Total Synthesis Of Natural Product(±)-Methyl Salvianolate A

As one of the Salvianolic acid families with water-soluble extracts,natural product methyl Salvianolate A was demonstrated to have good biological activities for possessing several polyphenols.In this thesis,we designed a unique and novel total synthetic route to accomplish the total synthesis of(±)-methyl Salvianolate A.Due to the unique chemical structure of natural product(±)-methyl Salvianolate A,our work is focused on establishing ?,?-unsaturated ester structure of C7-C9.The synthetic route was commenced with o-vanillin and 4-methylpyrocatechol.After 6 steps,we established a trans-double bond of C7"-C8"via a Wittig reaction.Then,aldehyde(3)was prepared through a nucleophilic substitution after the bromine/lithium interconversion.Another fragment was started from the caffeic acid.The monohydroxyl in C8' could be obtained through classic dihydroxylation and reductive dehydroxyl.Sequentially,the monohydroxyl was reacted with phosphonoacetic acid,and the key phosphonoacetic ester intermediate was successfully established.Next,the ester proceeded via known Homer-Wadsworth-Emmons(HWE)reaction with the intermediate aldehyde(3)to establish ?,?-unsaturated ester structure of C7-C9.Finally,in the presence of HF Et3N,the TBS group was deprotected to give the free polyphenols and we successfully accomplished the total synthesis of(±)-methyl Salvianolate A.The convergent synthetic strategy in this thesis could be applied to the synthesis of other members of Salvianolic acid families or other natural products possessing similar structure.More importantly,the total synthesis of(±)-methyl Salvianolate A could supply enough source of natural compounds for the biological study and lay an important foundation for the research of Salvianolic acid families in drug development.