Studies On Total Synthesis Of Natural Product Dihydrobenzofuranneolignans Euryalin B

Dihydrobenzofuran neolignans,an important kind of lignans with a variety of biologicalactivitiessuchasanti-oxidation,liver propection,anti-tumor,anti-inflammatory activity and that shows potential medicinal properties in natural medicines.Because of various types of substitutions that can occur on the dihydrobenzofuran ring to make this class neolignans structurally novel with multiple functional groups and chiral centers.These biological and chemical activities reports make the dihydrobenzofuran neolignans attractive for chemical synthesis or modification.In this thesis,we focused on total synthesis of the dihydrobenzofuran neolignans Euryalin B which was extracted from nature.This thesis includes the following parts:Part one is the introduction,which introduces the whole lignans,including its definition,classification,extraction and separation,biological and medicinal activity,synthesis research and background of the dihydrobenzofuran neolignans.And the synthesis of dihydrobenzofuran neolignans were summarized.Then we design the total synthetic of dihydrobenzofuran neolignans Euryalin B combined with previous studies after analysing the target compound's structure.Part two is the section of experiment which is carried out around the first total synthesis of dihydrobenzofuran neolignans Euryalin B.Firstly,thedihydrobenzofuran skeleton was constructed via Knoevenagel condensation and oxidative coupling with vanillin and monoethyl malonate before reducing the double bond of the skeleton structure.Meanwhile,the ligand was constructed via Darzens reaction and Pd/C reduction with monoethyl malonate and methyl chloroacetate.Then the dihydrobenzofuran skeleton and ligand undergoes a Mitsunobu reaction under the catalysis of DEAD,the ester group wasreduced by LiAlH₄ and deprotected with the acid to obtain the target product Euryalin B.The third part is the discussion and analysis of the results including the preparation of special reagents,the optimization of experimental conditions and the discussion of the mechanism of key reactions.Finally,this thesis explored the best reaction strips of the synthetic route and the synthetic method of synthesizing dihydrobenzofuran neolignans was developed,which provided a new synthetic idea for the synthesis of lignans.