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Advances in the synthesis and pharmacological activity of lupane-type triterpenoid saponins

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Abstract

Lupeol, betulin and betulinic acid are members of the so-called lupane-type triterpenoids. These natural products found worldwide in quite of lot of vegetables, fruits and plant species exhibit promising pharmacological activities including anti-inflammatory, anti-HIV and antitumor activities. Nevertheless, the poor pharmacokinetic properties of these cholesterol-like triterpenoids hampered further pharmaceutical developments. The synthesis of lupane-type saponins, i.e., sugar-derived lupanes, seems to be a good avenue to improve both their water solubility and pharmacological activity. The aims of this review are twofold: first, to describe the biological activity of naturally occurring lupane-type saponins, and second, report the different methodologies employed for the elaboration of glycosidic linkages at the C-3 and/or C-28 positions on the lupane core. The synthesis of both natural and unnatural lupane-type saponins is discussed with an emphasis on molecules exhibiting relevant biological activities.

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Abbreviations

A549:

Human lung carcinoma

Ara:

α-l-Arabinopyranose

BF3·OEt2 :

Boron trifluoride diethyletherate

CGTase:

Cyclodextrin glycosyltransferase

d-Ara:

α-d-Arabinopyranose

DLD-1:

Human colorectal adenocarcinoma

Gal:

β-d-Galactopyranose

Glc:

β-d-Glucopyranose

HIV:

Human immunodeficiency virus

IC50 :

Half maximal inhibitory concentration

Man:

α-d-Mannopyranose

PMT:

Prodrug monotherapy

Rha:

α-l-Rhamnopyranose

SAR:

Structure-activity relationships

TCA:

Trichloroacetimidate

TMSOTf:

Trimethylsilyl trifluoromethanesulfonate

Xyl:

β-d-Xylopyranose

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Acknowledgments

The authors wish to thank Dr. Yves Janin for proof-reading this manuscript and the anonymous reviewers for helpful comments and suggestions. The financial support of the Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT, fonds forestier 02) is gratefully acknowledged. C. G. wishes to acknowledge the Programme d’Aide Institutionnel à la Recherche de l’Université du Québec à Chicoutimi (PAIR-UQAC), the Fondation de l’UQAC as well as FQRNT for graduate scholarships.

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  1. Laboratoire LASEVE, Chaire de Recherche sur les Agents Anticancéreux d’Origine Naturelle, Département des Sciences Fondamentales, Université du Québec à Chicoutimi, 555, boul. de l’Université, Chicoutimi, QC, G7H 2B1, Canada

    Charles Gauthier, Jean Legault, Marianne Piochon-Gauthier & André Pichette

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  1. Charles Gauthier
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  2. Jean Legault
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  3. Marianne Piochon-Gauthier
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  4. André Pichette
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Correspondence to Charles Gauthier or André Pichette.

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Gauthier, C., Legault, J., Piochon-Gauthier, M. et al. Advances in the synthesis and pharmacological activity of lupane-type triterpenoid saponins. Phytochem Rev 10, 521–544 (2011). https://doi.org/10.1007/s11101-010-9176-y

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  • DOI: https://doi.org/10.1007/s11101-010-9176-y

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