Periodic Reporting for period 3 - TERPENECAT (Bridging the gap between supramolecular chemistry and current synthetic challenges: Developing artificial catalysts for the tail-to-head terpene cyclization)
Reporting period: 2019-11-01 to 2021-04-30
The main objective of the project is to learn how to synthesize terpenes, a very important class of natural products, much more efficiently in the laboratory. To do so, we try to mimic the complex bio-machinery with much simpler catalysts in the laboratory. This may lead to the discovery of new drugs and more resource-friendly production routes.
In WP1.2 we synthesized several novel chiral building blocks which assemble to 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 capsule 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 first examples of optically active terpene cyclization products formed inside the capsule. These results also allowed us to start working on WP2 already.
In WP1.3 one of the two desired building blocks was synthesized already. Interestingly, it seems to assemble differently than anticipated. Work to elucidate its assembled structure and to understand its encapsulation behavior is ongoing.
WP 1.4: This WP was deprioritized due to results from WP1.1. It is not essential for work on WP2 anymore.
1) We identified the prerequisites for catalytic activity of resorcinarene-like catalysts. Since it is the only supramolecular catalyst currently available for tail-to-head terpene cyclization, this was a very important break through.
2) Based on our supramolecular catalysis approach, we developed a very short route (four-steps) to the presilphiperfolanol family of natural products was developed. This is much shorter than the available synthetic routes (13 steps or more). This will enable us to explore a wide range of unnatural derivatives of this biologically interesting class of sesquiterpene natural products.