Tetrahydroxanthones by sequential Pd-catalyzed C-O and C-C bond construction and use in the identification of the "antiausterity" pharmacophore of the kigamicins.
Readily available C-acylated cycloalkanones undergo efficient Pd catalyzed ring closure/cross-coupling providing 7-substituted tetrahydroxanthones in a single operation. One of the synthesized derivatives (depicted) is shown to selectively kill pancreatic cancer (PANC-1) cells under conditions of nutrient deprivation indicating that the tetrahydroxanthone is responsible, in part, for the "antiausterity" effects of the naturally occurring kigamicins.
Department of Chemistry, University of Warwick, Coventry, United Kingdom.
Penelope A
PA
Turner
Ellanna M
EM
Griffin
Jacqueline L
JL
Whatmore
Michael
M
Shipman
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D010080:Oxazoles; D044004:Xanthones; C484114:kigamicin C; D010165:Palladium; D004317:Doxorubicin