Collective Synthesis of Meroterpenoids Derived from Ganoderma Family

For long years, meroterpenoids derived from Ganoderma family have received a great deal of attention due to their unique biological activities. Applanatumol compounds or lucidumone were isolated from G. applanatum or G. lucidum, featuring dihydroquinone motif fused to terpenoid structure. This article describes collective synthesis of applanatumol compounds and asymmetric synthesis of lucidumone. Applanatumol A, having a spiro [benzofranbicyclo[3.2.2]nonane] framework with four stereogenic centers, was synthesized via a tandem cascade cyclization using TBD to form tetracyclic skeleton. Applanatumol B was synthesized in 14 steps by employing an intramolecular cyclization and lactonization for quick construction of the tricyclic skeleton with desired stereochemistry. The key step includes efficient epimerization of α-position of the ketone under acidic condition. Lucidumone is a unique 6/5/6/6/5 polycyclic molecule with six contiguous stereogenic centers on a bicyclo[2.2.2]octane skeleton. The racemic total synthesis was accomplished in 10 steps through one-pot preparation of the tetracyclic core framework by Claisen rearrangement followed by an intramolecular aldol reaction. The intramolecular aldol reaction allowed for the stereocontrolled construction of the bicyclo[2.2.2]octane skeleton fused to an indanone structure. The enantioselective total synthesis of lucidumone was also described via a chiral transfer strategy in the Claisen rearrangement. Our work communicated here provides novel strategy for convenient and short-step synthesis of meroterpenoids using tandem reaction or one-pot reaction.