Synthetic study on the main tetracyclic core of myrioneurinol

A synthetic study on the formation of the main tetracyclic core of myrioneurinol, an antiplasmodial compound belonging to the myrioneuron alkaloid family, has been completed. This approach begins with a tetralone derivative and emphasizes an oxidative dearomatizing 1,3-alkyl shift process mediated by an environmental-friendly hypervalent iodine reagent as a pivotal step. Other steps include formylation, an SN2-Michael cascade process, oxidative acetalization, and trans-acetalization. To prove the concept of a viable strategy, the key tetracyclic system obtained was transformed into a known myrioneurinol intermediate observed during the synthesis of Prof. Ma and coworkers in 2022. Moreover, this study identified a variety of complex and intriguing polycyclic systems as by-products, demonstrating the synthetic potential of this approach in the rapid formation of compact, functionalized scaffolds.