alpha-半乳糖神經酰胺（alpha-神經酰胺，alpha-GalCer）是已知可以與樹突狀細胞上的CD1d受體進行結合進而活化自然殺手 T細胞，之後促使其分泌T輔助細胞 1（Th1細胞）和Th2細胞激素，分別具有抗感染活性和預防自身免疫性疾病的作用。 alpha-神經酰胺促使這兩種細胞因子的分泌並不具有選擇性，且Th1和Th2細胞因子釋放出的細胞激素會互相抑制使其alpha-神經酰胺促的效力是有所侷限。為了能專一性的刺激免疫反應專一性的釋放出Th1和Th2細胞激素，因此有許多□-神經酰胺衍生物經由不同的策略被合成出來，但一直以來都沒有有效的策略可以做為構造□-神經酰胺分子庫的策略，並藉此快速篩選出有活性的化合物。在此我們提供了一個有效的方法來建構□-神經酰胺之類似物，此方法經由Julia-Kociensky烯烴化反應來引入各種不同的脂質化合物及耦合反應連接各種脂肪酸並藉著可重複使用的氟標的物（Fluorous tag）快速純化分離產物。 引入可回收再利用的氟標的物作為純化的策略可以減少有機溶劑的使用（在氟矽膠管柱層析的過程以混合的甲醇及水分離產物）是較為環保的合成策略符合綠色化學的概念。以此合成策略可以建構出核心化合物77，由起始物D-來蘇糖開始共15步產率4.9％並成功地得到65個□-神經酰胺似物，包含其中KRN7000（98a）。之後會進一步進行這些化合物的活性測試。

Alpha-galactosyl ceramide (alpha-GalCer) has been known to bind to the CD1d receptor on dendritic cells and activate invariant natural killer T (iNKT) cells, which subsequently secrete T-helper-cell 1 (Th1) and Th2 cytokines, which correlate with anti-infection activity and the prevention of autoimmune diseases, respectively. alpha-GalCer elicits the secretion of these two cytokines nonselectively, and thus, its effectiveness is limited by the opposing effects of the Th1 and Th2 cytokines. Therefore there were many alpha-GalCer derivatives syntheized by different strategy for specific releasing Th1 or Th2 cytokines by immune respone, but ultimately no effective approach could construct □-GalCer library for rapid screening. Herein we provided a effectively method to construction of the □-GalCer analogues via Julia-Kociensky olefination induced various lipid chains and coupling reaction connected with various fatty acids and it can be purified effectively by reusable Ftag. This strategy reduced the waste of organic solvent (elute with methanol/water during FSPE) in accordance the concept of green chemistry. The core building block 77 was obtained in 4.9% yield from commerically available D-lyxose and we successfully obtained 65 alpha-GalCer analogues contained 98a (KRN7000) by using this approach. The activity of these compounds will be carried out in the future.

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