迭代外源親核性基調控1,2-順式醣基化反應及其應用

Abstract

醣類是含量最多生化分子，已被證實能參與許多重要的生化反應，例如細胞貼附與辨識、受體活化與胞噬作用，也因此增加了合成醣類的需求以研究其在醫藥或生化領域上的功能與應用。 醣類合成中最困難的便是立體選擇性的控制，其中又以1,2-順式選擇性最為困難，雖然目前已經有很多方法致力於1,2-順式醣苷鍵的選擇性合成，但多為利用特殊的保護基來達到立體選擇性的調控，但在醣分子上引進與移除這些保護基是很費時的。 我們建立了一套新的合成方法，用以合成1,2-順式醣苷鍵，我們以穩定的硫醣作為醣予體，在反應過程中即時生成 (in situ formation)具有1,2-順式選擇性的碘醣予體 (glycosyl iodide)，由於反應過程沒有牽涉到保護基的使用，故為較省時的合成方法。而我們也將此方法應用於合成Acinetobacter haemolyticus的多醣體片段與幽門桿菌的固醇醣苷 (steryl glycoside)類似物。

Carbohydrates are mostly abundant biomolecules and server many important functions. It participates in many biological processes, such as cell adhesion, cell recognition, receptor activation, and endocytosis. 1,2-cis Glycosides remain an obstacle in glycosynthesis. Much effort has been dedicated to developing 1,2-cis stereoselective glycosylation methods but most of them involved in protecting group manipulation. However, the removal and introduction of these unconventional protecting groups are laborious. Herein we report a novel iterative modulation approach by combining the use of N-formylmorpholine (NFM) and tetrabutylammonium iodide (TBAI) to provide a mild and convenient entry for α-glycosyl iodides which are already known to be able to afford high 1,2 cis-selectivity. We also extended this method to synthesis the inner core fragments of Acinetobacter haemolyticus and analogues of steryl glycoside form Helicobacter pylori.