The present disclosure encompasses QS-21-based structurally-defined adjuvants to address the need for stronger, safer, and easier-to-access adjuvants. The new compositions can provide tools for addressing long-standing mechanistic questions concerning saponin immune-potentiation through structure-activity-relationship (SAR) studies. Most advantageously, the compounds of the disclosure may be formulated into pharmaceutically acceptable compositions, including vaccines that may be delivered to a subject human or animal subject. The compounds can then act as, for example, an adjuvant to augment an immunological response to a vaccine immunogen.