'Click' synthesis of triazole-based spirostan saponin analogs

Abstract

Novel analogs of spirostan saponins in which the glycosidic bond has been replaced by a triazole linkage are described. For this, a direct oligosaccharide-steroid conjugation approach based on the Cu-1-catalyzed azide-alkyne 1,3-dipolar cycloaddition was implemented, leading to diverse combinations of saponin analogs with variations in the trisaccharide moiety, the artificial linkage, and the steroid-skeleton functionalization. This 'click' process proved great efficiency for the ligation of two bulky building blocks (e.g., chacotriose derivatives and spirostanes bearing axial azides), which enabled the rapid creation of a small library of triazole-based analogs for cytotoxicity evaluation. A molecular modeling study was performed to understand the conformational and electronic differences between a natural saponin and its triazole-based analogs.