Synthesis of 6"-triazole-substituted α-GalCer analogues as potent iNKT cell stimulating ligands.

Nora Pauwels, Sandrine Aspeslagh, Dirk Elewaut, Serge Van Calenbergh

Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.

Bioorganic & medicinal chemistry 2012 Dec 15

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We report the synthesis of a small series of 6"-triazol-1-yl-substituted α-GalCer analogues by late-stage conversion of the 6"-OH to an azide group, copper-catalyzed azide-alkyne cycloaddition and final deprotection. When evaluated for their capacity to induce IL-2 secretion in vitro, all compounds proved equally potent or superior to α-GalCer. The S.A.R suggests that the improved antigenic activity is mainly triggered by the triazole functionalization in se. While the introduction of selected substitutuents at C-4 of this heterocyclic ring is tolerated, this generally fails to further improve antigenicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Nora Pauwels, Sandrine Aspeslagh, Dirk Elewaut, Serge Van Calenbergh. Synthesis of 6"-triazole-substituted α-GalCer analogues as potent iNKT cell stimulating ligands. Bioorganic & medicinal chemistry. 2012 Dec 15;20(24):7149-54