Sesquiterpene cyclizations catalysed inside the resorcinarene capsule and application in the short synthesis of isolongifolene and isolongifolenone

Terpenes constitute the largest class of natural products and serve as an important source for medicinal treatments. Despite constant progress in chemical synthesis, the construction of complex polycyclic sesqui- and diterpene scaffolds remains challenging. However, natural cyclase enzymes are able to form the whole variety of terpene structures from just a handful of linear precursors. Man-made catalysts able to mimic such natural enzymes are lacking. Here, we describe examples of sesquiterpene cyclizations inside an enzyme-mimicking supramolecular catalyst. This strategy allowed the formation of the tricyclic sesquiterpene isolongifolene in only four steps. The mechanism of the catalysed cyclization reaction was elucidated using 13 C-labelling studies and density functional theory calculations.