具特殊穩定性的甲基砒碇保護基之三甲基矽基醣苷分子用於合成多樣立體結構之1,1’-雙醣及其應用

Abstract

這本論文共包含了兩個章節。第一章節介紹了自然界中含有1,1'- 醣苷鍵的寡醣化合物以及如何利用不對稱化反應和1,1'-醣基化反應 來製備它們。雖然目前已經存在許多已知方法來製備1,1'-醣苷化合物，我們仍缺乏一個有效的方法來合成多樣的不對稱1,1'-雙醣。

有鑑於此，我們對於1,1'-醣基化反應進行了相關的研究。我們使 用的合成策略結合了利用立體引導的醣予體及立體組態穩定的甲基 砒啶保護三甲基矽基醣受體。甲基砒啶在醣基化反應中所扮演的角色 及其穩定醣受體的能力在結構及選擇性的研究和NMR實驗中被驗證。 接著我們進一步開發了具有高立體選擇性的三甲基矽基化反應於醣 受體。然後藉由結合不同的醣予體及受體，我們有系統地建構了αα, αβ, βα 及 ββ 的1,1'-醣苷鍵。

在第二章節中，我們注重在合成海藻醣胺及胺基醣苷抗生素的類似 物。結合了在第一章節所開發的1,1'-醣基化反應以及官能基的修飾， 疊氮保護1,1'-雙醣可以高選擇性地被合成出來。經由去保護及疊氮還 原反應後，我們合成出了一系列的海藻醣胺天然物及胺基醣苷的類似 物作為未來的生物活性研究。

This thesis consists of two chapters. Chapter 1 describes the background introduction of the oligosaccharides with 1,1'-linkage and their preparation through the desymmetrization and 1,1'-glycosylation methods. Although numerous methods have been developed, an efficient way for the diverse synthesis of non-symmetrical 1,1'-disaccharides was still absent.

The development of 1,1'-glycosylation method is described. Our strategy features the joint force of stereodirecting glycosyl donor and configurationally stable Pico protected TMS glucoside acceptor. The role of picoloyl group and its conferred stability to the TMS glucoside acceptor was vertified through the structure-selectivity relationship study and NMR study. We developed highly stereocontrolled methods for the preparation of TMS glucoside acceptors. Then, we present systematic constructions of αα, αβ, βα and ββ 1,1'-glycosidic bonds with multiple examples in high stereoselectivity and satisfactory yield.

Chapter 2 focuses on the synthesis of trehalosamine and aminotglycoside analogues. Based on our 1,1'-glycosylation method described in Chapter 1 and the functional group modifications, we synthesized a small library of azido protected 1,1'-disaccharides with good stereocontrol. The fully deprotection and azido reduction of 1,1'-disaccharides furnished the natural 2-, 3-, 4-, and 6-trehalosamine and non-symmetrical aminoglycoside analogues for the future bactericidal studies.