Total Synthesis Of Codonopiloneolignanin A

Lignins are a series of natural products formed by the polymerization of two molecules of phenylpropanoid derivatives?C6-C3 monomers?.It is a phytoestrogen that has the effects of scavenging free radicals and anti-oxidation in the body.They have a variety of biological activities,such as lignans can bind estrogen receptors and interfere with cancer promoting effects.In this thesis,Codonopiloneolignanin A,a rare natural lignan natural product,is used as the target molecule for total synthesis research.And the research progress of the asymmetric Stetter reaction catalyzed by nitrogen heterocyclic carbene?NHC?is reviewed.This thesis is divided into two parts:Chapter I Total Synthesis of Codonopiloneolignanin ACodonopiloneolignanin A is the first neolignan with unique structure isolated from the water extract of Dangshen in Weiyuan County,Gansu Province in 2015 by Shi's research group.It has the following three characteristics:?1?The content is extremely scarce?only 0.8mg is isolated from 50kg Dangshen?;?2?Novel structure(the first has a tricyclic[5,3,0,0^3,8]decane skeleton)and contains four consecutive chiral centers;?3?There is no relevant report on biological activities.Combining these three factors,this neolignan aroused our synthetic interest.Combined with the biogenic synthesis pathways speculated in the separation literature and the structural characteristics of the target molecules,we designed the use of[4+3]cycloaddition or free radical cyclization reactions to construct tricyclic[5,3,0,0^3,8]decane skeleton.Unfortunately,the cyclization precursors of these two cyclization methods are difficult to prepare,and the cyclization precursor compounds have not been successfully synthesized after many attempts.Subsequently,3,4,5-trimethoxycinnamaldehyde?115?was used as the raw material,and the two-membered five-membered ring?116?with benzene ring in cis was dimerized after catalyzed by nitrogen heterocyclic carbene After a few steps of conversion,the all-cis five-membered cyclic aldehyde?107?was obtained.107 undergoes double Friedle-Crafts reaction under acidic conditions and also removes the TBS protecting group.We have achieved the total synthesis of the target molecule Codonopiloneolignanin A.In addition,we also studied the reductive coupling-cyclization reactions of 3,4,5-trimethoxyphenylpropionic acid methyl ester under SmI₂-mediated and found that the main product was trans-cyclization Dimer.Chapter II Research Progress of the Asymmetric Stetter Reactions Catalyzed by N-Heterocyclic carbenesN-heterocyclic carbene?NHC?is a class of small organocatalysts.In recent years,chiral N-heterocyclic carbene catalysts have been greatly developed,especially in the asymmetric Stetter reaction.This chapter mainly introduced the research progress of asymmetric intermolecular and intramolecular Stetter reactions catalyzed by chiral NHCs for the past two decades.