Total synthesis of cyclodepsipeptide sunshinamide has been achieved for the first time using a convergent approach. The key features of this synthesis comprise Crimmins acetate aldol, Shiina esterification, amide coupling, macrolactamization, and an I 2 -mediated deprotection with concomitant disulfide-bridge formation. This synthetic study enabled the unambiguous determination of the stereochemistry of the unassigned stereocenter of the isolated sunshinamide. The cytotoxicity of sunshinamide and one of its analogues was evaluated against different cancerous and noncancerous human cell lines, which revealed their attractive and selective activities toward cancer cells at very low concentrations.

Cananginones, a family of linear acetogenins found as secondary metabolites in the plant kingdom, show cytotoxicity against several types of cancer cells. We aimed to investigate the efficacy of cananginone and its mechanism as an anti-cancer agent. Our initial screening of Cananginone against HepG2, PC3, A549, and MCF7 cells showed anti-cancer activities and is more potent against MCF7 cells, consistent with the previous report. Next, cell-based assays have revealed that cananginone abrogates cancer stem cell renewal as well as Epithelial-Mesenchymal Transition (EMT) and increased the ROS level beyond the threshold level thus reducing the viability of cancer cells. In the connection of Hh-Gli to EMT, our study indicated that cananginone inhibits Gli1 in a noncanonical pathway. Presumably, this is the first report on the inhibitory activity of cananginone in the Hh pathway and is different from Hh-antagonists cyclopamine and GANT 61 considering the mechanism.

Stereoselective total synthesis of structurally intriguing polyketide natural product thailandamide lactone has been accomplished for the first time adopting a convergent approach. The key feature of this synthesis includes Crimmins...

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