The elansolids: how nature shows chemists how to tamep-quinone methides

Covering: up to 2025Elansolids are metabolites isolated from the gliding bacterium Chitinophaga sancti (formerly Flexibacter spec.). The fascinating structures of this type of natural products, as well as their promising biological antibiotic activities, have triggered considerable efforts in the study of elansolids, especially their biosynthesis, which features the formation of highly reactive p-quinone methide intermediates in the enzymatic dehydration-IMDA process. This review focuses on the various aspects of p-quinone methides, including their formation, reactivities (chemical transformations), and applications in total synthesis, all of which are elucidated based on the example of elansolids. By highlighting this particular instance of p-quinone methides, it is shown how nature, namely, the enzymes in the PKS assembly line, could tame this type of highly reactive intermediate. Furthermore, by mimicking the p-quinone methide-mediated IMDA process as observed in biosynthesis, chemists can rationally access various synthetically challenging intermediates, for instance tetrahydroindanes, and utilize them in the total synthesis of the elansolid family.