Diversity Oriented Synthesis of Novel Xanthones Reveal Potent Doxorubicin-Inspired Analogs

ChemMedChem. 2024 Feb 13:e202400055. doi: 10.1002/cmdc.202400055. Online ahead of print.ABSTRACTInspired by potent antiproliferative xanthone natural products and so far limited examples of derived bioactive agents, a structure activity study of architecturally novel types of xanthones is reported. Their preparation was enabled in a short and divergent manner by a modular chlorination in combination with optimized protocols for a polar condensation and a hetero-cyclization. Application of these procedures allowed for the synthesis of various polyhalogenated representatives (including mixed bromo/chloro xanthones) that were obtained in up to fourfold improved yields as compared to previous procedures. Subsequent Suzuki coupling of either halide enabled access to phenyl- and chloro-bearing xanthones, which may be functionalized at four out of five non-hydroxylated positions. Antiproliferative assays against breast cancer cell lines revealed potent activities of some of these simplified analogs that are in the range of pharmaceutically used anticancer drug doxorubicin.PMID:38351738 | DOI:10.1002/cmdc.202400055
Source: ChemMedChem - Category: Chemistry Authors: Source Type: research