Synthetic And Bioactivity Of Studies Salvianolic Acid A Derivatives

Danshen,also known as Red ginseng,is commonly used in Chinese medicine.The active ingredients in Danshen can be divided into two parts: lipophilic and hydrophilic compounds.Most hydrophilic compounds components are phenolic acid compounds,salvianolic acid A is one of the main components of phenolic acid compounds.The synthesis and biological activities of salvianolic acid A derivatives were studied in this paper.In the first part of the thesis,a general method was used to synthesize salvianolic acid A small molecular probe and a series of salvianolic acid A derivatives.1)The synthesis of α-β-unsaturated carboxylic acid fragments was completed by Heck coupling reaction and Knoevenagel condensation reaction.Salvianolic acid A small molecular probe was prepared by condensation with R-hydroxyl fragment or R-amine substrate fragment and removal of protective group.2)Twelve salvianolic acid derivatives were synthesized by preserving the ester group in salvianolic acid A,modifying the A,B and C rings of salvianolic acid A through oxidation state modification and changing the ester bond in salvianolic acid A into an amide bond.In collaboration with the research group of Luo Cheng,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,the activity of salvianolic acid A and its derivatives was tested based on Alpha Screen method,and the structure-activity relationship of salvianolic acid A was preliminatively established.In the second part of the paper,the low bioavailability of salvianolic acid A was solved by using prodrug modification strategy.Three salvianolic acid A carbonate prodrugs were synthesized by four steps chemical conversion using allyl group as hydroxyl group with yield of 35%-45%.