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In pursuit of cytotoxic triterpenoids. Functionalization of lupane, taraxastane, friedelane, and baccharane derivatives via oxidation with selenium reagents

K. Kuczynska, P. Cmoch, L. Rárová, J. Jaźwiński, A. Korda, JW. Morzycki, M. Kvasnicová, K. Gwardiak, R. Karczewski, M. Yaghoobi Anzabi, R. Luboradzki, M. Strnad, Z. Pakulski

. 2025 ; 295 (-) : 117770. [pub] 20250519

Jazyk angličtina Země Francie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25015085

A series of triterpenoids of the lupane, taraxastane, friedelane and baccharane type were oxidized using selenium dioxide (SeO2) and benzeneseleninic anhydride (BSA) under various conditions. Depending on the reaction conditions, different reaction pathways were observed, including dehydrogenation, allylic oxidation, and 1,2-diketone formation. In this way, derivatives functionalized in the triterpene core (especially in rings A, D, and E), difficult to obtain by other methods, can be easily prepared. In some cases, rarely observed α-phenylseleno-ketones were isolated. An unexpected reaction involving the cleavage of the carbon-carbon double bond was observed in the presence of stoichiometric amounts of osmium tetroxide. Further transformations of selected intermediates facilitated the synthesis of new, functionally enriched derivatives. The key reaction pathways were investigated using density functional theory (DFT), focusing on bond length variations and transition states, revealing energetically favored pathways and critical transition structures, including covalent and noncovalent interactions. Solvent and isomerization equilibrium effects were proposed to explain the experimentally observed discrepancies. Cytotoxic activity of selected derivatives was investigated. Derivatives 4 and 38 showed strongest cytotoxicity in cancer cells and fibroblasts (IC50 2.6-26.4 μM); some compounds were selective for G-361 or HeLa cells. These results suggest that they may find application in pharmaceuticals.

Citace poskytuje Crossref.org

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$a A series of triterpenoids of the lupane, taraxastane, friedelane and baccharane type were oxidized using selenium dioxide (SeO2) and benzeneseleninic anhydride (BSA) under various conditions. Depending on the reaction conditions, different reaction pathways were observed, including dehydrogenation, allylic oxidation, and 1,2-diketone formation. In this way, derivatives functionalized in the triterpene core (especially in rings A, D, and E), difficult to obtain by other methods, can be easily prepared. In some cases, rarely observed α-phenylseleno-ketones were isolated. An unexpected reaction involving the cleavage of the carbon-carbon double bond was observed in the presence of stoichiometric amounts of osmium tetroxide. Further transformations of selected intermediates facilitated the synthesis of new, functionally enriched derivatives. The key reaction pathways were investigated using density functional theory (DFT), focusing on bond length variations and transition states, revealing energetically favored pathways and critical transition structures, including covalent and noncovalent interactions. Solvent and isomerization equilibrium effects were proposed to explain the experimentally observed discrepancies. Cytotoxic activity of selected derivatives was investigated. Derivatives 4 and 38 showed strongest cytotoxicity in cancer cells and fibroblasts (IC50 2.6-26.4 μM); some compounds were selective for G-361 or HeLa cells. These results suggest that they may find application in pharmaceuticals.
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$a Cmoch, Piotr $u Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland
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$a Rárová, Lucie $u Laboratory of Growth Regulators, Faculty of Science, Palacký University, and Institute of Experimental Botany, Czech Academy of Sciences, Šlechtitelů 27, CZ-77900, Olomouc, Czech Republic. Electronic address: lucie.rarova@upol.cz
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$a Jaźwiński, Jarosław $u Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland
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$a Morzycki, Jacek W $u Department of Organic Chemistry, Faculty of Chemistry, University of Bialystok, K. Ciołkowskiego 1 K, 15-245, Białystok, Poland
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$a Kvasnicová, Marie $u Laboratory of Growth Regulators, Faculty of Science, Palacký University, and Institute of Experimental Botany, Czech Academy of Sciences, Šlechtitelů 27, CZ-77900, Olomouc, Czech Republic; Department of Experimental Biology, Faculty of Science, Palacký University, Šlechtitelů 27, CZ-77900, Olomouc, Czech Republic
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$a Pakulski, Zbigniew $u Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland. Electronic address: zbigniew.pakulski@icho.edu.pl
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