Total synthesis of polycyclic polyprenylated acylphloroglucinol natural products and derivatives

Thesis (Ph.D.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.An efficient approach to the synthesis ofbicyclo [3.3.1] nonane-1, 3, 5-trione core of polycyclic polyprenylated acylphloroglucinol natural products (PPAPs) has been developed previously in our laboratory. The key transformation involves base-mediated dearomatization-annulation of a fully substituted acyl phloroglucinol. Application of this key transformation has been successful for the total synthesis of type B PPAPs 7-epi-clusianone. Synthesis efforts towards the type A PPAPs, including the adamantane-bearing natural product plukenetione A were evaluated. Initial attempts involved adapting the similar methodology for the previous synthesis of 7-epi-clusianone and this method successfully constructed the target molecules' core framework. Alternative approaches for plukenetione A synthesis were evaluated and a new method involving tandem base-mediated dearomatization and acid catalyzed annulation of acyl phloroglucinol was identified. This key methodology along with modified retro-aldol condensation Grignard addition and stereoselective cyclization led to the successful synthesis of type A adamantane plukenetione A. We have also developed a unified strategy for the synthesis ofthe type A PPAP 7-epi-nemorosone. Beginning with the same adamantane intermediate obtained in the plukenetione A synthesis, the natural product 7-epi-nemorosone was prepared in ten chemical steps. Preliminary evaluation of oxidative cyclizations of 7-epi-nemorosone to produce polycyclic structure has been conducted