The phyllanthusmins are a class of arylnaphthalene lignans isolated from the <i>Phyllanthus poilanei</i> species by the Kinghorn lab in 2014. This series of compounds is composed of a glycoside - typically arabinose attached to the diphyllin aglycone - and possesses potent cytotoxic activity against several cancer cell lines including HT-29. Despite a strong structural resemblance to etoposide, a known topoisomerase II inhibitor, the phyllanthusmins have been shown to exert their cytotoxic effects through alternative mechanisms. Several structural analogues have been synthesized in our lab and evaluated for biological activity resulting in more potent derivatives. In an attempt to improve the physicochemical properties of the analogues, while maintaining activity, late stage functionalization to the diphyllin core through direct C-H activation is currently under exploration. These changes are anticipated to modulate the potency, solubility and metabolism of the analogues. The development of these methods in this highly collaborative project will be highlighted.

C-H functionalization of phyllanthusmin natural products: Rapid generation of a library of anticancer agents

251st National Meeting (2016)

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