Synthesis and structure-activity relationship study of cytotoxic lupane-type 3 beta-O-monodesmosidic saponins with an extended C-28 side chain

0429932 - ÚEB 2015 RIV GB eng J - Journal Article
Cmoch, P. - Korda, A. - Rárová, Lucie - Oklešťková, Jana - Strnad, Miroslav - Luboradzki, R. - Pakulski, Z.
Synthesis and structure-activity relationship study of cytotoxic lupane-type 3 beta-O-monodesmosidic saponins with an extended C-28 side chain.
Tetrahedron. Roč. 70, č. 17 (2014), s. 2717-2730. ISSN 0040-4020. E-ISSN 1464-5416
R&D Projects: GA MŠMT(CZ) LO1204
Institutional support: RVO:61389030
Keywords : BETULIN DERIVATIVES * SECONDARY ALCOHOLS * ANTITUMOR-ACTIVITY
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 2.641, year: 2014

A concise synthesis of lupane triterpenes with an elongated carbon chain at the C-28 position, as well as saponins containing D-mannose, L-arabinose, and L-rhamnose moieties at the C-3 position is described. The overall synthesis of the new triterpenes involved seven linear steps starting from natural betulin: selective protection of a hydroxyl group, oxidation, elongation of the carbon chain by Grignard reaction, and deoxygenation. O-Glycosides were obtained by glycosylation of triterpenes with classical Schmidt's donors. Additionally, all new compounds were evaluated in vitro for their cytotoxic activities. Several triterpenes and the corresponding saponins exhibited an interesting cytotoxic activity profile against human cancer cell lines. The therapeutical index of active triterpenes is very high, since almost none of them were cytotoxic for normal BJ fibroblasts. These results open the way to the synthesis of various lupane-type saponin derivatives as potentially bioactive compounds.
Permanent Link: http://hdl.handle.net/11104/0234895