簡潔的製備 D-glycero-alpha-D-talo-octulosonic acid及其醣基化反應

Abstract

這篇論文包含了，（一）方便且簡短的 D -glycero-- D -talo-octulosonic acid (Ko) 以及 Ko 醣予體的合成路徑，和（二）發展了以此新的醣予體的醣基化反應以合 成含 Ko 與 2-keto-3-deoxy- D -manno-octulosonic acid (Kdo)的醣苷。 Ko 酮醣的製備由易得的甘露五環醣，歷經五個簡單的合成步驟得到我們的 目標產物，總產率 50 %。其合成步驟包含了（1）藉由甘露五環醣及乙炔碳陰離 子合成子延長碳鏈到八個碳，（2）藉由氧化末端炔合成alpha-keto ester，以及（3） 去保護及合環反應。其中，關鍵步驟在乙炔碳陰離子合成子的立體選擇幾乎得到 欲得的立體異構物 在我的論文第二部分是利用上述得到的 Ko 醣轉變成醣予體，此醣予體可用 來 Ko 和 Kdo 醣苷的合成。在這一方面，我們發展了一個對於 Ko 的雙功能的保 護基團。醣基化後所得的 Ko 醣苷可以轉變成相對應的 Kdo 醣苷。

This thesis describes (i) development of a convenient and short synthetic route for preparation of D -glycero-- D -talo-octulosonic acid (Ko) and Ko glycosyl donor; and (ii) development of new Ko and 2-keto-3-deoxy- D -manno-octulosonic acid (Kdo) glycoside donor for glycosylation. The synthesis of Ko keto sugar started with readily available mannofuranose, which undergoes a concise five steps conversion to give the target in 50 % overall yield. My synthetic plan involved (i) chain elongation of mannose with an ethynyl carbanion synthon; (ii) alpha-keto ester formation from oxidative of a terminal alkyne; and (iii) deprotection and cyclization. The key step in the synthesis is the stereoselective addition of the ethynyl carbanion synthon, which gave the desired stereoisomer almost exclusively. In the second part of my thesis, the aforementioned Ko sugar was converted to a glycoside donor that could be used for Ko and Kdo glycoside preparation. In this regard, we developed a bi-functional protecting group for the Ko substrate. The resulting Ko glycoside could be transformed into Kdo glycoside.