Four-Step Access to the Sesquiterpene Natural Product Presilphiperfolan-1β-ol and Unnatural Derivatives via Supramolecular Catalysis

Terpenes constitute one of the most
structurally varied classes
of natural products. A wide range of these structures are produced
in nature by type I terpene cyclase enzymes from one single substrate.
However, such reactivity has proven difficult to reproduce in solution
with man-made systems. Herein we report the shortest synthesis of
the tricyclic sesquiterpene presilphiperfolan-1β-ol to date,
utilizing the supramolecular resorcinarene capsule as catalyst for
the key step. This synthetic approach also allows access to unnatural
derivatives of the natural product, which would not be accessible
through the biosynthetic machinery. Additionally, this study provides
useful insight into the biosynthesis of the presilphiperfolanol natural
products, including the first experimental evidence consistent with
the proposed biosynthetic connection between caryophyllene and the
presilphiperfolanols.