Abstract
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.