Synthetic Studies Toward Tetrazomine,Quinocarcin And Reniecramycin G Throgh Pd-Catalyzed C(sp~3)-H Functionalizations

Transition-metal-catalyzed C-H functionalization has emerged as an efficient and atom economic method for preparing natural compounds and pharmaceutical targets.The application of C-H functionalization in total synthesis of natural products has attracted much attention.Tetrahydroisoquinoline alkaloids have attracted wide attention over the past 30 years during to their biological activity.In thid paper by applying the Pd-catalyzed C-H functionalization to the synthesis of tetrahydroisoquinoline alkaloids.we have finished the scalable synthesis of(-)-Tetrazomine and(-)-Quinocarcin,and the synthetic studies toward the(-)-Renieranycin G.Including the follow three parts:1).Scalable synthesis of(-)-Tetrazomine.Frist we used Pd-catalyzed C-H arlytion to synthesize phenylalanine analogues,then we used Pictet-Spengler reaction to constructe tetrahydroisoquinoline.Combining with the Cu-catalyzed asymmetric multicomponent[C+NC+CC]coupling reaction,we had finished the asymmetric synthesis of functionalized pyrrolidines.3-hydroxypiperidic acid another part of(-)-Tetrazomine was constructed by Pd-catalyzed C-H acetoxylation.By the amide condensation reaction,we had finished the scalable synthesis of(-)-Tetrazomine.2).Scalable synthesis of(-)-Quinocarcin.Because the core syructure of(-)-quinocarcin and(-)-Tetrazomine are alike,so we use tsimilar strategy to synthesis(-)-quinocarcin.Frist we used Pd-catalyzed C-H arlytion to synthesize phenylalanine analogues,then we used Pictet-Spengler reaction to construct tetrahydroisoquinoline.Combining with the Cu-catalyzed asymmetric multicomponent[C+NC+CC]coupling reaction,we finished the scalable synthesis of(-)-Quinocarcin.3).The synthetic studies toward the synthesis of(-)-Renieranycin G.We used Pd-catalyzed C-H arylation to synthesize phenylalanine analogues,then we used Pictet-Spengler reaction to constructe tetrahydroisoquinoline.Next,we dimerized the two fragments to obtain the key structure.We have preliminarily explored the feasibility of the synthesis of(-)-Renieranycin G though Pu-Catalyzed C(sp3)-H Functionalizations.