The total synthesis of 4,5-cis unsaturated alpha-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 alpha-stereoselectivity was achieved in good yield (67%). With regard to the therapeutic use of alpha-GalCer, the novel analogues (1b and 1c) distinctly induced a Th1-biased cytokine response, avoiding induction of a contradictory response and overstimulation.
National Natural Science Foundation of China 
; International Science & Technology Cooperation Program of China [2010DFA34370]
; International S&T Cooperation Program of Zhejiang [2013C14012]
; Yunnan High-End Technology Professionals Introduction Program [2010CI117]