, extracting and separating the liquids, retaining the organic phase, drying over anhydrous sodium sulfate, and vacuum rotary evaporating the organic phase to obtain a crude product, which is then recrystallized to obtain a white solid (VI).

7. The method for synthesizing 7-dehydrocholesterol and its derivatives according to claim 4, characterized in that: In step S3, the inert gas is nitrogen; In step S3, the volume of acetic anhydride is greater than the volume of acetyl chloride; In step S3, the time for heating to reflux reaction in the dark is 4-5h, and the temperature for heating to reflux reaction in the dark is 100-119°C; In step S3, post-treatment is performed to obtain a crude product, including rotary evaporation at 75-76° C. for at least 1 hour, and oil pump concentration is continued for at least 30 minutes to obtain a beige crude product for the next step of reaction.

8. The method for synthesizing 7-dehydrocholesterol and its derivatives according to claim 4, characterized in that: In step S3, sodium borohydride is added to react at a temperature of 0°C and a reaction time of 10-11 hours; In step S3, the mass ratio of tetrahydrofuran to methanol in the mixed solution of tetrahydrofuran and methanol is 1:1; The post-treatment in step S3 includes adding a saturated ammonium chloride solution for quenching, extracting with ethyl acetate and a saturated sodium chloride solution, retaining the organic phase, drying over anhydrous sodium sulfate, rotary evaporating the organic phase under reduced pressure to obtain a crude product, then recrystallizing it, and concentrating under reduced pressure to obtain compound (I).

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