Synthesis of Glycoconjugate Derived Glycans as Molecular Probes

糖蛋白聚糖的合成一直是本研究的主要目标，在天然存在的寡糖中发现的各种O-糖苷键模式中，甘露糖的β-糖苷从合成的角度来看是最具挑战性的。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的糖蛋白的核心结构而存在。我们开发了对甲氧基苄基辅助的分子内糖苷配基递送（IAD）来解决这个问题。通过对几个因素的优化，目前已能以80%以上的产率合成含双糖（β Man 1 →4GlcNAc）或三糖（β Man 1 →4β GlcNAc l →4GlcNAc）的β-甘露糖苷。我们还指定了IAD中的栓系中间体混合缩醛的立体化学。结合正在进行的聚合物支持合成寡糖的项目，获得了以下结果：1）使用聚合物支持的甘露糖供体成功地进行了分子内糖苷配基递送。该系统特异性地释放所需产物并大大简化了分离过程。2）新的保护基团，二氯邻苯二甲酰基团被开发，这是潜在的有用的固相合成的聚乳糖胺型聚糖链。3）正交糖基化策略，这是以前在这个实验室开发的扩展到聚合物支持合成。4）5）研究了聚合物支载糖基化反应的立体选择性，发现其具有与液相反应相似的溶剂效应。

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.