Synthesis of oligosaccharides by using solid-phase method and hybrid method of solid-phase and liquid-phase

研究了固相法和固液混合法对低聚糖的高效合成。我们之前建立了“化学钓鱼”方法，利用固载磷化氢与叠氮化物之间的特异性反应，选择性地从反应混合物中捞出所需的具有叠氮化物功能的化合物。该方法应用于引发子五糖的固相合成。对糖蛋白n -链低聚糖的合成进行了研究。以（Bu_3Sn）_2为原料，建立了一种自由基裂解三氯乙氧羰基（Troc）的新方法。将该方法应用于固相合成，利用邻基参与效应，实现了Troc基在固体载体上的立体控制β-氨基葡萄糖化。以4,6- o -苄基甘露糖基n -苯基三氟乙酸乙酯为糖基供体，TMSOTf为酸催化剂（α:β=1:9），实现了立体选择性β-甘露糖基化。我们还以n -邻苯甲酰唾液酸苯三氟乙酸酯为供体，TMSOTf为酸性催化剂，建立了α-选择性唾液酰化反应。我们之前报道了基于亲和分离（SAS）的合成，其中具有标签片段的所需化合物通过使用标签和识别标签的分子之间的特定亲和性从反应混合物中快速分离出来。在本研究中，我们利用豆荚醚标签与固体负载铵离子的相互作用，开发了新的SAS方法。将本方法应用于Lewis x等小寡糖文库的快速合成，合成了免疫刺激糖缀合脂多糖和肽聚糖的不同部分结构和类似物，以阐明其生物学功能。

Efficient synthesis of oligosaccharides by using solid-phase method and hybrid method of solid-phase and liquid-phase was investigated. We previously established "Chemical Fishing" method, where desired compound having azide function is selectively fished out of the reaction mixture by using the specific reaction between solid-supported phosphine and azide. This method was applied to the solid-phase synthesis of the elicitor pentasaccharide. Synthetic study of N-linked oligosaccharide of glycoprotein was also investigated. We developed a novel method for cleavage of trichloroethoxycarbonyl(Troc) group by radical reaction using (Bu_3Sn)_2. This method was then applied to solid-phase synthesis and rendered the use of Troc group for stereocontrolled β-glucosaminilation on solid-support by using its neighboring group participation effect. Stereoselective β-mannosylation was effected by using 4,6-O-benzylidene mannnosyl N-phenyltrifluoroacetimidate as a glycosyl donor and TMSOTf as an acid catalyst(α:β=1:9). We also established α-selective sialylation by using N-phthaloyl sialic acid phenyltrifluoroacetimidate as a donor and TMSOTf as an acid catalyst.We previously reported Synthesis based on affinity separation(SAS), where desired compound having a tag moiety is rapidly separated from a reaction mixture by using specific affinity between the tag and the molecule that recognizes the tag. In the present study, we developed the new SAS method using the interaction between podand ether tag and solid-supported ammonium ion. The present method was applied to the rapid synthesis of small oligosaccharide library including Lewis X. Various partial structures and analogues of immunostimulating glycoconjugate lipopolysaccharide and peptidoglycan were synthesized in order to elucidate their biological functions.