Synthesis And Biological Activity Study Of N-substituted Amino Acetyl Caffeic Acid Esters-derivatives

Based on the previous work,we design a novel caffeic acid ester-derivative (TM-1) choosing CAPE as lead a compound,we also intend to use various groups to substitute the phenolic hydroxyl group(TM-2),in order to investigate effects on the cytotoxic activities of different substituent groups.By retrosynthetic analysis of the target compounds,we designed a rational synthetic way.41 target compounds and intermediates have been synthesized,which have never been reported.35 of the target compounds have been tested by the cytotoxicity screenings,most of which exhibit different degrees of cytotoxic activities. Among the total,compound 2.10.6 and 2.16.6 exhibit excellent cytotoxic activities and selectivities to the tumour cell line K562,the IC₅₀ of which achieve 0.34×10^-5 mol/L and 0.10×10^-5 mol/L.In addition,the Structure-Activity Relationships(SAR) of the compounds have been discussed in order to guide our research work infuture.Besides,I engaged in the research in phytochemistry during my post-graduate stage.Based on the previous work,our investigation on the chemical constituents of the Ligularia atroviolacea(Franch.) Hand.-Mazz,has led to the isolation and identification of 4 compounds,which has been identified by the modern spectroscopic methods.This thesis is divided into 4 chapters.Chapter 1 reported the development of caffeic acid-derivatives.Chapter 2 reported the design and synthesis research of Nsubstituted amino acetyl caffeic acid ester-derivatives.Chapter 3 reported the research of the cytotoxic activities and SAR of the synthesized compounds.Chapter 4 reported the research in phytochemistry during post-graduate stage.