Tandem Reaction For The Construction Of Disubstituted Indoles And Studies Toward Total Synthesis Of Lucidumone And Akuammiline Alkaloids

In this thesis,a method for constructing the 2,3-disubstituted indoles was established via a tandem reaction,and the total synthesis of lucidumone and the akuammiline alkaloid were also explored.The thesis consists of the following four chapters:Chapter 1 Oxygenation of unactivated Csp~3-H bonds and its application in total synthesis of natural productsThe application of oxygenation of unactivated Csp~3-H bonds in total synthesis of natural products in recent years was reviewed which could shorten the synthesis route and improve the synthesis efficiency.And the review was divided into two categories based on the presence of directing group with more detailed explanation,which provided an important background for the follow-up research work.Chapter 2 Synthesis of 2,3-disubstituted indoles via a tandem reactionThe substructures of substituted indole skeleton are widely existed in monoterpene indole alkaloids.Developing an efficient method to synthesize substituted indoles would be of great significance.A strategy for the synthesis of2,3-disubstituted indoles from 2-(2-nitrophenyl)cyclohexane-1,3-dione was developed.A wide array of 2,3-disubstituted indoles were accessed in good yields via a tandem reduction/condensation/fragmentation/cyclization sequence.The utility of this strategy was exemplified in formal syntheses of leucomidine A and goniomitine.The mechanism was confirmed by experiments and density functional theory(DFT)calculations.Chapter 3 Studies toward the total synthesis of lucidumoneThe meroterpenoid lucidumone selectively inhibits COX-2 and has an unprecedented caged polycyclic ring system.Using phenol as starting material,the framework of the lucidumone was constructed by oxidative dearomatization/IMDA reaction,Cu-mediated remote C-H hydroxylation,allyl oxidation,acid-promoted dynamic kinetic resolution cyclization and benzylic oxidation.At the same time,we also made a preliminary exploration of the late stage C-H oxidation to install the hydroxyl group.Chapter 4 Studies on the divergent synthesis of akuammiline alkaloidsThe akuammiline alkaloids are a kind of monoterpenoid indole alkaloids with extensive bioactivities,which would be used as a potential sources of pharmaceutical compounds.A brief introduction of the background for the isolation,structures and plausible pathway for the biogenesis of akuammiline alkaloids was provided.The synthetic studies towards the divergent synthesis of akuammiline alkaloids have been explored via aza-Michael addition/α-arylation of carbonyl,C-C bond activation and catellani reaction.