RCAI-56, a carbocyclic analogue of KRN7000:: its synthesis and potent activity for natural killer (NK) T cells to preferentially produce interferon-γ

RCAI-56 (3), a carbocyclic analogue of KRN7000 (1) was synthesized through an efficient coupling of a carba-alpha-D-galactose derivative 11 with cyclic sulfamidate derivative 13 of phytosphingosine to give 15. Carbasugar derivative 11 was prepared by starting from methyl alpha-D-galactopyrano side (4), employing Pd(II)-catalyzed Ferrier rearrangement as the key step. RCAI-56 (3) is a potent stimulant of NKT cells in vivo to induce the production of Th1 biased cytokines such as interferon-gamma in mice. According to the docking model of CD1d-3 complex, its stabilization energy is approximately at the same level as that of the CD1d-1 complex. (c) 2007 Elsevier Ltd. All rights reserved.