New Process For Synthesis Of Natural Phytoestrogen Polyhydroxyisoflavone

With a wide pharmacological activity,Natural phytoestrogen isoflavones can effectively prevent and treat various diseases,such as cardiovascular diseases,improving the immune system,anti-cancer,anti-inflammation and so on.It is limited to extract isoflavones from natural plant.Therefore,chemists and pharmacologists pay more attention to the chemical synthesis of isoflavones.On the basis of summarizing the synthetic methods of isoflavones,synthetic route was designed to synthesize 3',4',7-trihydroxy isoflavone(3',4',7-THIF)and 3',4',5,7-tetrahydroxy isoflavone(3',4',5,7-THIF)in this article.Six steps were included in the synthetic route,such as hydrolysis,acylation,Friedel-Crafts acylation,selective demethylation,cyclization and demethylation.In addition,the process conditions were studied and optimized.Firstly,"one-pot" process was put forward to synthesize the key intermediate 2-hydroxy-3',4,4',6-trimethoxy deoxybenzoin(HTrMDB)and 2-hydroxy-3',4,4',6-tetramethoxydeoxybenzoin(HTeMDB)in this paper.The reactions of F-C acylation and selective demethylation were carried out in one pot without separation of intermediate products.The"One-pot" reaction is easy to operate,simple post-processing and greatly reduce the amount of solvent and catalyst,lower cost and so on.Secondly,cheap materials such 3,4-dimethoxy phenylacetonitrile(DMBAN)and 1,3-Dimethoxy benzene(DMB)were used as raw materials to synthesize 3',4',7-THIF.As a key intermediate of isoflavone,HTrMDB was obtained by sub-step and "one pot" process respectively.The results showed that the "one pot" process was more preferred.The purity of the crude product was 89.71%and the yield was 77.02%.After recrystallization the purity could be reached as high as 99.16%.And then the sub-step reaction was optimized through orthogonal regression experiments.After amplification experiments,the better conditions were proved to be stable and reliable.For the cyclization,triethyl orthoformate was used as the carbon reagent and morpholine as a catalyst.The purity of the crude product was 99.01%,and the yield was 90.40%.This product could be used as raw materials for the next step without recrystallization.With 40%hydrobromic acid,all methyl of the 3',4',7-trimethoxy isoflavone could be removed to obtain 3',4',7-THIF in one time with 96.14%purity and 83.98%yield.The total yield of the 3',4',7-THIF was 56.34%.Thirdly,based on investigation of the pocess conditions of 3',4',7-THIF,3',4',5,7-THIF was successfully synthesized with DMBAN and 1,3,5-trimethoxy(TMB)as raw materials.Total yield was 57.25%.The better conditions were received by optimizing of process.In short,the route of "one-pot" process has the advantages that raw materials are easy to get,and the route is simple,easy operation,mild reaction conditions,no complex post-process and so on.Compared with other synthesis methods,the process we provided is more suitable for industrial production.All of the structures of products were characterized by H-NMRand MS.