First Total Synthesis of Original Chalcone-Flavone Dimers as Cissampeloflavone Analogues

The total synthesis of furoflavones closely related to the natural product cissampeloflavone was explored following different pathways. The involvement of a flavone as a key intermediate proved to be the most efficient way to form the 7-phenyl-5H-furo[3,2-g]chromen-5-one scaffold, and the first example of furoflavone formation was achieved in this way. For the synthesis of chalcone-flavone dimers, two different strategies were examined: either acylation at the very end of the synthesis, or introduction of the 3-acyl group during furan-ring formation. The final acylation was hardly achievable with hindered benzoyl chlorides, but a simpler 4-methoxybenzoyl group was added to the furoflavone in modest yield. The alternative direct introduction of this acyl group during furan formation proved to be more efficient. Conjugate addition of an iodoflavone to an ynone followed by intramolecular Heck cyclization gave the best results, leading to the first synthetic chalcone-flavone dimer ever described.