No abstract

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.

Studies of recent environmental perturbations often rely on data derived from marine sedimentary records. These records are known to imperfectly inscribe the true sequence of events, yet there is large uncertainty regarding the corrections that should be employed to accurately describe the sedimentary history. Here we show in recent records from the Gulf of Aqaba, Red Sea, how events of the abrupt disappearance of the planktonic foraminifer Globigerinoides sacculifer, and episodic deposition of the artificial radionuclide 137 Cs, are significantly altered in the sedimentary record compared to their known past timing. Instead of the abrupt disappearance of the foraminifera, we observe a prolonged decline beginning at core depth equivalent to ~30 y prior to its actual disappearance and continuing for decades past the event. We further observe asymmetric smoothing of the radionuclide peak. Utilization of advection-diffusion-reaction models to reconstruct the original fluxes based on the known absolute timing of the events reveal that it is imperative to use a continuous function to describe bioturbation. Discretization of bioturbation into mixed and unmixed layers significantly shifts the location of the modeled event. When bioturbation is described as a continuously decreasing function of depth, the peak of a very short term event smears asymmetrically but remains in the right depth. When sudden events repeat while the first spike is still mixed with the upper sediment layer, bioturbation unifies adjacent peaks. The united peak appears at an intermediate depth that does not necessarily correlate with the timing of the individual events. In a third case, a long lasting sedimentary event affected by bioturbation, the resulting peak is rather weak compared to the actual event and appears deeper in the sediment column than expected based on the termination of the event. The model clearly shows that abrupt changes can only endure in the record if a thick sediment layer settled on the sediment-water interface at once or if bioturbation rates decreased to very low values for a prolonged period of time. In any other case smearing by bioturbation makes an abrupt event appear to have started shortly before the real timing and end long after its true termination.

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.

Terpene and terpenoid syntheses are challenging tasks because of the required multiple synthetic steps, exact functionalization, and difficult purification that reduce the yields. One of the propitious methods to tackle this problem is the synthesis of terpenes inside nanocapsules. Nanocapsules based on resorcinarene moieties have recently been employed experimentally to generate sesquiterpenes, but the improvement of product distribution control in such nanoreactors is currently challenging due to a lack of specificity. In the current work, we study the in-capsule reactions employing multiscale modeling techniques along with a high-temperature Langevin molecular dynamics simulation protocol as well as the potential of mean force using the umbrella sampling technique. Additionally, we generate a sesquiterpene database with information derived from quantum chemical calculations. Using these methods, we shed light on thermodynamics, kinetics, product selectivity, and the chemical mechanism of sesquiterpene formation inside the resorcinarene-based nanocapsule. We find that, although the capsule produces many of the most stable known sesquiterpenes, several very stable sesquiterpenes are not formed. We ascribe this to reaction mechanisms involving intrinsically high energy secondary cations, which are avoided, even in the capsule. The current reaction modeling approach is expected to aid in the design of synthetic strategies for in-capsule sesquiterpene production.