Efficient synthesis of frutinone A and its derivatives through palladium-catalyzed C - H activation/carbonylation
Yongje Shin1, Changho Yoo, Youngtaek Moon
1Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701 (Korea); Center for Catalytic Hydrocarbon Functionalization, Institute for Basic Science (IBS), Daejeon, 305-701 (Korea).
Abstract:
Frutinone A, a biologically active ingredient of an antimicrobial herbal extract, demonstrates potent inhibitory activity towards the CYP1A2 enzyme. A three-step total synthesis of frutinone A with an overall yield of 44 % is presented. The construction of the chromone-annelated coumarin core was achieved through palladium-catalyzed CH carbonylation of 2-phenolchromones. The straightforward synthetic route allowed facile substitutions around the frutinone A core and thus rapid exploration of the structure-activity relationship (SAR) profile of the derivatives. The inhibitory activity of the synthesized frutinone A derivatives were determined for CYP1A2, and ten compounds exhibited one-to-two digit nanomolar inhibitory activity towards the CYP1A2 enzyme.
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