A simple and direct DMF-modulated α-selective Kdo glycosylation approach for the stereoselective synthesis of the α-linked Kdo glycosides is developed. Glycosylation of the readily available peracetylated Kdo ortho-hexynylbenzoate with common acceptor alcohols using SPhosAuNTf2 as a promoter and DMF as a modulating molecule afforded a range of Kdo glycosides with good α-selectivities. Furthermore, the present method is effectively applied in the latent-active synthesis of the α-linked di-Kdo glycoside bearing a linker at the reducing end. Finally, the first observation of a Kdo imidinium ion in the low-temperature NMR provides evidence for the plausible mechanism of the DMF-modulated α-selective Kdo glycosylation.

Glycosidation plays a pivotal role in the synthesis of O-glycosides and nucleosides that mediate a diverse range of biological processes. However, efficient glycosidation approach for the synthesis of both O-glycosides and nucleosides remains challenging in terms of glycosidation yields, mild reaction conditions, readily available glycosyl donors, and cheap promoters. Here, we report a versatile N-iodosuccinimide/trimethylsilyl triflate (NIS/TMSOTf)-promoted glycosidation approach with glycosyl ortho-hexynylbenzoates as donors for the highly efficient synthesis of O-glycosides and nucleosides. The glycosidation approach highlights the merits of mild reaction conditions, cheap promoters, extremely wide substrate scope, and good to excellent yields. Notably, the glycosidation approach performs very well in the construction of a series of challenging O- and N-glycosidic linkages. The glycosidation approach is then applied to the efficient synthesis of oligosaccharides via the one-pot strategy and the stepwise strategy. On the basis of the isolation and characterization of the departure species derived from the leaving group, a plausible mechanism of NIS/TMSOTf-promoted glycosidation of glycosyl ortho-hexynylbenzoates is proposed.

Highly convergent synthesis of a β-mannuronic acid alginate hexadecasaccharide representing the longest synthetic polymannuronic acid so far is achieved.

Pseudomonas aeruginosa is a leading cause of urinary tract, pulmonary, and wound infections and is becoming increasingly resistant to antibiotics. Here, we report the iodonium- and gold(I)-promoted bimodal glycosylation of glycosyl (Z)-ynenoates for highly β-selective promoter-controlled synthesis and antigenic evaluation of a series of 1,2-cis-β-linked mannuronic acid alginate glycans of P. aeruginosa up to a 24-mer, which represents the longest polymannuronic acid synthesized to date. By screening the six synthetic mannuronic acid alginate glycans with the mouse serum antibodies, we identified the mannuronic acid tetrasaccharide as the optimal antigen epitope for the development of vaccines against P. aeruginosa.

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