Discovery and Theoretical Studies of Nonenzymatic Polyketide Dimerizations of Chaetophenols

Nonenzymatic reactions sometimes construct complex structures observed in natural products, showing us unique chemical reactions. In our exploration of natural products, we identified a novel type of isochromene-derived polyketide dimer 7 with a 6/6/6/6/6 five-ring system from Chaetomium indicum along with several new related polyketides. We demonstrated that isochromene 6 and its oxidized derivative 8 undergo nonenzymatic dimerization under acidic conditions to give 7. Furthermore, density functional theory (DFT) calculations revealed the dimerization pathways, suggesting that the acidity (reaction condition) and O-prenylation are key factors in determining reaction mode.