Work on WP1.1 has been completed. We identified the prerequisites for the catalytic activity of resorcinarene-like catalysts. Water that is part of the supramolecular assembly plays a crucial role in transporting the proton from the solvent onto the encapsulated substrate.
In WP1.2 we synthesized several novel chiral building blocks which assemble into hexameric capsules. Since the separation of the enantiomers proved to be a technical challenge, we explored alternatives. 1) Installation of chiral information at the feet of the resorcinarene. Three optically active capsules were synthesized. Unfortunately, they did not provide optically active cyclization products. However, this study led to the discovery of an interesting effect on the enantioselective iminium catalysis inside the capsule. 2) Attaching chiral information on the leaving group of the terpene substrate. 3) Utilizing easily accessible chiral, cyclic terpenes as cyclization substrates. This study provided very recently the first examples of optically active terpene cyclization products formed inside the capsule. These results also allowed us to start working on WP2 already. Recently, a breakthrough was achieved. We were able to achieve the first enantioselective THT cyclization inside a supramolecular capsule, achieving the main goal of WP1.2.
In WP1.3 a novel building block was synthesized successfully. It assembles to a very large cage-like structure that was investigated closely. However, its properties were not suitable for terpene cyclizations.
WP 1.4: This WP was deprioritized due to results from WP1.1 as it would lead to catalytically inactive capsules. It is not essential for work on WP2.
In WP2 we succeeded in expanding the natural variety of terpenes to access unprecedented derivatives.
In this project, we succeeded in producing complex terpene natural products much more efficiently than any other alternative means available. Even more interestingly, we successfully expanded the natural variety of terpenes to access unprecedented derivatives. One main application of the methodology developed is already published; a four-step synthesis of novel derivatives of the complex sesquiterpene natural product presilphiperfolan-1β-ol, enabled by our supramolecular capsule cyclization methodology. We are currently applying this methodology to further natural products and also potential fragrance compounds.
