Interrupted Pummerer 反应在标签辅助的寡糖合成中的应用

寡糖的自动化合成研究远滞后于蛋白和核酸，仍然面临巨大的挑战。 近年来，传统的固相合成策略的局限性也促使新的策略比如标签辅助的合成策略的发展。这一策略结合了固相和液相合成的优点，即保证了高的反应活性及易监测性，也易于快速分离。基于我们最近发展的一种基于interrupted-Pummerer反应的新颖的糖苷化策略，我们期望进一步系统性的研究这一糖苷化方法在标签辅助的寡糖合成策略包括氟负载策略、疏水基团辅助策略及离子液负载策略的可行性。本项目计划通过利用interrupted-Pummerer反应介导的糖苷化方法，发展一种可回收、可再生和不需过渡金属催化切断的连接臂，结合不同的标签辅助寡糖组装策略的内在优势，推动寡糖自动化液相合成相关研究。

Despite great efforts have been made，automated oligosaccharide synthesis is still a big challenge and remains less explored if compared to automated protein and nucleic acid synthesis。The shortcomings associated with the nature of the heterogeneous conditions required for the traditional solid-phase based technology have recently stimulated the discovery of the solution-phase based oligosaccharide assembly strategy which incorporated the advantages of both solid-phase and liquid-phase synthesis。Recently, we have developed a novel glycosylation reactions for oligosaccharide assembly based on interrupted-Pummerer reaction。In this proposal，we will investigate the possibility of apply this newly development glycosylation reaction in solution-phase based oligosaccharide synthesis。Several solution-phase based strategies including fluorous-tag assisted method，hydrophobically assisted switching of phase (HASP) and ionic liquid supported method will be systematically examined and new assembly strategies will be tested. Most importantly, new types of linker which could possibly be cleaved under mild conditions without transition metal catalyst and could be recovered and regenerated will be designed.