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7-keto cholesteryl-9-carboxyl nonane and synthesis method of fluorescent marker thereof

A technology of ketocholesterol and synthesis method, which is applied in the field of synthesis of 7-ketocholesterol-9-carboxynonane and its fluorescent markers, can solve problems such as harsh conditions, increased cost, and limited application, and achieve production The effect of low cost, less impurity content and easy operation

Active Publication Date: 2016-08-17
DALIAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] 7-ketocholesterol-9-carboxynonane (oxLig-1) is of great value as a class of active lipids, but the method disclosed in PCT / JP02 / 00723 utilizing WSC / DMAP catalyst system to chemically synthesize oxLig-1 is expensive The 7-ketocholesterol (7-KC) is a raw material, which greatly increases the cost. Therefore, it is of high scientific significance, economic and social value to develop a kind of efficient, environmentally friendly and cost-reducing synthetic method.
[0004] As mentioned above, 7-ketocholesterol-9-carboxynonane (oxLig-1) has such great scientific research and biomedical potential, but its mechanism of action is not completely clear. The main difficulty is that its molecules cannot be fluorescently labeled. Some radiolabeling techniques have harsh conditions, are prone to radioactive contamination, and have limited applications

Method used

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  • 7-keto cholesteryl-9-carboxyl nonane and synthesis method of fluorescent marker thereof
  • 7-keto cholesteryl-9-carboxyl nonane and synthesis method of fluorescent marker thereof
  • 7-keto cholesteryl-9-carboxyl nonane and synthesis method of fluorescent marker thereof

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Experimental program
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Effect test

Embodiment 1

[0035] Cholesterol and azelaic acid are used as raw materials, 1,3-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) are used as catalysts for the synthesis reaction, dichloromethane is used as a solvent, and the moles of each substance The ratio is azelaic acid: DCC: DMAP: cholesterol = 2: 1.5: 1: 1, condensed into cholesterol azelaic acid ester, the reactant is carried out in a water bath at 60°C, stirred for 12 hours, then refluxed for 12 hours, and finally filtered. The crude product was extracted and washed with saturated NaCl, the organic phase was collected, dried overnight over anhydrous sodium sulfate, and evaporated to dryness the next day for later use.

[0036]Establish an oxidation system, oxidation of the allylic position: dissolve chromic anhydride in methylene chloride, and add the reaction product and 4A molecular sieve after stirring and dissolving completely. Then use a constant pressure separatory funnel to drop TBHP with a volume fraction o...

Embodiment 2

[0047] (1) Reaction establishment (cholesterol → cholesteryl acetate): in a four-neck flask equipped with a condenser tube and a thermometer, add 15ml (0.18mol) of pyridine, 10.0g (0.023mol) of cholesterol, heat and stir; After the cholesterol was completely dissolved in pyridine, 20ml (0.21mol) of acetic anhydride was added, and the reaction was carried out at a constant temperature of 75°C for 6h, the heating was stopped, and cooled to room temperature.

[0048] (2) Post-reaction treatment: add 100ml distilled water and transfer the reactant to a separatory funnel, then extract 3 times with 40ml dichloromethane respectively, and combine the extracts; the filtrate is saturated with 1N hydrochloric acid solution and 5% sodium bicarbonate solution respectively Sodium chloride aqueous solution, washed with distilled water until neutral.

[0049] Dry over 50 g of anhydrous sodium sulfate, filter off the solid, and remove the solvent under reduced pressure.

[0050] The crude pro...

Embodiment 3

[0062] Using NBD-cholesterol and azelaic acid as raw materials, 1,3-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) as catalysts for the synthesis reaction, dichloromethane as solvent, each The molar ratio of substances is azelaic acid: DCC: DMAP: cholesterol = 2:1.5:1:1, condensed into cholesterol azelaic acid ester, the reactant is carried out in a water bath at 60°C, stirred for 12 hours, then refluxed for 12 hours, and finally filtered. The crude product was extracted and washed with saturated NaCl, the organic phase was collected, dried overnight over anhydrous sodium sulfate, and evaporated to dryness the next day for later use.

[0063] Establish an oxidation system, the oxidation of the allylic position. Chromic anhydride was dissolved in dichloromethane, and the reaction product and 4A molecular sieve were added again after stirring and dissolving completely. Then use a constant pressure separatory funnel to drop TBHP with a volume fraction of 70% i...

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Abstract

The invention relates to 7-keto cholesteryl-9-carboxyl nonane and a synthesis method of a fluorescent marker thereof. Cholesterol and azelaic acid are used as raw materials, 1,3-dicyclohexyl carbodiimide and 4-dimethylamino pyridine are used as a catalyst for synthesis reaction, and dichloromethane is used as a solvent to establish an oxidation system, and finally the 7-keto cholesteryl-9-carboxyl nonane is obtained through fat reduction reaction. The synthesis method of the 7-keto cholesteryl-9-carboxyl nonane is simple and convenient to operate, the raw materials are easy to obtain, the impurity content is low, and the production cost is low. The invention further provides a synthesis method of NBD-fluorescent group introduced 7-keto cholesteryl-9-carboxyl nonane. NBD-fluorescent groups are introduced on the basis that a basic framework structure is ensured, and finally NBD-oxLig-1 is synthesized so that the 7-keto cholesteryl-9-carboxyl nonane (oxLig-1) can produce spontaneous fluorescence and is used for tracer application in cell biology.

Description

technical field [0001] The invention relates to a synthesis method of 7-ketocholesterol-9-carboxynonane and its fluorescent marker. Background technique [0002] 7-ketocholesterol-9-carboxynonane (oxlig-1) was first isolated from oxidized low-density lipoprotein (oxLDL) by Liu Qingping et al., and was used as the specificity of serum glycoprotein β2-GPI Ligands (Liu et al., J Lipid Res 2002, 43:1486-95). With the in-depth research, it was found that oxLig-1 can activate CD36 and PPARγ signaling pathways, up-regulate the expression of ABCA1, regulate and promote the outflow of cholesterol, and inhibit the occurrence of atherosclerosis (Wenzhe Li, Dan Wang, et al: Atheroclerosis.2013, 226; 102 -109 Chi, Y, et al., J Atherosclerosis, 2014, 234(2):461-468). [0003] 7-ketocholesterol-9-carboxynonane (oxLig-1) is of great value as a class of active lipids, but the method disclosed in PCT / JP02 / 00723 utilizing WSC / DMAP catalyst system to chemically synthesize oxLig-1 is expensive...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J9/00C07J43/00C09K11/06
CPCC07J9/00C07J43/003C09K11/06C09K2211/1011C09K2211/1048
Inventor 刘庆平路遥林家彬乔辉王仁军
Owner DALIAN UNIV