Total Syntheses Of Paeoveitol,Cedranes And Przewalskone Via Cycloaddition Strategy

The cycloaddition reaction is one of the most efficient chemical transformations,which can form multiple carbon-carbon bonds or carbon-heteroatom bonds in one single reaction.This thesis aims at using[4+2]and[5+2]cycloaddition strategies to synthesize Paeoveitol,Cedranes,and Przewalskone.These compounds have unique novel frameworks and good biological activities.Besides,the[4+2]and[5+2]cycloaddition reaction of phenol derivatives was reviewed.This paper includes four chapters as follows:Chapter 1 Biomimetic Synthesis of norditerpene PaeoveitolPaeoveitol and Paeoveitol A-E,which were isolated from the root of Paeonia veitchii by Chen group,are a series of nature products with potential biogenic relationships.Among them,Paeoveitol is a pair of new norditerpene enantiomers with6/5/6/6 fused tetracyclic ring skeleton and bearing three continuous chiral centers.Inspired by the biosynthetic pathway,it is speculated that Paeoveitol can be obtained by[4+2]cycloaddition reaction between Paeoveitol D and compound 1-49.Therefore,starting from p-Toluquinone and 2-Methylhydroquinone,Paeoveitol D and compound 1-49 were synthesized by five steps respectively.Under heating,the o-QM intermediate formed from compound 1-49 with Paeoveitol D undergoing a hetero-Diels-Alder reaction,then successfully construct the chromane in the target molecule,which proceeds with high regio-and diastereoselectivity.After removing the acetyl group,we achieved biomimetic total synthesis of the Paeoveitol in 7 steps with 26%yield.In addition,we also explored the hetero-Diels-Alder reaction catalyzed by Lewis acid,chiral Br?nsted acid and organometallic reagents.Chapter 2 Total Syntheses of CedranesCedrane natural products embody noval tricyclo[5.3.1.0^1,5]undecane subunits.Among them,8,14-Cedranoxide has a complex 8-oxa-tetracyclo[7.2.2.0^1,5.0^6,13]tridecane system,containing six consecutive chiral centers,two of which are all-carbon quaternary stereogenic center,one is the oxygenated quaternary carbon stereogenic center.In this chapter,we obtained phenol derivatives 2-48 by using R-citronellal as the starting material,sequenced by asymmetric Michael addition catalyzed by small organic molecules,Aldol reaction,1,2-addition,oxidative aromatization and allyl oxidation.In the study of the cyclization of this compound,we found that the intramolecular oxidation[5+2]cycloaddition and etherification reactions performed under oxidation of the high-valent iodine reagent.Stereospecifically yields compound2-49,five continuous chiral centers and three five-membered rings were constructed in one step.Reducing the carbonyl group and double bond of olefin in 2-49,the sesquiterpene compound 8,14-Cedranoxide was successfully obtained.8,14-Cedranolide,8,14-Cedranediol were synthesized from 8,14-cedranoxide.Chapter 3 Study Towards the Total Synthesis of PrzewalskonePrzewalskone,an unprecedented adduct of danshenol type terpenoid and Przewalskin E via a hetero-Diels–Alder cycloaddition was isolated from the roots of Salvia przewalskii and displayed significant cytotoxic activities against five human cancer lines in the bioassay.Inspired by the biosynthetic pathway,Przewalskone may be derived from the formal[4+2]cycloaddition reaction with Tanshinone I or its derivatives and icetexane diterpene Brussonol or Przewalskin E.A hetero-Diels-Alder reaction can be performed with o-benzoquinone and olefin to produce benzodioxin.But o-benzoquinone with less active furan or benzofuran to produce a benzodioxin derivative via a hetero-Diels-Alder reaction is extremely rare.We studied the hetero-Diels-Alder reaction of furan derivatives and found that there are two possible reaction mechanisms:（1）Furan derivatives and catechol undergo the free radical cyclization under FeCl₃ catalysis to obtain benzodioxin derivative;（2）The furan derivative and o-benzoquinone undergo a hetero-Diels-Alder reaction under heating.Due to the low activity of furan and the instability of catechol（o-quinone）,both reactions limited by the scope of substrates and low yield.The current good result is the completion of the hetero-Diels-Alder reaction between intermediate 3-103 and Przewalskin E,and subsequent research is still ongoing in our liboratory.Chapter 4 Review of Cycloaddition of Phenol derivativesThe cycloaddition reaction is widely used in the syntheses of natural products because it can quickly construct multiple carbon-carbon bonds or carbon-heteroatom bonds in one single step.This chapter mainly reviews the research progress of[4+2]and[5+2]cycloaddition reactions of phenol derivatives,mainly focuses on their application in the syntheses of natural products.