Total synthesis of polycyclic polyprenylated acylphloroglucinol natural products and derivatives
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.
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