The Studies Towards The Total Synthesis Of Camptothecin,Nauclea And Protoberberine Family Of Alkaloids And Cyclooctane-containing Sesterterpenoids

Part 1:The studies towards the total synthesis of camptothecin,nauclea and protoberberine family of alkaloids.A unified and convergent strategy was developed,using a cascade exo-type hydroamination followed by a spontaneous lactamization as key step.This methodology was used to achieve the total synthesis of camptothecin and six biogenetically or structurally related natural alkaloids,as well as 35 members of natural product-like molecules.In the process of total synthesis of camptothecin,we explored three synthetic routes.In the first two routes,E fragment formation was full of difficulty and functional group transformation was troublesome after cascade cyclization.We introduced a suitabale oxidation state on E ring in the third route,and furnished camptothecin in 9 steps and 15%total yield.The late-stage modification of camptothecin skeleton was carried out,which may provide new opportunity to remould the structure of camptothecin.We believe that this methodology can open new research avenues into the medicinal chemistry research of camptothecin,nauclea and protoberberine-family natural products.Part 2:The studies towards the total synthesis of cyclooctane-containing sesterterpenoids.We utilized a tandem ring closing metathesis of dienynes to provide the basic skeleton of cyclooctane-containing sesterterpenoids.Via adjusting the steric hindrance of alkene and substituent of alkyne,we prepared the basic 5-8-5 skeleton of ophiobolin A in 12 steps and 13%total yield,and the basic 5-8-6-5 skeleton of variecolin in 13 steps and 28%total yield.The strategy we used in constructing the eight-membered ring and the all-carbon quaternary center may provide a reference for the total synthesis of these natural products.