A method for photoelectric-promoted synthesis of 7-carbonyl cholesterol

Abstract

This invention relates to the field of synthetic chemistry, specifically disclosing a method for photoelectrochemically promoted synthesis of 7-carbonyl cholesterol. The method comprises the following steps: using cholesterol as a raw material, adding N-hydroxyphthalimide, an electrolyte, and a polar solvent to form a reaction system; irradiating the reaction system with light and applying an electric current to induce an oxidation reaction in the cholesterol; and after the reaction, separating and purifying the product by silica gel column chromatography to obtain 7-carbonyl cholesterol. This invention directly utilizes carbocation radicals generated online under photo / electrochemical promotion, which can directly generate 7-carbonyl cholesterol with singlet oxygen, reducing the generation of byproducts and eliminating the need for repeated purification operations. This allows for convenient and efficient production of pure 7-carbonyl cholesterol, significantly reducing synthesis costs and improving synthesis efficiency.

Description

Technical Field

[0001] This invention relates to the field of synthetic chemistry, and more particularly to a method for photoelectric-promoted synthesis of 7-carbonyl cholesterol. Background Technology

[0002] 7-Carbonyl cholesterol is considered one of the cholesterol metabolites caused by oxidative stress or free radical damage. In vivo, it may exert toxic effects on cells through various mechanisms, including damaging cell membranes, activating immune responses, and inducing inflammation. 7-Carbonyl cholesterol may play a key role in the development of atherosclerosis. Studies have shown that 7-Carbonyl cholesterol can promote macrophage activation, inflammatory responses, and lipid deposition, leading to vascular endothelial damage. In the nervous system, 7-Carbonyl cholesterol is believed to be associated with the development of neurodegenerative diseases such as Alzheimer's disease. It may participate in the degenerative changes of the nervous system by causing oxidative damage to nerve cells, inflammatory responses, and abnormal neurotransmission.

[0003] Currently, the main methods for synthesizing 7-carbonyl cholesterol are enzymatic reactions or the action of other oxidants. However, these reaction processes often involve strong oxidants and poor selectivity, which may produce additional cholesterol oxides and require multiple purification steps. Excessive operations make it difficult to control the oxidation yield and purity of the product. Summary of the Invention

[0004] In view of the shortcomings of the prior art, the purpose of this invention is to provide a method for photoelectric-promoted synthesis of 7-carbonyl cholesterol.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows:

[0006] A method for photoelectric-promoted synthesis of 7-carbonyl cholesterol includes the following steps: using cholesterol as a raw material, N-hydroxyphthalimide as an electron transfer carrier, and adding electrolytes and polar solvents to form a reaction system, applying current and light to the reaction system, allowing cholesterol to undergo an oxidation reaction with air under photoelectric conditions, and after the reaction is completed, separating and purifying by silica gel column chromatography to obtain 7-carbonyl cholesterol.

[0007] Furthermore, the electrolyte is tetrabutylammonium chloride and / or tetrabutylammonium bromide, and the concentration of the electrolyte in the system is 0.01 to 0.05 mmol / mL.

[0008] Furthermore, the ratio of cholesterol to N-hydroxyphthalimide is: 0.09 mmol of N-hydroxyphthalimide is added for every 0.3 mmol of cholesterol.

[0009] Furthermore, the polar solvent is one or more of acetonitrile, N,N-dimethylformamide, dichloromethane, and acetone, and the ratio of the polar solvent to cholesterol is: 5-10 mL of reaction solvent is added for every 0.3 mmol of cholesterol, that is, the concentration range of cholesterol in the polar solvent is 0.03 mmol to 0.06 mmol / mL.

[0010] Furthermore, a constant current of 5–20 mA, an illumination wavelength of 370 nm, and an oxidation reaction time of 5–10 h are used. An appropriate constant current is employed to avoid the current being too small, which would prevent the voltage from reaching the redox potential of the compound, and to avoid the current being too large, which would lead to over-oxidation of the compound.

[0011] Furthermore, during the oxidation reaction, nuclear magnetic resonance spectroscopy and mass spectrometry were used to monitor the reaction progress. The reaction ended when cholesterol was completely consumed.

[0012] Furthermore, the electrode materials used in the oxidation reaction are a carbon electrode and a platinum electrode, with the carbon electrode serving as the anode and the platinum electrode serving as the cathode.

[0013] Furthermore, the carbon electrode is one of carbon cloth, carbon felt, carbon plate, and carbon rod, and the platinum electrode is a platinum sheet.

[0014] Furthermore, after the oxidation reaction is complete, the polar solvent is evaporated under vacuum, and then 7-carbonyl cholesterol is purified by silica gel column chromatography. After evaporating the eluent under vacuum, pure 7-carbonyl cholesterol is obtained.

[0015] Furthermore, the silica gel used in the silica gel column chromatography is 200-300 mesh, and the eluent is a mixture of petroleum ether and ethyl acetate, with a volume ratio of petroleum ether to ethyl acetate of 10-1:1.

[0016] The beneficial effects of this invention are as follows: This invention directly uses carbocation radicals generated online under photo / electrochemical promotion, which can directly generate 7-carbonyl cholesterol with singlet oxygen, reducing the generation of byproducts, eliminating the need for repeated purification operations, and easily obtaining pure 7-carbonyl cholesterol, reducing the risk of yield decline, greatly reducing synthesis costs, and improving synthesis efficiency; moreover, the reactants are inexpensive and readily available, the reaction process is simple and controllable, easy to operate, low in cost, and easy to scale up for synthesis. Attached Figure Description

[0017] Figure 1 Synthetic route of 7-carbonyl cholesterol under photoelectric conditions;

[0018] Figure 2 The carbon NMR spectrum of 7-carbonyl cholesterol;

[0019] Figure 3 It is 7-carbonyl cholesterol [M+H]+ High-resolution mass spectrum. Detailed Implementation

[0020] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention are within the protection scope of the present invention.

