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, but 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 direct experimental evidence for the proposed biosynthetic connection between caryophyllene and the presilphiperfolanols.

We used microfabricated cantilever array sensors for an artificial nose setup. Each cantilever is coated on its top surface with a polymer layer. Volatile gaseous analytes are detected by tracking the diffusion process of the molecules into the polymer layers, resulting in swelling of the polymer layers and therewith bending of the cantilevers. From the bending pattern of all cantilevers in the array, a characteristic 'fingerprint' of the analyte is obtained, which is evaluated using principal component analysis. In a flow of dry nitrogen gas, the bending of the cantilevers is reverted to its initial state before exposure to the analyte, which allows reversible and reproducible operation of the sensor. We show examples of detection of solvents, perfume essences and beverage flavors. In a medical application, the setup provides indication of presence of diseases in patient's breath samples.

Nature uses templated length-controlled oligomerization to process genetic information. Templates that are DNA and RNA based and fully synthetic have also been developed for preparing unnatural oligomers. However, these reactions require stoichiometric amounts of the template for product formation. Here we report a catalytic macrocyclic template that promotes the oligomerization of a small-molecule substrate with a remarkable degree of length control. The design of the template is based on rigid oligoproline moieties decorated with catalytic sites in a defined spatial arrangement. The dimension of the macrocycle and the number of catalytic moieties determine the number of monomers that are incorporated into the growing oligomer, thus allowing access to specific products with lengths preprogrammed by the template.

Terpenes represent the largest and the most diverse class of natural compounds. This is remarkable as the whole variety is accessed from just a handful of highly conserved linear precursors. Modification of the cyclization precursors would enable a dramatic expansion of the accessible chemical space. However, natural enzymes do not enable us to tap into this potential, as they do not tolerate larger deviations from the prototypical substrate structure. Herein we report that supramolecular capsule catalysis enables facile access to diverse and novel terpenoid skeletons that formally can be traced back to C3-phenyl, benzyl, and homoprenyl derivatives of farnesol. Novel skeletons related to the presilphiperfolane core structure, as well as novel neoclovene derivatives were accessed efficiently in only four synthetic steps. Importantly, the products obtained carry functional groups that may be readily derivatized further.

Terpene stellen die größte und vielfältigste Klasse von Naturstoffen dar. Dies ist bemerkenswert, da die gesamte Vielfalt aus nur einer Handvoll hoch konservierter linearer Vorstufen zugänglich ist. Eine Modifizierung der Zyklisierungsvorstufen würde eine dramatische Erweiterung des zugänglichen chemischen Raums ermöglichen. Natürliche Enzyme ermöglichen es uns jedoch nicht, dieses Potenzial zu nutzen, da sie keine größeren Abweichungen von der prototypischen Substratstruktur tolerieren. Hier berichten wir, dass die supramolekulare Kapselkatalyse einen einfachen Zugang zu verschiedenen und neuartigen Terpenoidgerüsten ermöglicht, die formal auf C3-Phenyl-, Benzyl-und Homoprenylderivate von Farnesol zurückgeführt werden können. Neuartige Gerüste, die mit der Presilphiperfolan-Kernstruktur verwandt sind, sowie neuartige Neoclovenderivate wurden in nur vier Syntheseschritten effizient zugänglich gemacht. Wichtig ist, dass die erhaltenen Produkte funktionelle Gruppen tragen, die leicht weiter derivatisiert werden können. Die erzielten Ergebnisse zeigen das Potenzial der supramolekularen Katalyse für die Erschließung des riesigen chemischen Raums der Terpenoide, der von der Natur noch nicht genutzt wurde.