Design And Synthesis Of EED Molecular Probes And Studies On The Synthesis Of Ursodeoxycholic Acid

Malignant tumors(cancers)endanger human health and have become one of the major public health issues that seriously threatens the health of the population.Polycomb repressive complex 2(PRC2)is a multi-protein complex that catalyzes the trimethylation of lysine at position 27 on histone H3(H3K27me3).Its abnormal activity is related to the occurrence and development of cancer close relationship.The combination of H3K27me3 and EED(a β-propeller protein consisting of seven WD40repeats)stimulates the catalytic activity of PRC2 through an allosteric mechanism and is part of tumorigenesis and development.The cage pocket in EED is considered to be a pharmaceutically acceptable site,but its specific mechanism of action is unclear.To resolve this situation,EED226 based probes have been designed and synthesized,including EED-probe 01,EED-probe 02,BODIPY-tag 01,BODIPY-tag 02,Biotin-tag03,which were used to study the target and mechanisms of drugs.Ursodeoxycholic acid(UDCA)can effectively treat chronic liver diseases and gallstone diseases clinically,and is a first-line treatment drug for primary biliary cirrhosis(PBC),which has broad market prospects.However,most of the existing ursodeoxycholic acid synthesis routes use animal bile acids as starting materials.Due to bird flu,mad cow disease,etc.,there are certain safety issues.Regarding this situation,it is of great significance and industrial value to develop a safe and efficient ursodeoxycholic acid synthesis method based on plant-source materials.Two novel synthetic routes of producing ursodeoxycholic acid(UDCA)was developed through multiple reactions from cheap and commercially available bisnoralcohol(BA).The key reaction conditions,including solvents,bases and reaction temperatures of the route were investigated and optimized.Among the two routes for the synthesis of UDCA from plant-source BA,most reactions have high conversion rates,with an average yield of 91% and total yields of 59% and 57%(6 steps),respectively.Especially in the last step of reduction and hydrolysis,there are five functional groups converted with calcd97% per conversion in one-pot reaction.The novel synthetic route of ursodeoxycholic acid has potential,huge economic value,industrialization prospects and good safety.