Synthesis and biological activity of ester and ether analogues of α-galactosylceramide (KRN7000)

α-Galactosylceramide (αGalCer, KRN7000) has been identified as a modulator of immunological processes through its capacity to bind iNKT cells mediated by CD1d molecules. Some analogues in while the amide group in αGalCer is replaced with ester or ether groups were synthesized from d-arabinitol or l-ribose to evaluate their ability to activate iNKT cells. Ester analogues 30a, 31a, and 61 showed activity for IFNγ and IL-4 production of iNKT cells, while ether (31b) and 4-methoxy ester (76) analogues of α-galactosylceramide were not active for iNKT cells.

Graphical abstractThese three ester analogues showed activity for IFNγ, and IL-4 production of iNKT cells.Figure optionsDownload full-size imageDownload as PowerPoint slide