NIS/TMSOTf-Promoted Glycosidation of Glycosyl ortho-Hexynylbenzoates for Versatile Synthesis of O-Glycosides and Nucleosides.

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.

Synthesis of l-glycero- and d-glycero-d-manno-Heptose Building Blocks for Stereoselective Assembly of the Lipopolysaccharide Core Trisaccharide of Vibrio parahemolyticus O2.

Synthesis of bacterial cell surface l-glycero-d-manno-heptose (l,d-Hep)- and d-glycero-d-manno-heptose (d,d-Hep)-containing higher carbon sugars is a challenging task. Here, we report a convenient and efficient approach for the synthesis of the l,d-Hep and d,d-Hep building blocks. Using l-lyxose and d-ribose as starting materials, this approach features diastereoselective Mukaiyama-type aldol reactions as the key steps. On the basis of the synthetic l,d-Hep and d,d-Hep building blocks, we achieved the first stereoselective synthesis of the unique α-l,d-Hep-(1→3)-α-d,d-Hep-(1→5)-α-Kdo core trisaccharide of the lipopolysaccharide of Vibrio parahemolyticus O2.

Dimethylformamide-Modulated Kdo Glycosylation for Stereoselective Synthesis of α-Kdo Glycosides.

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.

Gold(i)-promoted α-selective sialylation of glycosyl ortho-hexynylbenzoates for the latent-active synthesis of oligosialic acids.

A gold(i)-promoted α-selective sialylation approach with 5-N,4-O-oxazolidinone-protected sialyl ortho-hexynylbenzoates as donors is described for the stereoselective synthesis of α-sialosides. Iterative couplings of the 'active' sialyl ortho-hexynylbenzoates and the 'latent' sialyl ortho-iodobenzoates provide a new approach for the 'latent-active' synthesis of α-(2 → 9)-linked oligosialic acids that are relevant to N. meningitidis serogroup C capsular polysaccharide.

Synthesis of the ß-linked GalNAc-Kdo disaccharide antigen of the capsular polysaccharide of Kingella kingae KK01.

The first construction of the challenging ß-(1 → 5)-linked GalNAc-Kdo skeleton is described for the synthesis of the disaccharide antigen of the capsular polysaccharide of Kingella kingae KK01. TfOH-catalyzed glycosylation of N-Troc-protected d-galactosaminyl N-phenyl trifluoroacetimidate with a sterically hindered 5-hydroxyl group of the ß-Kdo building block in toluene proceeded smoothly to provide the desired disaccharide in excellent yield with satisfactory ß-selectivity. An optimal sequence for the deprotection of the disaccharide skeleton was found to access the disaccharide antigen of Kingella kingae KK01 for further immunological studies.

Synthesis of 3- C-Branched Kdo Analogues via Sonogashira Coupling of 3-Iodo Kdo Glycal with Terminal Alkynes.

A highly efficient approach for the synthesis of 3- C-branched mono- and di-3-deoxy-d- manno-oct-2-ulosonic acid (Kdo) enyne analogues is developed for the first time based on Sonogashira coupling of terminal alkynes with 3-iodo Kdo glycal obtained by the NIS/TMSOTf-promoted one-step reaction from peracetylated Kdo ethyl ester. Further transformation of 3- C-branched mono- and di-Kdo enyne analogues by asymmetric hydrogenation and saponification provided 2-deoxy-ß-carboxyl Kdo analogues in a stereocontrolled mode.

Gold(I)-catalyzed synthesis of ß-Kdo glycosides using Kdo ortho-hexynylbenzoate as donor.

A gold(I)-catalyzed glycosylation of Kdo with glycosyl ortho-hexynylbenzoate as donor is reported. The couplings of Kdo ortho-hexynylbenzoate with a set of alcohols promoted by PPh3AuOTf afford Kdo glycosides with good ß-selectivities. This glycosylation method allows for the synthesis of ß-Kdo monosaccharide with a C5 linker at the reducing end for subsequent conjugation to carrier proteins and arrays.