A kind of synthesis method of targeted antioxidant skq1 intermediate 2,3-dimethyl-p-benzoquinone

Abstract

The invention provides a method for synthesizing targeted antioxidant SKQ1 intermediate 2,3-dimethyl-p-benzoquinone, comprising the following steps: 1) 2,3-dibromo-5,6-dimethyl- P-benzoquinone was dissolved in glacial acetic acid, added reduced iron powder, stirred at room temperature for 1 hour, then heated and refluxed for 5 hours; 2) After cooling, the reaction mixture was filtered and the solvent in the filtrate was evaporated under reduced pressure, and the recovered glacial acetic acid could be Recycle and reuse, the crude product is dissolved in ethanol and adjusted to pH 9 with 5% aqueous sodium hydroxide solution, and air flow is introduced until the mixture becomes dark blue, and the reaction is completed by TLC monitoring; 3) The reaction mixture is acidified with 10% HCl To pH 4, most of the ethanol was evaporated under reduced pressure, then extracted three times with ethyl acetate, the organic phases were combined, the solvent was spin-dried to obtain an oily crude product, ethyl acetate was recovered, and the crude product was purified by silica gel flash column to obtain a pale yellow oily product. The invention synthesizes a mitochondrial antioxidant SKQ-1 intermediate, 2,3-dimethyl-p-benzoquinone; the solvent can be reused repeatedly, and the production cost is saved; it provides a raw material basis for industrialized synthesis of the mitochondrial antioxidant SKQ1.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for synthesizing 2,3-dimethyl-p-benzoquinone, an intermediate of targeted antioxidant SKQ1. Background technique [0002] In recent years, the development of new in vivo antioxidant drugs has attracted more and more attention from researchers because of their good clinical effects. Mitotech SA, a biotechnology company located in Luxembourg, has developed an innovative mitochondria-targeted antioxidant SKQ1, which has passed clinical phase II trials. Symptoms and signs. [0003] SKQ1 can help treat certain diseases of mitochondria in human cells and delay the aging of human cells. [0004] SkQ1 also selectively protects the membrane's cardiolipin from oxidation and, by doing so, prevents mitochondrial dysfunction and a cell death process called apoptosis. [0005] Russian researchers recently discovered that the antioxidant SKQ1 can effectively k...

AI Technical Summary

Problems solved by technology

[0008] At present, no company in China can carry out large-scale industrialization of SKQ1, and its synthesis scale generally only reaches the gram level, which is only suitable for research and cannot provide long-term stable commodity supply.

The synthetic route of SKQ1 reported in the literature has problems such as many by-products, difficult purification, and low yield

[0009] There are many problems in the synthesis process of the intermediate 2,3-dimethyl-p-benzoquinone required in the existing SKQ1 synthesis route. The synthesis process is complex, the yield is low, and the operation is cumbersome; concentrated sulfuric acid is used in the reaction. High-risk chemicals; production Heavy metal wastewater is produced during the process; the feeding ratio is difficult to control, resulting in increased by-products

Especially in the step where the synthetic intermediates are quinones, due to the sublimation characteristics of quinones, if the post-processing method is not appropriate, it will easily cause great losses

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