Caged xanthone derivatives to promote mitochondria-mediated apoptosis in breast cancer cells.

Caged xanthones represent a class of natural secondary metabolites exhibiting significant potential as antitumor agents. These compounds are characterized by their distinct cage-like structures, which offer novel and compelling frameworks for drug design. Nonetheless, there exists a dearth of research focused on the structural modification of these compounds, particularly in relation to their cage-like architectures. This study aims to address this gap by introducing an innovative synthetic method for constructing a novel caged structure that incorporates a widely employed maleimide group. Drawing upon the well-established synthetic approach for dihydroxanthones previously developed within our research group, we successfully synthesized 13 new caged xanthones using the Diels-Alder reaction. Subsequently, we evaluated their anti-proliferative activity against HepG2, A549, and MDA-MB-231 cell lines. The results revealed that compound 10i exhibited IC50 values of 15.86 µM ± 1.29, 19.27 µM ± 1.58, and 12.96 µM ± 0.09 against these cell lines, respectively. Further investigations into the mechanism of action of 10i demonstrated its ability to induce G2/M cell cycle arrest and initiate mitochondria-mediated apoptosis in breast cancer cells.

Sequential Dieckmann cyclization enables the total synthesis of 7-epi-clusianone and 18-hydroxy-7-epi-clusianone.

A unified approach for the construction of the bicyclo[3.3.1]nonane-2,4,9-trione core of polycyclic polyprenylated acylphloroglucinols (PPAPs) was reported. This approach involves a sequential process of two distinct Dieckmann condensation reactions from the linear precursor. Using this method, the divergent total synthesis of the natural products 7-epi-clusianone and 18-hydroxy-7-epi-clusianone and the formal synthesis of sampsonione P were achieved. Additionally, other key steps to realize this strategy include RuCl3-catalyzed oxidative olefin cleavage and Pd-catalyzed Tsuji-Trost decarboxylative allylation. The synthesis indicated that bicyclo[3.3.1]nonane-2,4,9-triones could also be constructed via 6-membered intermediates.

Xanthone Glucosides: Isolation, Bioactivity and Synthesis.

Xanthones are secondary metabolites found in plants, fungi, lichens, and bacteria from a variety of families and genera, with the majority found in the Gentianaceae, Polygalaceae, and Clusiaceae. They have a diverse range of bioactivities, including anti-oxidant, anti-bacterial, anti-malarial, anti-tuberculosis, and cytotoxic properties. Xanthone glucosides are a significant branch of xanthones. After glycosylation, xanthones may have improved characteristics (such as solubility and pharmacological activity). Currently, no critical review of xanthone glucosides has been published. A literature survey including reports of naturally occurring xanthone glucosides is included in this review. The isolation, structure, bioactivity, and synthesis of these compounds were all explored in depth.

An efficient approach for the synthesis of 1,2-dihydroxanthones enabled by one-pot Claisen condensation/cyclization reactions.

1,2-Dihydroxanthones (DHXs) are core structures of natural products and useful building blocks in organic synthesis. So far, they have been less studied. In this report, a mild, efficient and green method for the synthesis of 1,2-dihydroxanthones has been developed in one pot through Claisen condensation and O-cyclization under waste-induced relay catalysis with minimum organic solvents. The by-product (HMDS or NH3·H2O) of the first step turned out to be the promoter for the second step, which could efficiently proceed in aqueous media without the addition of other catalysts. The reactions using trifluoroethyl salicylates could be performed under mild conditions to ensure the generation of vulnerable DHXs in high yields. The substrate scope is very broad regardless of the substituent type and its position on the structure. Specifically, the versatility of DHXs was demonstrated by their conversion to xanthones and other complex structures.