Synthesis of Rhamnose‐Modified Lewis‐X‐Containing Saponins

Abstract

We report the synthesis of betulinic acid and echinocystic acid saponins featuring an unnatural analogue of the Lewis‐X trisaccharide, in which the l‐fucose residue is replaced by l‐rhamnose. These triterpenoid saponins were designed as negative controls for dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing non‐integrin (DC‐SIGN)‐targeted antiviral and immunological studies. The target saponins were synthesized using both iterative and convergent strategies, requiring nine and six steps, respectively, for the longest linear sequence starting from allyl betulinate and allyl echinocystate. Glycosylation reactions were performed using trihalogenoacetimidate and thioglycoside donors, which provided excellent yields and complete control over stereoselectivity. This work establishes a robust foundation for the synthesis of lupane‐ and oleanane‐type triterpenoid saponins incorporating Lewis‐X trisaccharide analogues.