Total Synthetic Study Of The Natural Product (+)-Porantheridine And (-)-6-epi-Porantheridine

Piperidine alkaloids are an important class of natural products that generally have potent pharmacological activity.The natural product Porantheridine belongs to the class of tricyclic piperidine alkaloids and was firstly isolated from the genus Poranthera corymbosa by Denne et al in 1972.Structurally,Porantheridine has a 1,3-oxazinidine fused in a tricyclic ring.As a novel tricyclic piperidine alkaloid,Porantheridine has attracted many research groups to conduct synthetic studies over the past few decades.In this paper,a novel and unified synthetic route was designed for alkaloids(+)-Porantheridine and the isomer(-)-6-epi-Porantheridine: starting from the same intermediate,via a Horner-Wadsworth-Emmons / aza-Michael addition reaction or diastereoselective affinity of 2-methoxypiperidine,respectively,followed by same subsequent substrate-controlled reduction,Wacker oxidation and TFA-promoted cyclization,complete their asymmetric total synthesis.Firstly,the total synthesis of racemates was carried out on(±)-Porantheridine and(±)-6-epi-Porantheridine.On this basis,chiral factors were introduced and(R)-tert-butylsulfinamide was used as a hand auxiliary additives,followed by asymmetric addition of silyl dienolates and thionimides,and selective reduction of ?,?-unsaturated double bonds to prepare chiral lactams.Finally the total synthesis of(+)-Porantheridine and(-)-6-epi-Porantheridine was completed.In this paper,the united strategy adopted by the(+)-Porantheridine and isomer(-)-6-epi-Porantheridine asymmetric total synthesis study is novel,feasible,efficient,and is of great significance on asymmetric total synthesis of natural product molecules of other piperidine alkaloids.