Syntheses of Dimeric Tetrahydroxanthones with Varied Linkages: Investigation of “Shapeshifting” Properties

The 2,4′- and 4,4′-linked variants of the cytotoxic agent secalonic acid A and their analogues have been synthesized. Kinetic resolution of an unprotected tetrahydroxanthone scaffold followed by copper-mediated biaryl coupling allowed for efficient access to these compounds. Evaluation of the “shapeshifting” properties of 2,2′-, 2,4′-, and 4,4′-linked variants of the secalonic acids A in a polar solvent in conjunction with assays of the compounds against select cancer cell lines was conducted to study possible correlations between linkage variation and cytotoxicity.