Synthesis of C6′′-modified α-C-GalCer analogues as mouse and human iNKT cell agonists

Abstract

α-GalCer analogues that combine known Th1 polarizing C6′′-modifications with a C-glycosidic linkage were synthesized. We employed a protecting group strategy that allowed the preparation of both saturated and unsaturated derivatives with variable C6′′-substituents. Selected analogues demonstrate promising activity in mice. Interestingly, the introduction of a 6′′-O-pyridinylcarbamoyl substituent to α-C-GalCer restores its antigenicity in human iNKT cells.