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合成糖蛋白衍生的聚糖。在天然存在的寡糖中发现的各种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，因为其生物学意义是显而易见的。它作为所有类型的天冬酰胺连接糖蛋白的核心结构而存在，经过广泛优化，我们开发了对甲氧基苯甲基辅助的糖苷配基递送（IAD）。在几个因素的影响下，现在可以合成含有二糖（βMan1→4GlcNAc）或三糖（βman1→4βGlcNAcl→4GlcNAc）的β-甘露糖苷，其收率超过80％，我们还指定了混合缩醛（即束缚的）的立体化学。 IAD 中的中间体与正在进行的低聚糖聚合物支持合成项目相关，获得了以下结果。1) 分子内使用聚合物支持的甘露糖供体成功地进行了苷元递送。该系统专门释放所需的产物并极大地简化了分离过程。2)开发了一种新的保护基团二氯邻苯二甲酰基团，该基团可用于聚乳糖胺型聚糖链的固相合成。 3) 将本实验室先前开发的正交糖基化策略扩展到聚合物支持合成。4) 合成了聚合物支持的唾液酸供体并用于立体选择性糖基化。5)研究了聚合物支持的糖基化反应的立体选择性，发现其具有与溶液相反应相似的溶剂效应。