We are investigating supramolecular host structures for their potential as catalysts. Although a large diversity of supramolecular hosts has been described over the last decades, applications of such hosts as catalytic reaction chambers are still rare. We are interested in a variety of different reactions – for first results see also the list of publications.
One especially fascinating application of such host structures is terpene chemistry. Our research in this direction is inspired by the beauty of terpene biosynthesis. Terpenes constitute the largest and most diverse class of natural products with several tens of thousands of different members. They represent an essential part of drug development programs. Important current drugs like taxol/paclitaxel (cancer treatment) or artemisinin (anti-malaria) have emerged from terpene natural products. Interestingly, the variety of terpene products in nature is formed from only a handful of relatively simple acyclic precursors: geranyl-pyrophosphate (PP) for monoterpenes (10 C-atoms), farnesyl-PP for sesquiterpenes (15 C-atoms) and geranylgeranyl-PP in case of diterpenes (20 C-atoms). These simple precursors are cyclized via complex cationic reaction cascades, termed tail-to-head terpene (THT) cyclizations, into the whole variety of terpene carbon structures. As an example the biosynthesis of taxol is shown here:
These THT cyclizations are considered to be among the most complex chemical reactions occurring in nature. Most of the atoms of the acyclic terpene precursor change their hybridization or bonding during the cationic cyclization cascade. Nature has evolved enzymes termed terpene cylcases or synthases for this task. Man-made catalysts for the THT cyclization are lacking. Learning how to design such complex catalysts will not only enable us to mimic natural enzymes, but to enter uncharted territory of terpene chemistry. To influence the conformation of the flexible acyclic terpenes and to stabilize cationic transition states, enzymes surround the substrate more or less completely. Mimicking such a catalytically active pocket with artificial, non-peptidic catalysts represents a major challenge. Our long term goal is to tackle this challenge by utilizing supramolecular chemistry. First results from our lab are encouraging.
In parallel, we also started working on CH-oxidations since they will be an essential part for the functionalization of the terpene carbon structures. These results have not been published so far.