Synthesis of Glycoconjugate Derived Glycans as Molecular Probes

本研究的主要目标是合成糖蛋白衍生的多糖。在天然低聚糖中发现的多种O-糖苷连接模式中，从合成的角度来看，甘露糖的β-糖苷是最具挑战性的。它的生物学意义是显而易见的，因为它作为所有类型的天冬酰胺连接糖蛋白的核心结构存在。为了解决这一问题，我们开发了对甲氧基苄基辅助分子内苷元递送(IAD)。经过多个因素的优化，现在可以合成含有二-(β-Man1-β-4GlcNAc)或三糖(β-man1-→-4GlcNAc)的β-甘露糖苷，产率在80%以上。我们还指定了混合缩醛的立体化学，它是IAD中的拴系中间体。结合正在进行的聚合物支撑体合成低聚糖的项目，获得了以下结果：1)利用聚合物支撑体甘露糖供体成功地进行了分子内苷元传递。2)开发了一种新的保护基团--二氯邻苯二甲酰基，可用于固相合成聚乳糖胺型糖链。3)将本实验室开发的正交糖基化策略扩展到聚合物载体的合成。4)合成了聚合物载体上的唾液酸供体，并将其用于立体选择性糖基化反应。5)考察了聚酰胺支载糖基化反应的立体选择性，发现其与溶液相反应具有相似的溶剂效应。

The major target in this research has been the synthesis pf glycoprotein derived glycans.Among variety of O-glycoside linkage patterns found in naturally occurring oligosaccahrides, β-glycoside of mannose is the most challenging from synthetic point of view. Its biological significance is obvious because it exists as the core structure of all types of asparagine linked glycoproteins. We have developed paramethoxybenzyl assisted intramolecular aglycon delivery (IAD) to solve this problem. After extensive optimization of several factors, it is now possible to synthesize β-mannoside containing di- (βMan1→4GlcNAc) or trisaccharide (βman1→4βGlcNAcl→4GlcNAc) in more than 80% yield. We have also assigned the stereochemistry of the mixed acetal which is the tethered intermediate in IAD. In connection with ongoing project on polymer support synthesis of oligosaccharides, following results were obtained.1) Intramolecular aglycon delivery was successfully performed using polymer supported mannose donor. This system specifically releases the desired product and greatly simplifies the isolation process.2) A new protecting group, dichlorophthaloyl group was developed which is potentially useful for solid phase synthesis of polylactosamine type glycan chains.3) Orthogonal glycosylation strategy which was previously developed in this laboratory was extended to polymer support synthesis.4) Sialic acid donor supported on polymer was synthesized and used for stereoselective glycosylation.5) Stereoselectivity of polyme supported glycosylation reaction was investigated and discovered to have similar solvent effect as solution phase reactions.