Enantioselective Collective Synthetic Studies Toward Longipinane-Type Sesquiterpenoid Marsupellins

This thesis is mainly focused on the enantioselective collective synthetic and biological studies toward longipinane-type sesquiterpenoids marsupellins and.It consists of the following three chapters:Chapter 1 Cp2TiCl-mediated reductive epoxide opening-radical cyclization in natural product synthesis（review）This review mainly introduces the Cp₂TiCl-mediated one-electron reductive radical reaction in total synthesis of natural products.The representative synthetic examples exhibit that Cp₂TiCl-mediated one-electron reductive radical reaction of epoxy and non-epoxy compounds has played an important role in the processes of functional group interconversions,non-and cyclization,including cascade cyclization reaction.Chapter 2 Collective synthetic and biological studies toward longipinane-type sesquiterpenoids marsupellinsA brief introduction of the background for the isolation,structures,biological activities and synthesis developments of longipinane-type sesquiterpenoids marsupellins is provided.After analyzing the molecular structure of these natural products,the collective synthesis strategy was proposed.First,the cis-fused bicyclo[5.4.0]undecenone ring system was constructed through intramolecular Diels-Alder reaction with high stereoselectivity.Second,a Ti（III）-mediated reductive radical cyclization reaction was developed to access the highly-strained bridged cyclobutane moiety.Using this strategy,the 6,6-dimethyltricyclic[5.4.0.0^2,8]undecane core of the longipinane-type sesquiterpenoids was constructed efficiently in only 10 linear steps and can be scaled up to gram-scale preparation。Moreover,the synthesis of 2-acetoxy-4-epi-marsupellol,2-acetoxy-marsupellone and their analogues was achieved.Finally,the anti-alzheimer’s symptoms biological studies of 2-acetoxy-4-epi-marsupellol,2-acetoxy-marsupellone and other longipinane-type sesquiterpenoids derivatives based on the paralytic phenotype induced byβamyloid overexpression in elegans were carried out.Chapter 3 Studies on the asymmetric construction of 6,6-dimethyl dicyclic[5.4.0]undecanone framework of longipinane-type sesquiterpenoidsThis chapter introduces the research progress of asymmetric Diels-Alder catalyzed by Lewis acid.Lewis acids and ligands for Diels-Alder reaction which was used to construct longipinane-type sesquiterpenoids 6,6-dimethyl dicyclic[5.4.0]undecanone skeletons were screened.Finally,the 6,6-dimethyl dicyclic[5.4.0]undecanone framework of longipinane-type sesquiterpenoids was achieved stereoselectively with a good endo selectivity and a high ee value.