Total Syntheses Of Lycopodium Alkaloids Phleghenrines A And C

This paper mainly studied the total synthesis of lycodine-type Lycopodium alkaloids phleghenrines A and C.A systematic synthetic study was carried out for the highly strained bicyclo[3.2.2]nonane core skeleton and thermodynamically unfavorable cis-fused hydroquinoline structure of phleghenrines A and C.Through multiple attempts,the total synthesis of the above molecules was finally achieved,and the enantioselective preparation of chiral intermediate 2-98*was completed based on this.The paper contains the following three chapters:Chapter 1 Construction strategy of 4a,8a-cis-hydroquinoline structure in alkaloids（review）This chapter provides a brief overview of common strategies for the construction of4a,8a-cis-hydroquinoline structures.These include the Diels-Alder reaction,intramolecular[3+2]reaction,rearrangement reaction,tandem cyclization reaction,and other strategies.Chapter 2 Synthetic Studies on Lycopodium Alkaloids Phleghenrines A and CThis chapter describes the background research on Lycopodium alkaloids and the common strategies used to construct the Lycopodium alkaloid of the lycodine type.Based on these strategies,a systematic synthesis study was conducted on the bicyclo[3.2.2]nonane core and cis-fused hydroquinoline structure of phleghenrines A and C.The synthesis of the cis-fused hydroquinoline structure was completed twice by Diels-Alder reaction and Diels-Alder reaction combined with Beckmann rearrangement.Various strategies such as intramolecular condensation reaction,[4+3]cycloaddition reaction,cyclopropanation/Sm I₂-mediated reductive cleavage of the cyclopropane ring,intramolecular reductive Heck reaction,and intramolecular 1,4-addition reaction were attempted,and ultimately,the highly strained bicyclo[3.2.2]nonane core skeleton was constructed by Diels-Alder reaction and Tiffeneau-Demjanov rearrangement.In addition,for the synthesis of the A ring,the hetero-Diels-Alder reaction was innovatively introduced into the total synthesis of Lycopodium alkaloids.Finally,by three highly stereoselective[4+2]cyclization reactions and two relatively stereospecific ring-expansion rearrangements,the first total syntheses of Lycopodium alkaloids phleghenrines A and C were accomplished in a divergent manner with total yields of 1.2%and 0.3%in 19 and 18 steps,respectively.Chapter 3 Asymmetric Synthetic Studies on Phleghenrine alkaloidsThis chapter introduces common strategies for asymmetric synthesis and the current research status of catalytic asymmetric Diels-Alder reactions using non-substituted cyclopentenone as dienophiles.Based on the racemic synthesis route of phleghenrines A and C,various strategies such as asymmetric organocatalysis and metal catalysis were attempted.Ultimately,the enantioselective preparation of the key chiral precursor was accomplished using a chiral auxiliary-controled strategy,making the asymmetric total synthesis of phleghenrines A and C possible.During this process,the one-pot removal of 3-sulfonyl-1,3-oxazolidine unit using p-HOC₆H₄CO₂H-HBr/HOAc system was also reported for the first time.