Studies On The Asymmetric Total Synthesis Of Monoterpenoid Alkaloids(+)-Arboridinine

Pentacyclic monoterpene alkaloid(+)-Arboridinine contains a indoline and a6/6/7 nitrogen-containing cage-like structure.There are four chiral centers in the molecule,two of which are all-carbon quaternary carbons and one is tertiary hy-droxyl group.Physiological activity tests showed a moderate concentration depend-ent relaxation effect on phenylephrine-induced contraction in isolated rat aortic rings.Organic synthetic chemists have given some attention to this molecule in view of its unique chemical strcuture.Our synthetic strategy is that the[3,3,1]bridged ring structure of the target molecule can be constructed by an intermolecular double-Mannich reaction,and the6/5/6/6 tetracyclic skeleton can be constructed by a Fischer-indole reaction.The cage structure can be constructed through the intramolecular substitution reaction at the3-position of indole.The final hydroxyl structure is constructed by a co-balt-catalyzed decarboxylative acetoxylation reaction.After the chiral substrate was obtained by the asymmetric Michael reaction cat-alyzed by the chiral cinchona base derivative,the first asymmetric total synthesis of(+)-Arboridinine was achieved according to the successful route.This paper mainly includes the following three parts:PartⅠ:Systematically introduced the separation,structural identification,bio-logical activity and reported synthesis of(±)-Arboridinine.PartⅡ:The double-Mannich reaction,the Fischer indole reaction,the S_N2 re-action at the 3-position of indole molecule and the decarboxylation hydroxylation reaction used in this thesis are summarized and enumerated in the application of total synthesis.PartⅢ:The full synthesis of(+)-Arboridinine was carried out using two routes,and the first asymmetric total synthesis of(+)-Arboridinine was finally achieved.The NMR spectra and single crystal diffraction are completely consistent with the reported total synthesis.