Synthesis and evaluation of human T cell stimulating activity of an α-sulfatide analogue

A concise synthesis of α-sulfatide 1, an analogue of natural glycolipid antigens with potential anti-tumor activity, was performed. Two different approaches to the α-glycosidic bond were explored, resulting in a high yield and excellent stereoselectivity. Compound 1 combines the structural features of sulfated β-GalCer (sulfatide) and α-GalCer, which activate specific T cells. α-Sulfatide 1 was stimulatory for CD1d-restricted semi-invariant Natural Killer T (iNKT) cell clones, although less potent than α-GalCer, while it was not recognized by CD1a-restricted sulfatide-specific T cells.