DMF-Modulated Stereoselective Synthesis Of ?-Kdo Glycosides

3-Deoxy-D-manno-oct-2-ulosonic acid(Kdo),a kind of acidic eight-carbon keto-sugar,is an essential component of bacterial lipopolysaccharide(LPS)and capsular polysaccharide(CPS).Both ?-and ?-Kdo can be found in nature.?-Kdo mostly exists in the inner-core region of gram-negative lipopolysaccharide(LPS);?-Kdo is commonly found in capsular polysaccharides on the surface of bacteria(CPS).Most Gram-negative bacteria contain a common core fragment ?-Kdo-(2?4)-?-Kdo disaccharide and the core disaccharide fragment is further modified by Kdo or other pyranose.Kdo glycosides are closely related to the natural and adaptive immune system and are considered potential targets for the development of carbohydrate vaccines and diagnostic tools.In this paper,a simple and direct method for the synthesis of ?-Kdo glycosides based on the modulation of exogenous DMF has been developed.By screening and optimizing the glycosylation conditions of five different Kdo donors with n-heptanol,a DMF-modulated glycosylation approach using readily available peracetylated Kdo ortho-hexynylbenzoate as donor and SPhosAuNTf2 as a promoter was developed for the stereoselective synthesis of ?-Kdo glycosides.The applicability to the synthesis of ?-Kdo-(2?8)-?-Kdo disaccharide via the"latent-active" strategy has been shown.Mechanistically,the excellent ?-stereoselectivity of the novel glycosylation protocol could be attributed to the formation of imidinium ion in the presence of DMF,which was supported by low-temperature NMR.