Total Syntheses Of Fawcettimine Class Lycopodium Alkaloids And Cyclopiane Class Diterpenes

The Lycopodium alkaloids are a family of structurally unique and biologically active natural products from the genus Lycopodium.Based on the proposed biosynthetic pathway,the Lycopodium alkaloids were divided into four classes.Syntheses of fawcettimine class alkaloids have attracted great attention from synthetic chemists for decades.Cyclopiane class diterpenes were isolated from the fermentation broth of Penicillium,with a novel 6/5/5/5 tetracyclic carbon skeleton and biological activity(antibacterial,antimicrobial).Syntheses of these diterpenes have attracted interest from synthetic chemists.This thesis accomplished the total syntheses of above two classes,a total of seven natural products,1)the asymmetric total syntheses of four fawcettimine calss alkaloids lycojaponicumin C,8-deoxyserratinine,fawcettimine and fawcettidine using divergent strategy;2)the first total synthesis of three Cyclopiane class diterpenes conidiogenone,conidiogenol and conidiogenone B though semipinacol rearrangement and intramolecular aldol cyclizatio as key steps.The following four parts are mainly included in this thesis:1.The isolation,biosynthetic pathway,classification,bioactivity of the Lycopdium alkaloids were introduced briefly.The total syntheses of Lycopdium alkaloids,such as lycopodine,fawcettimine,paniculatine,magellaninone,magellanine,along with the possible biogenetic transformation of fawcettimine class alkaloids and related alkaloids were summarized.2.Study on the syntheses of lycopoine,fawcettimine,fawcettidine were described.Based on the structural difference of lycopoine and fawcettimine,a cyclopropane intermediate was designed for the divergent synthesis.Accordingly,an intramolecular carbene addition/cyclization was developed to efficiently construct cis-6/5 bicyclic,the basic framework of fawcettimine.We also tried to buliding the aza-7-member ring of fawcettidine.3.The asymmetric total syntheses of lycojaponicumin C,8-deoxyserratinine,fawcettimine,fawcettidine were described.Based on the structural feature of those alkaloids,a common 6/5/5 triyclic intermediate was designed and prepared using the intramolecular carbene addition/cyclization and the Dieckmann condensation/Tsuji-Trost allylation as key steps.The target molecules lycojaponicumin C and 8-deoxyserratinine,fawcettimine,fawcettidine were synthesized through regioselective aza-Wittig reaction and Schmidt N insertion,respectively.4.The isolation,bioactivity and structure feature of Cyclopiane class diterpenes were introduced briefly.The 6/5/5/5 tetracyclic framework and three quaternary carbon centers of conidiogenone were rapidly constructed via semipinacol rearrangement and intramolecular aldol cyclization.After some chemical transformations,we completed the first total synthesis of conidiogenone,conidiogenol and conidiogenone B.