Synthesis and in vivo evaluation of 4-deoxy-4,4-difluoro-KRN7000.
Leung L., Tomassi C., Van Beneden K., Decruy T., Elewaut D., Elliott T., Al-Shamkhani A., Ottensmeier C., Van Calenbergh S., Werner J., Williams T., Linclau B.
The synthesis of 4-deoxy-4,4-difluoro-KRN7000 starting from phytosphingosine is described. Key steps include a regioselective benzylation of azidophytosphingosine and a deoxofluor-mediated fluorination of the corresponding 4-ketone. This fluorination failed completely when the adjacent 3-OH was protected as benzyl ether but proceeded well when a benzoyl group was used. The biological evaluation reveals a bias toward Th1 cytokine induction upon Natural Killer T cell activation.