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

• Main Authors: Arockiya Samy Abragam Joseph, 亞洛克
• Other Authors: Lin, Chun-Cheng
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/36201059773576841364

博士 === 國立清華大學 === 化學系 === 103 === 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.