Chemical Synthesis Of Calcium Salt Of Salvianolic Acid Derivatives

Salvia miltiorrhiza Bunge is one of the most widely used traditional herbal medicines in our history,which has a history of thousands of years in clinical therapy in China.Traditional medical records of Salvia have : removing stasis and relieving pain,activating blood to promote menstruation,clearing heart fire and tranquilization.Since modern times Salvia is widely used in the treatment of coronary heart disease,myocardial infarction,blood circulation diseases,and other cardiovascular diseases.The bioactive components of S.miltiorrhiza are divided into two groups,the water-soluble phenolic acids and the lipid-soluble tanshinones.The water-soluble phenolic acids mainly contain salvianolic acid B(SAB)and salvianolic acid E(SAE).As the water-soluble phenolic acids marked pharmacological activities coupled with their ues from herbs steeped in clinical treatment.What’s more Salvianolic acid E is has much better chemical stability in water comparing than to salvianolic acid B.Therefore,in this study,Salvianolic acid E was chosen as the structural basis,which is has little content,stable chemical properties,never been studied.On the basis of its original active structure,it can be made into calcium salt.We expect new compounds with enhanced biological activity or new biological activity.The expected structure as follow:According to the structure,The synthetic route is A,B,and then reacted with calcium hydroxide.So we take Vanillin as the starting material with the hydroxylprotected,crabn chains growed,carboxyl-protected,the addition and elimination of Bromine,then 2-Bromo-3-(3,4-dimethoxy-phenyl)-acrylic acid ethyl ester is obtained;Secondly,Isovanillin by Bromine substituted,hydroxyl-protected,Miyaura,Borylation,then 3,4-dimethoxy-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-benzaldehyde is obtained.Through the Suzuki coupling reaction,carbon chain extension,ester bond elimination,the skeleton structure of salvianolic acid E is synthetized.Finally,after the removal of methoxy protection,the target compound through reaction with calcium hydroxide solution into calcium salt.