Synthesis and Biological Evaluation of ABCD Ring Fragments of the Kibdelones

Abstract

Arylierungen jetzt auch mit Platin: Die Synthese des Titelsystems gelang durch eine neuartige PtIV‐katalysierte Arylierung eines Chinonmonoketals und anschließende Photocyclisierung (siehe Schema). Nach ersten biologischen Tests an Krebszelllinien sind die verkürzten Kibdelon‐Analoga rund 2000‐mal weniger aktiv als die Kibdelone B und C, was darauf hinweist, dass die Tetrahydroxanthonstruktur der Kibdelone entscheidend für die Zytotoxizität ist.

Dehydrogenative Coupling to Enable the Enantioselective Total Synthesis of (−)‐Simaomicin α

“…[5] Our work builds on the discoveries from the Kelly group, which reported the first synthesis of a polycyclic xanthone natural product, cervinomycin A 2 . [6] Subsequently the Suzuki group disclosed a synthesis of the FD-594 aglycon, [7] and Porco and co-workers [8] and our group [9] independently synthesized kibdelone C (Scheme 1, top). The latter studies were the first to target members of this class that feature a tetrahydroxanthone ring system with its attendant stereogenic centers.…”

“…For example, Pd-mediated couplings of an aryl iodide with an aryl CÀH bond was successful for both kibdelone C [9] and FD-594 aglycon, [7] whereas the Porco synthesis introduced a novel Pt-catalyzed addition of a phenol to a quinone monoacetal. [8] Herein we present an advance in the synthesis of polycyclic xanthone natural products that involves a Pd-mediated direct dehydrogenative coupling of two unfunctionalized aryl rings to forge the key B-D biaryl linkage. This transformation enabled the enantioselective synthesis of simaomicin a and the assignment of its absolute stereochemistry.Our synthetic strategy (Scheme 1, bottom) envisioned assembling the AB-ring isoquinolinone and the DEF tetrahyroxanthone subunits from simpler precursors.…”