Polytetrafluoroethylene-Assisted Rapid Preparation of α‑Oligomannosides Containing Mannose-6-Phosphate Residues

A Polytetrafluoroethylene (PTFE)-assisted "liquid-phase reaction, solid-phase separation" strategy was used to streamline the assembly of mannose-6-phosphate mannosides isolated from Pichia holstii NRRL Y-2448. Thus, the α-stereoselective tetramannoside and pentamannoside scaffolds were rapidly assembled with an average yield of 90% per step through neighboring group participation (NGP) or remote group participation (RGP), as well as regulation of the reactivities of glycosyl donors or acceptors. Notably, a gram-scale preparation of protected pentamannoside 16 was accomplished, and the average yield per step exceeded 92%. Furthermore, the pentamannoside and tetramannoside were phosphorylated and purified by PTFE-assisted filtration, demonstrating the high efficiency, simplicity, and universality of the purification strategy for well-defined glycan synthesis. The efficient assembly of mannose-6-phosphate mannoside paves the way for uncovering the biological function of phosphorylated glycans.