1,1,1,3,3,3-Hexamethyldisilazane (HMDS) Trimethylsilylation of Alcohols for Concise Carbohydrate Synthesis

亞洛克(Arockiya Samy Abragam Joseph)

指導教授 ： 林俊成 ； 王正中

國立清華大學/理學院/化學系/博士(2015年)

摘要

本論文致力於開發一系列具位置選擇性之保護與官能基化的一鍋化合成策略，特別是,-海藻醣的衍生醣脂質。在第一章裡，我們利用三甲矽烷基三氟甲磺酸酯 (TMSOTf) 催化六甲基二矽氮烷 (HMDS) 有效地使醣類完全矽烷基化以利下一步反應，並在沒有酵素試劑的幫助下，對未保護的醣類進行選擇性醋酸化反應。結合此簡單的矽烷基化反應，我們成功於兩步內合成出許多高產率之6-磷酸化碳水化合物，也驚訝地觀察到具位置選擇性之雙醣單磷酸化反應。其中，由於6-磷酸化海藻醣於生物學上、對植物生長的重要性而受到注目。不同於其它醣類，海藻醣為一對稱分子。然而，許多與結核菌毒性有關的海藻醣衍生醣脂質主要為非對稱結構。利用此選擇性磷酸化反應，我們能有效地合成不對稱之海藻醣。

在第二章中，我們也開發了高效率的乙腈催化六甲基二矽氮烷之三甲矽烷基化合成方法，此具有化學選擇性的方法可將羥基三甲矽烷基化並留下氨基，以利接下來對氨基醣之氮原子進行勻相、具化學選擇性的官能基化反應。此合成方法不僅能夠應用在如葡萄糖胺、半乳醣胺、唾液酸等結構單純的氨基醣基質，也適用於結構複雜的氨基醣基質，如新黴素硫酸化物與其它氨基醣分子。應用於6-磷酸化葡萄醣胺的化學合成方法有效地達到在極短的步驟內獲得極佳的總產率。

關鍵字

六甲基二矽氮烷 ； 矽烷基化反應 ； 磷酸化反應 ； 不對稱化海藻醣

並列摘要

This thesis is concern with regioselective one-pot protections and functionalisations of carbohydrates, especially on ,-trehalose-derived glycolipids. In chapter 1, we developed an efficient TMSOTf-catalyzed-HMDS silylation of sugars which can easily lead to subsequent reactions in a one-pot fashion and selective non-enzymatic acetylation reactions directly from unprotected sugar. By incorporating this simple silylation method we synthesized many carbohydrate 6-phosphates easily in 2 steps in excellent yields, and surprisingly we also observed the regioselective mono phosphorylation in disaccharides as well. Among them trehalose 6-phosphate was highlighted, because of its biological importance in plant growth. Apart from that, trehalose is a symmetrical molecule, however, many trehalose based glycolipids are involved in virulence of mycobacterium tuberculosis, but they are majorly unsymmetrical. By utilizing our selective phosphorylation method, we are able to desymmetrize trehalose effectively in chapter 2.
In chapter 3, we describe a highly efficient CH3CN-promoted HMDS trimethylsilylation method that chemoselectively trisilylates hydroxyl groups over the amine groups and enable the subsequent homogenous chemoselective N-functionalisation of amino sugars. This method can not only be applied to simple amino sugar substrates, such as glucosamine, mannosamine, galactosamine and sialic acid, but also multiple amine substrates, like neomycin trisulfate and other amino glycosides. The application to the chemical synthesis of glucosamine 6-phosphate was efficiently achieved in an excellent overall yield in very short steps.

並列關鍵字

HMDS ； Silylation ； Phosphorylation ； Trehalose desymmetrization

參考文獻

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