The search for safer and more effective vaccine adjuvants has intensified in recent years, with triterpenoid saponins like QS‐21 and its analogues emerging as promising candidates. We report the synthesis of a novel QS‐21 analogue featuring betulinic acid as aglycone, a lupane‐type triterpenoid with low toxicity derived from white birch bark. Two convergent synthetic routes, involving different protecting groups and glycosyl donors (bromide and trichloroacetimidate), were optimized to construct the QS‐21‐based linear trisaccharide motif critical for adjuvant activity. This strategy also enabled efficient preparation of the structurally similar echinocystic acid analogue reported by Gin. The immunological and toxicological profiles of these chimeric saponins, along with Lewis‐X‐containing and rhamnose‐modified derivatives, were evaluated in C57BL/6 wild‐type and hDC‐SIGN transgenic mice. While the synthetic saponins exhibited low toxicity in vitro and in vivo, replacing echinocystic acid with betulinic acid reduced immunogenicity when tested with ovalbumin as a model antigen compared to alhydrogel and QS‐21. These findings provide a foundation for developing saponin‐based adjuvants and demonstrate the utility of advanced glycosylation strategies for synthesizing complex unnatural triterpenoid saponins.

Sialic acid (SA) on the surface of cells is indispensable in numerous physiological and pathological processes, and sensitive and reproducible detection of SA is crucial for diagnosis and therapy in many diseases. Here, we developed a tri-functional nanoprobe as a sensitive and straightforward surface-enhanced Raman spectroscopy (SERS) nanoprobe for sialoglycan detection on cell surfaces. The reporter was designed to provide three key functionalities that make it ideal for SA detection. First, we employed two recognition groups, phenylboronic acid and an ammonium group, that enhance SA recognition and capture efficiency. Second, we used cyano as the Raman reporter because it emits in the cellular Raman silent region. Finally, thiol acted as an anchoring agent to conjugate the reporter to silver nanocubes to provide SERS enhancement. Our molecular nanoprobe design demonstrated the ability to detect SA on the cell surface with high sensitivity and spatial resolution, opening up new routes to cellular diagnostics.

Blocking dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing nonintegrin (DC‐SIGN)‐ and liver/lymph node‐specific intercellular adhesion molecule‐3‐grabbing integrin (L‐SIGN)‐mediated human immunodeficiency virus 1 (HIV‐1) attachment to immune cells represents a promising strategy for developing antiretroviral agents effective during the early stages of sexual transmission. Although mannose‐ and fucose‐based ligands have received considerable attention, Lewis‐based inhibitors remain relatively underexplored. In this study, we report the first synthesis of Lewis‐X‐containing triterpenoid saponins featuring betulinic acid and echinocystic acid as aglycones. These saponins were stereoselectively and efficiently synthesized in six linear steps using a convergent approach that leveraged thioglycoside and trichloroacetimidate glycosylation chemistries. Notably, our findings demonstrate that these Lewis‐X‐containing triterpenoid saponins are among the most potent monovalent inhibitors reported to date of DC‐SIGN‐ and L‐SIGN‐mediated transfer of HIV‐1 infection to CD4‐positive cells, with IC₅₀ values in the low micromolar range (21–50 µM). This work lays a valuable foundation for the development of saponin‐based antiviral agents targeting immune cells.

Marine polysaccharides, including β3-xylan and mixed-linkage xylan (MLX), play a central role in the ocean's carbon cycle. Using an optimized xylose donor, automated glycan assembly enabled the synthesis of β3- and MLX-oligosaccharides up to decasaccharides. Interrogation of these structurally defined substrates with the marine xylanases Xyl4, AlXyn26A, and MfXyn26A revealed a surprisingly broad substrate scope of MLXases toward both β3-xylan and MLX motifs, highlighting AGA-derived glycans as powerful probes for studying marine polysaccharide metabolism.

Oxazoline-based iterative glycosylation to synthesize hexa- and octasaccharides in an expeditious manner.