研究新單磷酸耦合反應以合成醣二磷酸酯

Study of Sugar Diphosphate Formation via New Monophosphate Coupling Reactions

林騰起(Teng-Chi Lin)

指導教授 ： 方俊民

國立臺灣大學/理學院/化學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.02304

摘要

雙磷酸在生物體內扮演不可或缺的角色，以寡糖的生合成為例:生物體利用醣基轉移酶催化核苷酸醣和醣基受體形成一個新的醣苷鍵。在細菌細胞壁的生合成中，雙磷酸亦為構成Lipid I及Lipid II的重要部分。現今已知建構雙磷酸的步驟往往繁瑣且反應時間冗長，而偏低的產率更為阻礙合成核苷酸糖以及Lipid II衍生物的主要原因，因此，研究發展更有效率的雙磷酸合成方法是勢在必行。
我們發現2,4,6-三異丙基苯磺醯氯(2,4,6-triisopropylbenzenesulfonyl chloride)以及 2,4,6-三氯-1,3,5-三氮代苯(2,4,6-trichloro-1,3,5-triazine, cyanuric chloride)為合適建構雙磷酸之試劑，同時藉由添加溴化鎂作為螯合試劑以拉近兩單磷酸之距離進而增加了反應的效率。在我們模型反應中反應時間為5–48小時，轉換效率則為20–70%不等。另外我們也利用2,4,6-三異丙基苯磺醯氯合成了GDP-pyrrolidine類似物，並經由比較發現使用 2,4,6-三異丙基苯磺醯氯較傳統使用預先製備之morpholidate來的更有效率，這樣的策略為合成雙磷酸化合物提供了另一種選擇。

關鍵字

雙磷酸

並列摘要

Diphosphate is an indispensible starting material in organism. For example, oligosaccharides are synthesized from a sugar nucleoside diphosphate and a glycosyl acceptor by glycosyltransferases. Diphosphate moiety is also an important part in the structures of Lipid I and Lipid II in the process of bacterial cell wall formation. The approaches to the sugar nucleoside diphosphate and analogues of Lipid II are impeded by the diphosphate bond formation, which often requires tedious procedure and long reaction time, albeit in low yield. So, exploration of efficient methods to get diphosphate compounds is needed.
We found that 2,4,6-triisopropylbenzenesulfonyl chloride and 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride) were proper condensation reagents for diphosphate bond construction. By using MgBr2 as the chelating agent of the two monophosphate substrates, the coupling reactions proceeded efficiently. The reaction times are 5–48 hours to give conversion yields of 20–70% in our model reactions. We synthesized the GDP-pyrrolidine analogue, and found that using 2,4,6-triisopropylbenzenesulfonyl chloride is more efficient than the conventional method using morpholidate. This approach provides an alternative choice for diophosphate formation.

並列關鍵字

diphosphate

參考文獻

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