Method for totally synthesizing berberrubine from catechol

Abstract

The invention relates to a method for synthesizing a drug, and concretely relates to a method for synthesizing berberrubine from catechol. The method comprises the following steps: carrying out a selective methylation reaction on the raw material catechol and 2-chloromethane to obtain o-methoxyphenol, and carrying out a selective formylation reaction to obtain 2-hydroxy-3-methoxybenzaldehyde; carrying out a methylenation reaction on catechol and 2-chloromethane to obtain piperidine, and carrying out a catalytic addition reaction on the piperidine and 2-chloroethylamine to obtain homopiperonylamine; carrying out a one-pot condensation hydrogenation reaction on the homopiperonylamine and 2-hydroxy-3-methoxybenzaldehyde under the action of a nickel-based catalyst, adding hydrochloric acid tothe obtained reaction product, cooling obtained crystals, and performing filtration to obtain a hydrochloride condensate; and refining the hydrochloride condensate, carrying out a cyclization reactionon the refined hydrochloride condensate and glyoxal under the action of a copper-based catalyst, refining the obtained reaction product, adding hydrochloric acid, performing cooling for crystallization, and filtering and washing obtained crystals to obtain the product berberrubine. The method realizes industrial total synthesis of the berberrubine, and opens up a chemical synthesis method for berberrubine drugs.

Description

technical field [0001] The invention relates to a drug synthesis method, in particular to a method for fully synthesizing berberine by using catechol as a raw material. Background technique [0002] Berberrubine (Berberrubine), also known as 9-demethylberberine, 9-demethylberberine, etc., is named for its red color. Molecular formula is C 19 h 16 NO 4 Cl, with a molecular mass of 321.33u, is a highly conjugated, electrically neutral quinone structure, dark red needle-like crystals, with a melting point of 280°C-282°C, positive for bismuth potassium iodide reaction and methylenedioxy reaction. Like berberine, it is one of the active ingredients of Coptis chinensis and other Chinese medicinal materials. It belongs to the original berberine compound and is a class of isoquinoline alkaloids. Existing research and clinical application results show that the original berberine compounds have a wide range of anti-tumor, hypoglycemic, anti-inflammatory, hypolipidemic, anti-pathog...

AI Technical Summary

Problems solved by technology

At present, the method of chemically synthesizing berberine is to obtain berberine by demethylation of berberine. The demethylation methods include heating pyrolysis method, pyridine hydrochloride melting method, urea method, and aluminum chloride catalyzed method , first esterification and then hydrolysis method, but it is not difficult to find that at present, the preparation of berbererythrine is all using berberine as raw material, which not only consumes valuable berberine medicine, but also increases the cost of medicine

[0004] Berberine itself is also an effective anti-inflammatory and antibacterial drug. Demethylating it to prepare berberine, on the one hand, consumes the output of berberine, and on the other hand, prepares berberine on the basis of berberine Alkali, the production cost continues to increase, and a small amount of research and use will not have much impact. A large number of clinical applications will inevitably cause cost increases. Full synthesis research and development, innovative

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