Study On The Metal-catalyzed Synthesis Of Acyl C-glycosides And Alkynyl C-glycosides

Compared with O-glycosides,C-glycosides are metabolically stable and have great potential in drug development and chemical biology.Due to the lack of effective synthesis methods,C-acyl glycosides and C-alkynyl glycosides are two types of C-glycosides that have been less studied.This thesis is devoted to the development of efficient transition metal-catalyzed methods for the construction of these two types of C-glycosides,which can be divided into two parts as follows.(1)We demonstrated that Liebeskind-Srogl coupling is well-suited for the synthesis of(nonclassical)-C-acyl glycosides.The reaction occurs at ambient temperature and is base-free,stereo-retentive and compatible with a broad range of(hetero)aryl boronic acids and carbohydrate-derived thioesters.The synthesis of challenging acylated(nonclassical)C-acyl glycosides is achieved,avoiding functionality compatibility problems and the elimination side reaction.We have improved the synthesis of scleropentaside A and obtained enough quantity of this natural product for the bio-activity study(DPPH assay),which shows that scleropentaside A exhibited moderate antioxidant activity,whereas its dehydrated analog showed no activity at all.(2)We developed a visible light/Cu synergistic catalyzed dehydroxylative alkynylation reaction to construct C-alkynyl glycosides with 1-hydroxy carbohydrates and terminal alkynes as starting materials at room temperature.The advantage of this strategy is that the simple and easy-to-prepare 1-hydroxy carbohydrates are used as radical precursors,which are directly coupled with the terminal alkyne after NHC activation.Further studies showed that the method could be applied to non-carbohydrate substrates: primary,secondary and tertiary alcohols undergo the desired dehydroxylative alkynylation smoothly.The work carried out in this thesis not only enriches the toolbox of Cglycoside synthesis,but also provides new ideas for the subsequent research of our group.