Method for synthesizing biochanin A

Abstract

The invention relates to a method for synthesizing biochanin A, which comprises the steps of: carrying out condensation and cyclization reactions on raw materials of methoxy phenyl-acetonitril and phloroglucin, and purifying to obtain the product biochanin A. The method is characterized in that in the first condensation reaction step, isopropyl ether or n-butyl ether is used as solvent for replacing ether of the prior art, and because the boiling point of the isopropyl ether or n-butyl ether is far higher than that of the ether and does not influence the reaction effect, industrialized mass production becomes possible. In addition, anhydrous zinc chloride and chlorine hydride gas are added as catalysts in the condensation reaction, and since the anhydrous zinc chloride can greatly increase the solubility of the chlorine hydride gas, the yield of products can be enhanced by more than one time. Furthermore, crude products are purified by mixed solvent N,N- dimethylformamide-methanol, and since the dosage of the solvent is just 5-10 times of the raw materials, the production cost is greatly reduced without changing the reaction effect. The method also has the advantages of simple operation, convenient operation and the like.

Description

technical field [0001] The invention relates to a synthesis method of biochanin A suitable for industrial production, and belongs to the technical field of chemical synthesis of active molecules of anticancer drugs. technical background [0002] Flavonoids are a kind of secondary metabolites widely distributed in nature, one of the main active ingredients in medicinal plants, and have a wide range of pharmacological effects. Biochanin A (English name biochanin A, referred to as BioA) is one of the flavonoids. According to reports, biochanin A has special effects in anti-tumor and HIV virus, so it has been widely used in various related pharmaceutical products. However, since chickpein A is only micro-existed in red clover and other leguminous perennial herbs, and the growth of these herbs is limited by geographical conditions, so the number of survival is small, the growth is slow, and the drug-making cycle is long, so It is inconvenient to obtain in large quantities, so i...

AI Technical Summary

Problems solved by technology

However, limited by the reaction conditions at that time, the synthesis method had problems such as complicated synthesis routes, harsh reaction conditions, long reaction time, difficult product separation and low utilization rate of raw materials. Solvent, add hydrogen chloride gas simultaneously as catalyzer, the former is unfavorable for large-scale production because of the low boiling point, and the latter then causes yield on the low side (only 47%) because of too little solubility, and as a result, productive rate is difficult to improve, so Unable to achieve industrial production

Although a large number of scientific researchers have innovated in synthetic methods and production techniques through repeated experiments and demonstrations, they still cannot meet the requirements of industrial production, such as Wahala et al. in the document J.Chem.Soc., Perkin Trans.I 1991 , 3005-3008 mentioned that the "one-pot method" can be used to synthesize chickpein A with cheaper raw materials p-methoxyphenylacetic acid and phloroglucinol, in order to pursue the convenience of synthesis and scale up to industrial production. But in fact, this method is still limited by the first-step condensation reaction, so it is completely unfeasible. Regarding this point, Balasubramanian et al. have clearly pointed out in the document Synth.Commun.2000, 469-484

In addition, according to J.Chem.Soc., Chem.Commun.1976, 78-79 report, the ring-closing reaction of the final step in the synthetic method disclosed in this document can adopt N,N-dimethylformamide and MeSO 2 Cl synthesis of methylation reagents to complete, but the final yield of chickpein A is still low, only 66%; in addition, its purification method is to use methanol for recrystallization, but due to the need to use 60 to 150 times the amount of Methanol, so the amount used is very large, so the production cost is high

In addition, Chang et al. have also proposed (J.Agric.Food Chem.1994, 1869-1871) that microwave heating can be used to speed up the reaction in the first condensation reaction, but if this method is used in actual production, Not only the cost is too high, but also difficult to achieve in the design of the process

And some researchers also tried to start with raw materials to make a breakthrough, but did not consider the economic benefits, so the cost is too expensive, so it is difficult to reach the standard of industrial production

[0004] In short, none of the existing methods can achieve high-yield mass synthesis of chickpein A, which will undoubtedly have a great impact on the in-depth research and wide clinical application of related drugs

Images