壹、Meiothermus taiwanensis ATCC BAA-400 醣脂質衍生物之全合成研究 貳、立體選擇性合成半乳醣胺與絲胺酸共軛物

Abstract

本論文分為兩大部分第一部份描述了一個四醣醣脂衍生物的全合成，其模 仿了嗜熱細菌Meiothermus taiwanensis ATCC BAA-400 的核心結構。在我們 的方法中採用了以二甲基甲醯胺控制的預活化醣質反應和低濃度的□選擇 性醣基化方法來分別架構1,2-順式 □□和1,2-反式 □鍵結。而這些四醣結構 中的糖苷鍵透過收斂式[2 + 2]和連續性[1 + 1 + 2]的合成策略成功實現了高 效率和高立體選擇性。本篇論文更是首先體現了此分子的全面性去保護工 作。我們更進一步透過以二甲基甲醯胺控制的預活化醣質反應的條件控制 達成了有極佳選擇性的□-Glc(1→1)-glycerol 結構。 第二部份描述了一個新的對於 □-GalNAc-O-Ser（Tn 抗原）結構的合成 方法。首先，半乳糖胺和絲氨酸基團之連結也受益於DMF 控制的□選擇性 醣質化反應。這種偶合的策略提供了高度選擇性的醣苷鍵形成。其次，我 們開發了更為方便的途徑來選擇性打開6 號位置作進一步的修飾。基於此 結果，我們的實驗室成功地合成了Tn 的三醣衍生物 - F1□□抗原。

This thesis is divided into two parts. Part I describes a total synthesis of a tetrasaccharide derivatives, which simulates the core structure of thermophilic bacteria Meiothermus taiwanensis ATCC BAA-400. In our approach, we employed DMF-modulating glycosylation via pre-activation and low concentration □-selective glycosylation (LCG) methods to construct 1,2-cis □- and 1,2-trans □-glycosidic linkage respectively. Such glycosidic bonds were constructed with high efficiency and satisfactory stereoselectivity. Both the convergent [2 + 2] and sequential [1 + 1 + 2] glycosylation approaches were adopted. Further, the global deprotection of this molecular was demonstrated in this thesis. Moreover, we also synthesized the □-Glc(1→1)-glycerol structure with excellent selective via conditional optimized DMF modulating glycosylation. Part II concerns the development of a new methodology towards □-GalNAc-O-Ser (Tn antigen) structure. First, the □-glycosidic bond between a galactosamine building block and a serine moiety employed the DMF modulating glycosylation. The highly selective glycosidic bond formationswas afforded via this coupling strategy. Second, we developed a more accessible route to selective open the 6-position for further modifications. Based on this result, a trisaccharide Tn derivative (F1□ antigen) was successfully synthesized in our laboratory.