4,5-cis unsaturated α-GalCer analogues distinctly lead to CD1d-mediated Th1-biased NKT cell responses

The total synthesis of 4,5-cis unsaturated α-GalCer analogues was achieved, and their immune-response altering activity was assessed in vitro as well as in vivo in mice. Using glycosyl iodide as a glycosyl donor, construction of the sphingosine unit was shortened by four steps and single α-stereoselectivity was achieved in good yield (67%). With regard to the therapeutic use of α-GalCer, the novel analogues (1b and 1c) distinctly induced a Th1-biased cytokine response, avoiding induction of a contradictory response and overstimulation.