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Synthesis of Glycoconjugate Derived Glycans as Molecular Probes

作为分子探针的糖复合物衍生聚糖的合成

基本信息

批准号：
08457590
负责人：
ITO Yukishige
金额：
$ 4.74万
依托单位：
RIKEN (The Institute of Physical and Chemical Research)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

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.

本研究的主要目标是糖蛋白衍生聚糖的合成。在天然低聚糖中发现的多种o -糖苷连锁模式中，甘露糖β-糖苷从合成的角度来看是最具挑战性的。其生物学意义是显而易见的，因为它是所有类型的天冬酰胺连接糖蛋白的核心结构。为了解决这一问题，我们开发了参氧苄基辅助分子内糖苷递送（IAD）。经过多种因素的广泛优化，现在可以合成含二糖（βMan1→4GlcNAc）或三糖（βMan1→4βGlcNAcl→4GlcNAc）的β-甘露糖苷，产率超过80%。我们还确定了混合缩醛的立体化学性质，缩醛是内酰胺的束缚中间体。结合正在进行的低聚糖聚合物载体合成项目，得到了以下结果。1)采用聚合物负载的甘露糖供体，成功地完成了分子内糖苷的递送。该系统专门释放所需的产品，大大简化了分离过程。2)发现了一种新的保护基团——二氯酞酰基，它在固相合成聚乳糖胺型聚糖链中具有潜在的应用价值。3)将本实验室开发的正交糖基化策略扩展到聚合物载体合成。4)合成了负载在聚合物上的唾液酸供体，并将其用于立体选择性糖基化。5)研究了聚合物负载糖基化反应的立体选择性，发现其溶剂效应与固相反应相似。