Total Synthesis of Lophirone F Hexamethyl Ether.

A practical and efficient approach for the total synthesis of the (±)‐lophirone F hexamethyl ether was reported. The compound was synthesized in 8 steps with a 14.6 % overall yield. The key features of this synthesis are the stereoselective synthesis of a 2,5‐diaryl‐3,4‐disubstituted tetrahydrofuran skeleton via a sequence of [3+2] cycloaddition/Krapcho decarboxylation and the installation of two aryl ketone groups bypassing potential epimerization of adjacent stereocenters. Lophirone F, a hexaphenolic biflavonoid natural product, shows inhibitory activities against tumor promoter. A new route (8 steps) to the natural product derivative lophirone F hexamethyl ether was developed. Key steps involve the [3+2] cycloaddition of donor–acceptor cyclopropane with aldehyde to construct the tetrahydrofuran core of the natural product. The route is flexible and would be amenable to the synthesis of analogues of this class of natural products. [ABSTRACT FROM AUTHOR]