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Although mannose\u2010 and fucose\u2010based ligands have received considerable attention, Lewis\u2010based inhibitors remain relatively underexplored. In this study, we report the first synthesis of Lewis\u2010X\u2010containing 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\u2010X\u2010containing triterpenoid saponins are among the most potent monovalent inhibitors reported to date of DC\u2010SIGN\u2010 and L\u2010SIGN\u2010mediated transfer of HIV\u20101 infection to CD4\u2010positive cells, with IC<jats:sub>50<\/jats:sub>\u00a0values in the low micromolar range (21\u201350 \u00b5M). 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