We have synthesized a number of Quillaja saponaria Molina (QS) saponin analogues with a different C28 sugar unit, which features either 3,4-diacetyl groups or a 3,4-cyclic carbonate group at the reducing end fucoside to mimic the naturally occurring saponin adjuvant QS-7. Immunological evaluations of these analogues in BALB/c mice indicate that truncating the C28 oligosaccharide of the natural product to the tetrasaccharide (as in 5d (β)) could retain the adjuvant's activity in enhancing IgG1 and IgG2a productions, albeit the activity is lower than that of QS-21. Further truncation or changing stereochemistry of glycosidic linkage between the tetrasaccharide and the triterpenoid quillaic acid (QA) core or within the tetrasaccharide eliminated the saponins' adjuvant activity in terms of IgG production. On the other hand, increasing resemblance to QS-7 increased adjuvant activity and led to saponin 3's similar IgG1 and IgG2a activities to QS-21's, indicating that the unique adjuvant activities of QS saponins are determined by their specific structures.