A kind of synthetic method of targeted antioxidant skq1 intermediate 2,3-dibromo-5,6-dimethyl-p-benzoquinone

Abstract

The present invention provides a synthetic method of targeted antioxidant SKQ1 intermediate 2,3-dibromo-5,6-dimethyl-p-benzoquinone, comprising the following steps: 1) converting 2,3-dimethylphenol Dissolve in methanol, add bromine dropwise at 0°C, slowly rise to room temperature and stir for 2 hours; 2) Cool the reaction solution to 0°C, add 30% hydrogen peroxide aqueous solution dropwise, the reaction is exothermic, and the reaction temperature is controlled Below 30°C, after the dropwise addition, rise to room temperature and react overnight; 3) Drain the solvent under reduced pressure, recover methanol (it can be reused after simple drying), add ethyl acetate to dissolve the oily crude product, and dissolve it with 10% carbonic acid Washing with sodium hydrogen; 4) Drain the solvent of the crude ethyl acetate solution in step 3), the recovered ethyl acetate can be recycled, and the oily crude product is purified with a silica gel column to obtain a light green pure product powder. The present invention synthesizes a novel SKQ-1 intermediate 2,3-dibromo-5,6-dimethyl-p-benzoquinone; the solvent can be reused to save production costs; it is a new route to synthesize mitochondrial antioxidant SKQ1 Provide raw material basis.

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-dibromo-5,6-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 e...

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

Images