Method for synthesizing formoononetin

Abstract

The invention relates to a method for synthesizing formoononetin, which comprises the steps of: carrying out condensation and cyclization reaction on p-methoxyphenylacetic acid and hydroxyphenol, which are used as raw materials; and then purifying the materials to obtain the product formoononetin. The method for synthesizing formoononetin, provided by the invention is characterized in that in the first step of condensation reaction, boron triflouride-tetrahydrofuran is used for replacing boron triflouride-diethyl ether in the prior art to be used as a solvent, and because the boiling point and the safety of the tetrahydrofuran are far higher than those of the diethyl ether, the industrialized large-scale production becomes possible; and a water-methanol mixed solvent is used for product purification in the first step so as to replace a pure methanol or pure ethanol solvent in the prior part, therefore, the production cost can be obviously reduced and the effect is the same. In addition, the water-methanol mixed solvent is also used for product purification in the last step to replace the pure methanol or pure ethanol solvent in the prior part, so that the total cost can be further reduced. Moreover, the synthesizing method also has the advantages of simplicity in operation, convenience, high safety and the like.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis of active molecules of anticancer drugs, and in particular relates to a synthesis method of formononetin suitable for industrial production. Background technique [0002] Isoflavones are secondary metabolites widely distributed in nature, one of the main active ingredients in many medicinal plants, and have a wide range of pharmacological effects. Astragalus is one of the most commonly used traditional Chinese medicines. There are more than 10 species of this plant used as medicine, and the most typical one is Astragalus membranceus (English name: Astrgalus membranceus). The main active ingredient of Astragalus membranaceus (English name: Formononetin) is one of the isoflavone compounds. Formononetin has anti-cancer effect, can prevent and treat breast cancer, prostate cancer and colon cancer, and has weak estrogen effect. It can be used as a diuretic clinically and has been widely use...

AI Technical Summary

Problems solved by technology

Due to the low boiling point of ether, in industrial production, the use of boron trifluoride-ether solution is very unfavorable for large-scale safe production

Although scientific research personnel tried to innovate on other synthetic routes and production techniques through repeated experiments and demonstrations, they still could not meet the requirements of industrialized production, as recently reported by Wang et al. (Tetrahedron.Lett.2009, 50, 2121) A new synthetic route, but this route requires the use of expensive methyl triphenylphosphine bromide and Grubbs catalyst, and the overall yield is low

Another example is that Felpin et al. (Tetrahedron 2007, 63, 3010) found that the Suzuki-Miyaura reaction can be used to prepare formononetin, but this reaction also requires the use of expensive palladium catalysts, so it is not suitable for industrial production

Another example has been reported by Wahala et al. (J.Chem.Soc., Perkin Trans.I 1991, 3005) can use cheaper raw materials p-methoxyphenylacetic acid and resorcinol, and adopt "one pot method" to synthesize formonescele Florin, in order to pursue the convenience of synthesis and industrial scale-up production, but in fact this method is limited by the first condensation reaction, and it is not feasible. On this point, Balasubramanian et al. (Synth.Commun.2000, 469) clearly states that

In addition, according to the literature (J.Chem.Soc., Chem.Commun.1976, 78) reports, in the synthetic method of formononetin, the final ring-closing reaction can use N,N-dimethylformamide and MeSO 2 Cl synthetic methylation reagent is finished, but the yield of final formononetin is low (only 66%); Its purification method is to carry out recrystallization with methanol in addition, but because need use the methanol of 60~150 times of amount , so the production cost is very high

In addition, Chang et al. have also proposed (J.Agric.Food Chem.1994, 1869) that microwave heating can be used to speed up the reaction in the first step of condensation reaction, but microwave heating cannot be applied to actual industrial production at present.

In addition, researchers also tried to make breakthroughs from raw materials, but did not consider economic benefits, so the cost was too expensive, so it was difficult to meet the requirements of industrial production

[0004] In short, none of the existing synthetic methods can achieve high-yield and large-scale industrial synthesis of formonetin, which greatly affects the in-depth research and clinical application of related drugs.

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