Synthetic Studies Towards Lundurine And Related Alkaloids

With diverse complex molecular structures and promising bioactivities,Kopsia indole alkaloids have attracted considerable attention from chemists.Lundurines A-D are the monoterpenoid indole alkaloids isolated from plants of Kopsia tenuis.They share an aza cyclooctane,a pyrrolidine ring,and an unprecedented cyclopropane being fused to the indoline moiety,which was unusal in millions of known natural products.They have four stereocenters,three of which are located in pentasubstituted cyclopropane.Additionally,several structurally and biogenetically related alkaloids,lapidilectine and grandilodine-type ones,also sever as the research targets for chemists.Extensive explorations on the chemical synthesis and the biogenetic relationship of them,especially on the generation mechanism of the cyclopropyl ring in lundurines,were implemented and remarkable breakthrough was made.This dissertation possesses three chapters.In the Chapter 1,a brief introduction of Kopsia indole alkaloids and a classification of their structural types were given.In the Chapter 2,we reviewed the previously reported work on the synthesis of lundurine and related alkaloids,and summarized their synthetic strategies,routes,highlights,and inspirations to our work.In the Chapter 3,we described an in-depth exploration of the synthetic study towards lundurines A-D and tenuisines A-C.Using L-pyroglutamic acid derived from the chiral pool,we established the first chiral quaternary carbon center and the desired Z-vinyl iodide.The linkage of the two fragments and the construction of the pyrrolidone ring were achieved through a tandem reductive amination/lactamization sequence.After that,the eight-memberd ring was forged via a palladium-catalyzed intramolecular direct C-H vinylation.The pentasubstituted cyclopropanyl ring was installed by a late-stage Lewis acid promoted formal[3+2]cycloaddition/N₂ extrusion process.Adjustment of the oxidation states of the pyrrolidone afforded lundurines A-C while the synthetic attempts toward lundurine D via the introduction of methoxyl at C11-position were failed.With the 6/5/8/5 tetracyclic framework in hand,we explored a strategy featuring the dearomatization of indole,ring closure of the D ring and then the C ring,for the total synthesis of tenuisines A-C.However,extensive attempts toward oxidative or halogenative dearomatization,radical addition,[3+2]or[2+2]cycloaddition,（reductive）Heck reaction,and Hock rearrangement of 1,2-dioxole,failed to work.