Study On The Synthesis Of Lycopodium Alkaloid Lycoplanine A

In this dissertation,the synthesis of Lycoplanine A was investigated via the series reactions including tandem oxidative dearomatization/ Diels-Alder reaction,oxidative cleavage of vicinal diols(Crigee reaction)and macrocycle reaction.The efficient strategies to construct macrocyclic compounds was briefly introduced and the application of various cyclization strategies in the total synthesis of natura1 lproducts was summarized in the review.Seven types of reactions(for example Ring-closing metathesis,Suzuki coupling,Homer-Wadsworth-Emmons Olefination,Diels-Alder Reaction)and their applications in total synthesis of natural products were reviewed in detail from two aspects of the construction of carbon-carbon bonds and carbon hetero-bonds.In the part of experimental study,the isolation and synthesis progress of Lycoplanine A,a Lycopodium alkaloid with unique structure and physiological activity,were briefly introduced.And a plausible biogenetic pathway between Lycoplanine A and Lycopladine H was proposed.A biomimetic strategy was designed according to the possible biogenic relationship,in which the [2.2.2] bridge ring core skeleton of Lycopladine H was constructed by the oxidative dearomatization of phenol in tandem with the Diels-Alder reaction,followed by a synthetic strategy to realize the transformation to Lycoplanine A skeleton by oxidative cleavage.The[2.2.2] bridged ring structure was successfully constructed by tandem oxidative dearomatization/ intermolecular Diels-Alder reaction.However,the 12-membered ring was not constructed via macrolactam reaction.Considering that the two branched chains are located on the different sides of the six-membered ring,and the distance between the twobranched chain is far and not easy to react with each other,a tandem oxidative dearomatization/ intramolecular Diels-Alder reaction was designed to construct a [2.2.2]bridged ring structure,then the Olefin was obtained as macrocyclic substrate with two olefin side chains on the same side.With the olefin in hand,a series of reaction conditions were tested,but the dimerization product was obtained instead of the 12-membered ring skeleton.Based on the above route,in order to solve the problem that the number of cyclized substrate isomers in the ring-closing metathesis is large and difficult to separate,and some reaction sites are not easy to approach,a new Ring-closing metathesis substrate was designed and the synthesis of Lycoplanine A is still on the way.