Synthetic studies toward the synthesis of polyprenylated phloroglucinol natural products

An efficient approach to the synthesis of bicyclo[3.3.1]nonane-1, 3, 5-trione core of polyprenylated phloroglucinol natural products has been developed. The key transformation involves a dearomatization-annulation of clusiaphenone B. We have evaluated the scope and limitation of the developed methodology and a number of bicyclo[3.3.1] polyprenylated phloroglucinol derivatives have been prepared. The dearomatization-anulation methodology has been successfully applied to the total synthesis of polyprenylated phloroglucinol natural product (+/-)-clusianone.;An enantioselective variant of alkylative dearomatization process using dimeric chiral phase-transfer catalysts (PTC) has also been developed. The synthesis of a chiral, non-racemic adamantane polyprenylated acylphloroglucinol (PPAP) core structure has been achieved using the enantioselective dearomatization process. The absolute configuration of the major enantiomer of dearomatization product was assigned by X-ray crystal structure analysis. NMR and computational studies were utilized to understand the mechanism of the dearomatization process.;We have developed a retro-aldol/addition process for the syntheses of polyprenylated phloroglucinols with 7-epi stereochemistry. Enantioselective total syntheses and absolute configuration assignment of both 7-epi-clusianone and hyperibone K have been achieved by application of the retro-aldol/addtion process and PTC-catalyzed asymmetric dearomatization process.