title: Efficient synthesis of frutinone A and its derivatives through palladium-catalyzed C - H activation/carbonylation.
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 CH 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.
authors.affiliation: Department 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).
authors.forename: Yongje
authors.initials: Y
authors.lastname: Shin
authors.forename: Changho
authors.initials: C
authors.lastname: Yoo
authors.forename: Youngtaek
authors.initials: Y
authors.lastname: Moon
authors.forename: Yunho
authors.initials: Y
authors.lastname: Lee
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Hong
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D002867:Chromones / Q000138:chemical synthesis* / Q000737:chemistry; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry; D019388:Cytochrome P-450 CYP1A2 / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D002867:Chromones; D003374:Coumarins; C581826:frutinone A; D010165:Palladium; D019388:Cytochrome P-450 CYP1A2
keywords: CH functionalization; carbonylation; frutinone A; palladium; structure-activity relationships