Strategies towards endo-type B polycyclic polyprenylated acylphloroglucinols: total synthesis of regio-hyperibone L and (+)-epi-clusianone

A concise and stereoselective method toward the divergent synthesis of polycyclic polyprenylated acylphloroglucinols and the analogues in both racemic and asymmetric fashions was developed. With the bioinspired Me2AlSEt-promoted domino Dieckmann cyclization as the key strategy, the total synthesis of regio-hyperibone L and the first asymmetric total synthesis of natural epi-clusianone were achieved, which determined the absolute configuration of epi-clusianone and demonstrated the broad synthetic applicability of the domino method. Furthermore, by a stereoselective alkylation/reductive deprotection/cyclization strategy, the key enantioenriched 5-substituted lactones for accessing epi-clusianone are prepared efficiently, which provides a general asymmetric approach towards the synthesis of endo-type B PPAPs.

Automated summary

A concise and stereoselective method has been developed for the synthesis of polycyclic polyprenylated acylphloroglucinols and analogues in both racemic and asymmetric fashions. This method has been successfully applied in the total synthesis of natural products with biological activities.