Synthetic Strategies and Immunological Evaluation of C-Linked α-Galactosylceramide Analogs.

Invariant natural killer T (iNKT) cells recognize lipid antigens, such as α-galactosylceramide (α-GalCer), presented on CD1d, leading to the production of cytokines. C-Glycoside analogs of α-GalCer have garnered attention due to their stability in vivo and their superior therapeutic effects in disease models, including anti-malarial and anti-tumor activity, compared to native α-GalCer. The carbon linkage of C-glycosides is fundamentally inert to glycosyl hydrolases, but the loss of hydrogen-bonding ability and changes in conformational distribution may influence the biological activity. Recent advancements in the synthesis of C-linked α-GalCer have facilitated the creation of new C-glycoside analogs. This review summarizes the evolution of synthetic strategies and the biological activities of the obtained C-linked α-GalCer analogs.