I. Model studies on the formation of the dibenzofuranoquinone core of popolohuanone E. II. Diene precursors for decalin synthesis

Popolohuanone E, isolated from the Pohnpei marine sponge Dysidea sp., exhibits selective cytotoxicity towards human non-small cell lung cancer cells due to potent topoisomerase-II inhibitor activity. It possesses an unusual perhydroxylated benzofuranoquinone core that is believed to have been formed via an oxidative dimerization of cis-fused decalin substituted arenols. Our research focus has been twofold: (i) utilize the molecular symmetry to devise an oxidative dimerization pathway to the unusual aromatic system and (ii) employ the intramolecular Diels-Alder (IMDA) reaction to synthesize the decalin fragments in a stereocontrolled fashion.; The hydroxyquinone precursor, A, for the formation of the dibenzofuran-1,4-dione core was prepared using a Suzuki protocol for biaryl systems. The conditions for the formation of the sensitive aryl anions, the choice of borating agent and the selection of protecting groups for this protocol are discussed.*; The acid catalyzed cyclization of hydroxyquinone A provided several dimeric quinone products that were derived from complex electron transfer processes. Possible mechanisms for the formation of these dimeric products are discussed. Modifications of the protocol that led to new monomeric dibenzofurans were examined and several examples utilizing the process are provided.; To investigate an IMDA cyclization approach to popolohuanone E, a synthesis of dienes with the stereochemical features required for the decalin core, including the syn-dimethyl arrangement, needed to be developed. The oxidation of silyl enol ethers derived from the stereo controlled addition of copper reagents to substituted cyclopentenones gave respectable yields of the desired α-hydroxy ketones. Cleavage of these systems with lead tetraacetate and homologation with Yamamoto's allyl phosphine oxide reagent provided an efficient synthesis of the stereochemically-defined dienes. These systems could prove to be useful partners for an IMDA approach to the decalin core of clerodane systems.; *Please refer to dissertation for diagrams.