Three new dihydro-β-agarofuran sesquiterpenes from the seeds of Maytenus boaria

Abstract

As part of a project studying the secondary metabolites extracted from the Chilean flora, we report herein three new β-agarofuran sesquiterpenes, namely (1S,4S,5S,6R,7R,8R,9R,10S)-6-acetoxy-4,9-dihydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepine-5,10-diyl bis(furan-3-carboxylate), CHO, (II), (1S,4S,5S,6R,7R,9S,10S)-6-acetoxy-9-hydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepine-5,10-diyl bis(furan-3-carboxylate), CHO, (III), and (1S,4S,5S,6R,7R,9S,10S)-6-acetoxy-10-(benzoyloxy)-9-hydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepin-5-yl furan-3-carboxylate, CHO, (IV), obtained from the seeds of Maytenus boaria and closely associated with a recently published relative [Paz et al. (2017). Acta Cryst. C73, 451-457]. In the (isomorphic) structures of (II) and (III), the central decalin system is esterified with an acetate group at site 1 and furoate groups at sites 6 and 9, and differ at site 8, with an OH group in (II) and no substituent in (III). This position is also unsubstituted in (IV), with site 6 being occupied by a benzoate group. The chirality of the skeletons is described as 1S,4S,5S,6R,7R,8R,9R,10S in (II) and 1S,4S,5S,6R,7R,9S,10S in (III) and (IV), matching the chirality suggested by NMR studies. This difference in the chirality sequence among the title structures (in spite of the fact that the three skeletons are absolutely isostructural) is due to the differences in the environment of site 8, i.e. OH in (II) and H in (III) and (IV). This diversity in substitution, in turn, is responsible for the differences in the hydrogen-bonding schemes, which is discussed.

Maytenus disticha Extract and an Isolated β-Dihydroagarofuran Induce Mitochondrial Depolarization and Apoptosis in Human Cancer Cells by Increasing Mitochondrial Reactive Oxygen Species

“…Looking for natural anticancer agents, we previously studied the Chilean native tree Maytenus boaria, isolating four dihydro-β-agarofurans sesquiterpenoids from organic extracts of its seeds [27,28]. However, these compounds were not active in cancer cells models, specifically against MCF-7, PC9, and C4-2B cells (data not shown).…”

A Review on Phytochemicals of the Genus Maytenus and Their Bioactive Studies

“…In addition, bilocularins D–F are the first examples of dihydro-b-agarofurans, which bear a hydroxyacetate group [ 68 , 69 ]. Compounds (1 S ,4 S ,5 S ,6 R ,7 R ,8 R ,9 R ,10 S )-6-acetoxy-4,9,10-trihydroxy-2,2,5 a ,9-tetramethyloctahydro-2 H -3,9 a -methanobenzo[ b ]oxepin-5-yl furan-3-carboxylate ( 2 02 ), (1 S ,4 S ,5 S ,6 R ,7 R ,8 R ,9 R ,10 S )-6-acetoxy-4,9-dihydroxy-2,2,5 a ,9-tetramethyloctahydro-2 H -3,9a-methanobenzo[ b ]oxepine-5,10-diyl bis(furan-3-carboxylate) ( 2 03 ), (1 S ,4 S ,5 S ,6 R ,7 R ,9 S ,10 S )-6-acetoxy-9-hydroxy-2,2,5 a ,9-tetramethyloctahydro-2 H -3,9 a -methanobenzo[ b ]oxepine-5, 10-diyl bis(furan-3-carboxylate) ( 2 04 ) and (1 S ,4 S ,5 S ,6 R ,7 R ,9 S , 10 S )-6-acetoxy-10-(benzoyloxy)-9-hydroxy-2,2,5 a ,9-tetramethyloctahydro-2 H -3,9 a -methanobenzo[ b ]-oxepin-5-yl furan-3-carboxylate ( 2 05 ) were isolated from the seeds of M. boaria [ 70 , 71 ]. Compounds 2 β ,6 β -diacetoxy-1 α ,9 β -dibenzoyl-3 β -hydroxy-dihydro- β -agarofuran ( 206 ), 1 α ,2 α ,6 β ,8 α -tetraacetoxy-9 β -benzoyl-15-hydroxy-dihydro- β -agarofuran ( 207 ) and 1 α ,2 α ,6 β ,8 α ,15-pentaacetoxy-9 β -benzoyl-dihydro- β -agarofuran ( 208 ) have been separated from M. boaria [ 72 ].…”

“…In addition, bilocularins D-F are the first examples of dihydro-b-agarofurans, which bear a hydroxyacetate group [68,69]. Compounds (1S,4S,5S, 6R,7R,8R,9R,10S)-6-acetoxy-4,9,10-trihydroxy-2,2,5a, 9- 205) were isolated from the seeds of M. boaria [70,71]. Compounds 2β,6β-diacetoxy-1α,9β-dibenzoyl-3β-hydroxy-dihydro-β-agarofuran (206), 1α,2α,6β,8α-tetraacetoxy-9β-benzoyl-15-hydroxydihydro-β-agarofuran (207) and 1α,2α,6β,8α,15-pentaacetoxy-9β-benzoyl-dihydro-β-agarofuran (208) have been separated from M. boaria [72].…”