[0021] Example 1

[0022] A method for photoelectric-promoted synthesis of 7-carbonyl cholesterol, Figure 1 The synthetic route is shown below, and the specific method is as follows:

[0023] Cholesterol (116 mg, 0.3 mmol), N-hydroxyphthalimide (14.7 mg, 0.09 mmol), and the electrolyte tetrabutylammonium chloride (83 mg, 0.3 mmol) were added to a three-necked reaction tube. A stir bar was added, and a 1 cm*1 cm*0.3 mm carbon cloth electrode and a platinum sheet electrode were fixed to a #24 rubber stopper using electrode clamps, serving as the anode and cathode of the reaction, respectively. These were then fixed to the three-necked reaction tube, and all three ports of the tube were sealed with rubber stoppers. Next, 1 mL of dichloromethane and 5 mL of acetone were added to the three-necked reaction tube as reaction solvents, and the reaction was carried out under a constant current of 10 mA and 370 nm illumination for 5 h. After the reaction, the solvent was evaporated under vacuum, and 7-carbonyl cholesterol was purified by silica gel column chromatography with a mesh size of 200-300. The eluent was a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1. The product 7-carbonyl cholesterol was obtained by evaporating the solvent under vacuum. Theoretically, the yield of 7-carbonyl cholesterol is 120 mg, but the actual yield was 84 mg, with a yield of 70% and a purity of >98% (NMR).

[0024] Comparative Example

[0025] The oxidizing agent method for synthesizing 7-carbonyl cholesterol by tert-butyl peroxide oxidation is as follows:

[0026] Cholesterol (116 mg, 0.3 mmol), 70% tert-butyl hydrogen peroxide aqueous solution (1.37 mL, 10 mmol), dichloromethane (1 mL), and acetone (5 mL) were added to a 10 mL round-bottom flask. A stir bar was added, the flask was sealed with a rubber stopper, and the atmosphere was replaced with nitrogen. The reaction was carried out at 50 °C for 12 h. After the reaction, the solvent was evaporated under vacuum, and 7-carbonyl cholesterol was purified by silica gel column chromatography (200–300 mesh) using a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1. The product 7-carbonyl cholesterol was obtained by evaporating the solvent under vacuum. Theoretically, the yield of 7-carbonyl cholesterol was 120 mg, but the actual yield was 9 mg, with a yield of 7.5% and a purity >98% (NMR).

[0027] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for photoelectric-promoted synthesis of 7-carbonyl cholesterol, characterized in that, The steps are as follows: Using cholesterol as a raw material, N-hydroxyphthalimide, electrolyte, and polar solvent are added to form a reaction system. The reaction system is irradiated with light and an electric current is applied to allow the cholesterol to undergo an oxidation reaction. After the reaction is completed, 7-carbonyl cholesterol is obtained by separation and purification by silica gel column chromatography. The electrolyte is tetrabutylammonium chloride and / or tetrabutylammonium bromide, and the concentration of the electrolyte in the system is 0.01-0.05 mmol / mL. The polar solvent is one or more of acetonitrile, N,N-dimethylformamide, dichloromethane, and acetone. The ratio of the polar solvent to cholesterol is 5-10 mL of reaction solvent per 0.3 mmol of cholesterol. The current is a constant current of 5-20 mA, the light wavelength is 370 nm, and the oxidation reaction time is 5-10 h.

2. The method for photoelectric-promoted synthesis of 7-carbonyl cholesterol according to claim 1, characterized in that, The ratio of cholesterol to N-hydroxyphthalimide is: 0.09 mmol of N-hydroxyphthalimide for every 0.3 mmol of cholesterol.

3. The method for photoelectric-promoted synthesis of 7-carbonyl cholesterol according to claim 1, characterized in that, During the oxidation reaction, nuclear magnetic resonance spectroscopy and mass spectrometry were used to monitor the reaction progress. The reaction ended when cholesterol was completely consumed.

4. The method for photoelectric-promoted synthesis of 7-carbonyl cholesterol according to claim 1, characterized in that, The electrode materials used in the oxidation reaction are a carbon electrode and a platinum electrode, with the carbon electrode serving as the anode and the platinum electrode serving as the cathode.

5. The method for photoelectric-promoted synthesis of 7-carbonyl cholesterol according to claim 4, characterized in that, The carbon electrode is one of carbon cloth, carbon felt, carbon plate, and carbon rod, and the platinum electrode is a platinum sheet.

6. The method for photoelectric-promoted synthesis of 7-carbonyl cholesterol according to claim 1, characterized in that, After the oxidation reaction was completed, the polar solvent was evaporated under vacuum, and then 7-carbonyl cholesterol was purified by silica gel column chromatography. After evaporating the eluent under vacuum, pure 7-carbonyl cholesterol was obtained.

7. The method for photoelectric-promoted synthesis of 7-carbonyl cholesterol according to claim 1, characterized in that, The silica gel used in the silica gel column chromatography is 200-300 mesh, and the eluent is a mixture of petroleum ether and ethyl acetate, with a volume ratio of petroleum ether to ethyl acetate of 10-1:1.

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