Acid-Catalyzed E-Ring Expansion and Isomerization of 3-Acetylbetulin: Synthesis of Cytotoxic Anhydrobetulin Saponins

Abstract

22(17 → 28)abeo-Lupene derivatives 5a and 6a were obtained after the acid-catalyzed E-ring expansion of 3-acetylbetulin (1a). Glycosylation of these dehydrated triterpenoids using Schmidt's trichloroacetimidate sugar donors in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) provided the new anhydrobetulin saponins 7b–7e in which the terminal olefin C-20(29) isomerizes to form a C-19 tetrasubstituted alkene. The preliminary cytotoxic evaluation revealed that saponins 7b–7d exhibited a moderate cytotoxic activity against A549, DLD-1, and WS1 human cell lines with IC₅₀ ranging from 22 to 49 μM.

Keywords:

• Acid-catalyzed isomerization
• anhydrobetulin saponins
• betulin
• cytotoxicity
• E-ring expansion
• triterpenoids

ACKNOWLEDGMENTS

The authors kindly thank Catherine Dussault for the biological assays as well as Professor François-Xavier Garneau for reviewing this manuscript. This work was supported by grants from the “Fonds québécois de la recherche sur la nature et les technologies” (FQRNT, fonds forestier 02) and by the “Chaire de recherche sur les agents anticancéreux d'origine naturelle” of the University of Québec at Chicoutimi.

Notes

^a Mean values ± standard deviation for three independent experiments made in triplicate.