- 學位論文
立體選擇性醣基化反應之方法開發
Development of Methodologies for Stereoselective Glycosylation
摘要
2-脫氧醣分子基團存在於許多具生物活性的天然物結構中。在本論文的第一部分，描述了一個於無溶劑的條件下使用烯醣（glycal）簡單制備硫-和氧-2-脫氧醣苷分子的方法。於無溶劑環境中使用等當量之三甲基溴硅烷（TMSBr）調控硫化加成醣基化反應，得到一系列高產率的硫-2-脫氧醣苷衍生物，並且沒有產生常見的Ferrier重排副產物。此外於烯醣和親核受體的偶合反應中添加三甲基溴硅烷和三苯基氧化磷（TPPO）可以促使反應生成出各種高α-選擇性 （10:1）和良好產率的氧-2-脫氧醣苷衍生物。 ㄧ般制備醣苷鍵的策略通常包括三個步驟：（i）將一號位置碳上的羥基轉化為良好的離去基團，（ii）活化離去基團，和（iii）與親核試劑進行偶合反應。本篇論文的第二部分提出了一種環保並且可以直接活化羥基進而制備各種氧-醣苷衍生物的方法，研究中發現二苯基三氟甲磺酸銨（DPAT）是脫水糖基化反應的首選催化劑，催化一系列的武裝（armed）、解除武裝（disarmed）及2-脫氧的醣供體，生成高產率的醣苷化合物（高達99%）。此外我們發現到催化劑的氮-芳基團可以維持反應中的疏水環境，將醣基化反應中產生等當量的水分子排出反應中心，因此不需要添加乾燥劑驅使反應完成。在一系列制備雙醣、醣基氨基酸和其他醣共軛體的合成中證明了該方法的普遍性和多功能性。
並列摘要
2-Deoxyglycosides are vital components in numerous bioactive products. In the first part of this thesis, a simple and solvent-free method using glycals for preparation of 2-deoxyglycosides from glycals is described. Addition of p-thiocresol onto glycals was promoted by a stoichiometric amount of trimethylsilyl bromide (TMSBr) in neat conditions to generate S-2-deoxyglycosides in good to high yields. Undesired Ferrier rearrangement products were not observed under the reaction conditions. Furthermore, a combination of TMSBr and triphenylphosphine oxide (TPPO) enables the coupling reactions between glycals and acceptors to give a variety of O-2-deoxyglycosides in good to excellent yields with high α-selectivity (up to 10:1). The strategies for formation of glycosidic bonds usually comprise three steps: (i) conversion of anomeric hydroxyl group into a good leaving group, (ii) activation of the leaving group, and (iii) coupling reaction with incoming nucleophile. Without prior elaboration of anomeric hydroxyl group, a straightforward and environmental-friendly method for synthesis of various O-glycosides is demonstrated in the second part of this thesis. Diphenylammonium triflate (DPAT) was found to be the catalyst of choice for dehydrative glycosylation. The DPAT-catalyzed dehydrative glycosylations were carried out with a series of glycosyl donors, including armed, disarmed and 2-deoxyglycoses, to give the corresponding glycosides in good to high yields (up to 90%). As the N-aryl groups of DPAT can create a hydrophobic environment, the water molecule generated during the glycosylation would be expelled from the reaction center, and thus no external drying agent is needed to drive the reaction to completion. The generality and versatility of this method were demonstrated in the synthesis of a series of disaccharides, glycosylated amino acids, and other glycoconjugates.
參考文獻
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