Separative Preparation And Confirmation Of The Absolute Configuration Of Several Unkown Compounds In Salvianolic Acids For Injection

Salvianolic acidsfor injection(SAFI)is the major product of Tianjin Tasly Pride Pharmaceutical Co.,LTD.in treating cardiovascular and cerebrovascular diseases.SAFI is used for blood-stasis obstruction of main and collateral channals recovery in stroke in the clinical.For the improvement of the quality control of SAFI and the Investigational New Drug Application(IND)in the European Union and FDA,we should do further research of the material basis about SAFI.Until now,we have built the fingerprint of SAFI and identified the major chromatographic peaks.Among all peaks in the fingerprint,seven compounds were identified clearly and a compound was confirmed basically,besides,planar structures of three compounds(peak 7,peak 11,peak 16)were determined.In this study,these three compounds were separated and purified to get the three monomeric compounds respectively.To determinating the absolute configurations of the three compounds,we used the methods of chiral and non-chiral chromatographic study,NMR Mosher and circular dichroism,moreover,compared the three compounds with the same planar-structure compounds that absolute configurations were confirmed as well as the fragments after acid-base hydrolysis of the three compounds.In conclusion,peak 7 was confirmed to be(7’S,8’R,8"R)-epi-lithospermic acid(Monardic Acid C),peak 11 was confirmed to be(8"R,8’"R)-salvianolic acid E(Salvianolic acid E),peak 16 was confirmed to be(7’R,8’R,8"R,8"’R)-epi-salvianolic acid B(Monardic Acid B).Although the three compounds above have been reported in the literature,peak 7 and peak 16 were separated from salvia miltiorrhiza for the first time.Determination of the absolute configurations of the compounds may contribute to a better understanding about the conversion of salvianolic acids and the material foundation of salvia miltiorrhiza and SAFI.With the research idea and practical experience of this study,a research platform was established about salvianolic acids,which provides technical support for the material foundation and quality control of salvia miltiorrhiza and its preparations.