1,2-順式 α-醣基化策略之應用：(甲)合成寡糖與 (乙)幽門螺旋桿菌之固醇醣代謝物

Abstract

我們利用內加成轉化( in situ adduct transformation ) 為基礎的1,2-順式α-醣基化策略進行合成，此方法的特色是利用醣基亞胺吡啶加合物和糖基碘加合物進行轉換，且使用具穩定性的硫醣作為醣予體，可廣泛應用於合成1,2-順式α-醣苷鍵，不需要特殊保護基即可獲得立體選擇性，我們應用此策略在合成寡醣以及幽門螺旋桿菌的膽固醇醣苷上。

世界上超過 50％ 的人口在其消化道上感染幽門螺桿菌，且幽門螺旋桿菌會吸收來自宿主細胞的膽固醇和脂肪酸或磷脂酸形成膽固醇α-葡萄糖苷衍生物( CGds ) ，目前只知它可能與十二指腸潰瘍與胃癌有所相關，我們想更進一步了解此化合物在人體中的影響，因此需要高純度的CGds來進行一系列的生物測試，但直接從生物體內分離純化有一定的困難度，所以我們利用合成的方式取得。 CGds主要可分為Cholesteryl 6-O-Acyl α-Glucosides ( CAGs ) 與 Cholesteryl 6-O-Phosphatidyl α-Glucosides ( CPGs ) 兩種，我們利用不同長度的飽和脂肪鏈及不飽和脂肪鏈進行合成，藉此來討論 CAGs 對宿主細胞之影響。

A flexible 1,2-cis α-selective glycosylation strategy for a wide range of glycosyl donors and acceptors has been developed, which is based on an in situ adduct transformation protocol. The method features the in situ interconversion of the glycosyl imidinium adduct and glycosyl iodide adduct. We use the strategy to synthesis of oligosaccharides and CAG from Helicobacter pylori.

More than 50％ of the global population are the carriers of Heliobacter pylori. Heliobacter pylori inhabits in stomach epithelium and obtains cholesterol, fatty acids, and phospholipids from host cells. The absorbed metabolites are modified by the bacteria to cholesteryl α-glucoside ( CGs ), which are further elaborated to cholesteryl 6-O-acyl α-glucosides ( CAGs ) and cholesteryl 6-O-phosphatidyl α-glucosides ( CPGs ). Various clinical studies indicate a strong correlation between CGs (and their derivatives) and duodenal ulcers or stomach cancer. We sought to study the relationship between CAGs of different structures and relevant bioactivities of Heliobacter pylori. Based on the method, a panel of CAGs are prepared. They have fatty acids with different chain length and with different number of double bonds.