Total Synthesis Of1,5-O-Dicaffeoylquinic Acid (IBE-5)

Dicaffeoylquinic acid(DCQAs), a new kind of natural compound with anti-viruseffects, was always respected by the medical workers. Recently, DCQAs and the esterderivatives were found to have great inhinition on the HBV antigen presentation andDNA replication.1,5-O-dicaffeoylquinic acid(IBE-5)was a very important composition extractedfrom coffee bean or Inula flower and was the first proprietary intellectual propertyrights medicine which showed anti-HBV and HIV simultaneously. IBE-5havesuccessfully completed the phase I and IIa clinical trials on anti-HBV. Scholarsshowed great respect on IBE-5, but mostly concentrated in the plant sources andpharmacological studys. Research on the chemical synthesis of IBE-5was rarely andthe total yield was low.Our paper focused on the total synthesis of IBE-5and three synthetic routs havebeen tried. The first one was the methyl ester rout but was given up due to theunsuccessfully of selectively hydrolyze1,5-O-dicaffeoylquinic acid methyl ester. Thesecond one was allyl ester rout, which was also given up due to the hydrolyze step.The last rout was similar to the methyl ester rout, but used the sodium salt of quinicacid as the starting material instead of quinic methyl ester. And we explored the bestcondition for the esterification of sodium salt3,4-O-isopropylidene quinate. Thereaction of rout III was uncomplicated with high yields of every steps, and the targetcompound was preliminary validated by1H NMR、LC/MS and other methods.