Search

(1, Scheme 1), the prototypical member of astructurally related family of antibiotics known as therubromycins, consists of a densely oxygenated naphthazarinring and an isocoumarin moiety linked through a uniquearomatic 5,6-spiroketal ring system (Scheme 1). The rubro-mycins exhibit a wide range of biological activity includingantimicrobialandanticancerproperties.

Studies toward the synthesis of three biologically active (5,6)-benzannulated spiroketal natural products are described. The first total synthesis of paecilospirone is reported, employing a late-stage, pH-neutral spiroketalization. A formal synthesis of γ-rubromycin is described, where the spiroketal moiety is formed by delicate manipulation of the electronic properties of the spirocyclization precursor. Finally, model work toward the total synthesis of berkelic acid is summarized, introducing a novel Horner-Wadsworth-Emmons/oxa-Michael (HWE/oxa-M) cascade to access the spiroketal precursor.

Covering: up to late 2009 A review of the isolation, biological activity and synthesis of natural products containing a benzannulated spiroketal moiety is provided.

The synthesis of a series of 6,6-bisbenzannulated spiroketals using a novel microwave-assisted DIHMA approach is reported. Coupling of an aryl acetylene and an aryl aldehyde via acetylide anion addition resulted in the formation of an alkynol which was followed by oxidation to the desired ynone. Spirocyclization using the DIHMA protocol afforded the desired bisbenzannulated spiroketal in good yield.