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.