Concise synthesis of prenylated and geranylated chalcone natural products by regiospecific iodination and Suzuki coupling reactions

Abstract Four natural chalcones bearing prenyl or geranyl groups, i.e., isobavachalcone ( 1 ), bavachalcone ( 2 ), xanthoangelol ( 3 ), and 2′,4′,4-trihydroxy-5′-geranylchalcone (isoxanthoangelol, 4 ) were synthesized by using a regio-selective iodination and the Suzuki coupling reaction as key steps. Among them, the first total synthesis of 2′,4′,4-trihydroxy-5′-geranylchalcone was achieved in 36% overall yield. Comparing with the reported methods based on C-alkylation or O-alkylation followed by Claisen rearrangement to introduce the side chain, this new strategy capitalizes on a precious regiochemical control during iodination. The overall yields for the synthesis of the first three chalcones were improved from 17% to 53%, 12% to 35%, and 28% to 50%, respectively.