Enatioselective Total Synthetic Studies Toward Gardneria Monoterpenoid Indole Alkaloids Gardmultimine A

Gardneria plants,abundant species in the regions of Asia,are one of the key sources of alkaloids containing a monoterpene indole skeleton.These alkaloids have attracted great attention due to the structural complexity and biological significance.In 2016,Gardmultimine A as a significant spirooxindole alkaloids was first isolated by Chinese organic chemists.This pentacyclic alkaloid has 12-methoxy-substituted spirooxindole and azabicyclo[2.2.2]octane core,to some extent,demonstrating a challenge from a synthetic point of view.This thesis mainly aims at the synthetic study of Gardmultimine A,in which the C-H borylation、oxidative rearrangement and an Au(I)-catalyzed Conia-ene-type 6-exo-dig cyclization as key steps were applied to the first asymmetric total synthesis of Gardmultimine A.The strategy of collective synthesis of Gardmultimine A monoterpenoid indole alkaloids was also explored.The contents were listed as follows: Chapter 1.Synthetic Developments of Spirooxindole alkaloids(review)According to different strategies for the synthesis of spirooxindole system,the synthetic developments of spirooxindole alkaloids are reviewed.Chapter 2.Studies on Asymmetric Total Synthesis of Gardneria Monoterpenoid Indole Alkaloids Gardmultimine AA brief introduction of the background for the isolation,structures,biological activities and biogenetic of gardneria monoterpenoid indole alkaloids was provided.The first asymmetric total synthesis of gardmultimine A has been achieved in 19 steps and 0.1% overall yield from D-tryptophan.The synthesis fetures an Ir-catalyzed regioselective C-H borylation,a stereocontrolled oxidative rearrangement and an Au(I)-catalyzed regioselective Conia-ene-type 6-exo-dig cyclization.Chapter 3.Collective Synthesis of Gardneria Monoterpenoid Indole AlkaloidsBased on the total synthesis of Gardmultimine A,the collective synthesis strategy of gardneria monoterpenoid indole alkaloids was proposed.The tetracyclic spirooxindole skeleton was constructed through Fischer indole synthesis,dihydroxylation and pinacol rearrangement.This work is on going.